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Aging

Episodes

Posted on January 21st 2025 (4 months)

In this clip, Dr. Rhonda Patrick discusses sauna benefits, VO2 max, HIIT, sulforaphane, and strategies to enhance cardiovascular health and longevity.

Posted on January 21st 2025 (4 months)

In this clip, Dr. Rhonda Patrick explores the causes of gray hair, its prevention, and potential remedies like exercise, supplements, and red light therapy.

Posted on June 27th 2024 (11 months)

In this episode, we’re taking a deep dive into alcohol. We’ll explore the science, misconceptions, controversies, and health effects of this widely used drug.

Topic Pages

  • Aerobic exercise

    Aerobic exercise, physical activity that increases breathing and heart rate, promotes cardiovascular, brain, and whole-body health.

  • Age-related decline of muscle power (powerpenia)

    Muscle power is the ability to generate force quickly and is a biomarker of healthy aging.

  • Autophagy

    Autophagy, or “self-eating,” is a response to stress in which a cell destroys damaged or dysfunctional components in order to adapt to external conditions.

  • Berberine

    Berberine is a plant-based compound with pharmacological actions that share many features with metformin.

  • Beta-hydroxybutyrate

    Beta-hydroxybutyrate is a ketone body and source of cellular energy produced via the breakdown of fats during carbohydrate scarcity and fasting.

  • Caloric restriction

    Caloric restriction is the practice of long-term reduced energy intake. It delays the onset of age-related chronic diseases in animals.

  • Creatine

    Creatine is a naturally occurring compound best known for its widespread use as a dietary supplement to enhance physical performance.

  • Epigenetic aging clocks

    Epigenetic clocks are predictors of biological age based on alterations in an individual's DNA methylation profile.

  • Fasting

    Fasting – the voluntary abstinence from food and drink – is an ancient practice now widely appreciated for its beneficial effects on healthspan.

  • FOXO

    FOXO proteins are transcriptional regulators that play an important role in healthy aging. Some FOXO genes may increase lifespan.

  • Hallmarks of aging

    The hallmarks of aging are observable biological patterns of dysfunction that accrue in a biological organism over time.

  • Hydrolyzed collagen

    Hydrolyzed collagen, a mixture of peptides derived from collagen, may improve skin aging, decrease arthritis-induced pain, increase bone mineral density, and reduce hypertension.

  • Metformin

    Metformin, a drug commonly used to treat type 2 diabetes, may modulate certain aging processes.

  • NAD+

    NAD+ is a cofactor that plays an essential role in metabolism, DNA repair, and immunity. Its depletion accelerates aging.

  • Nicotinamide mononucleotide

    Nicotinamide mononucleotide is a precursor of NAD+, a coenzyme necessary for cellular energy production and DNA repair. It is available as a supplement.

  • Nicotinamide riboside

    Nicotinamide riboside is a precursor of NAD+, a coenzyme necessary for energy production and cellular repair. It is available from food and supplements.

  • Omega-3 fatty acids

    Omega-3 fatty acids play critical roles in human health and may be beneficial in ameliorating symptoms associated with chronic health conditions and in combating aging-related diseases.

  • Quercetin

    Quercetin is a plant-based bioactive compound that exerts antioxidant, anti-inflammatory, and anti-aging properties across multiple organ systems.

  • Rapamycin

    Rapamycin, a drug used to treat some cancers and prevent organ rejection, may slow the effects of aging.

  • Salmon roe

    Salmon roe, the internal egg mass found in female salmon, is rich in protein, vitamins, and the omega-3 fatty acids EPA and DHA.

  • Sauna

    Sauna use exposes the body to extreme heat and, in turn, induces protective responses that improve health and may increase healthspan.

  • Senescence

    Senescence is a response to stress in which damaged cells terminate normal growth cycles to prevent dysfunctional cells from reproducing.

  • Sirtuins

    Sirtuins play a key role in healthspan and longevity by regulating a variety of metabolic processes implicated in aging.

  • Toll-like receptors

    Toll-like receptors are a family of pattern recognition receptors expressed on the surface of immune and other cells that play an important role in intestinal permeability and inflammaging.

  • Vitamin D

    Vitamin D is a hormone that plays critical roles in many physiological processes, such as blood pressure regulation, immune function, and cell growth.

News & Publications

  • Scientists have speculated that regular heat exposure, such as that experienced in a sauna, might help aging muscles adapt in ways that preserve strength and mass. A recent study found that older adults who engaged in infrared sauna sessions regularly experienced a 33% increase in the number of small blood vessels surrounding their muscle fibers.

    Researchers asked 14 healthy older adults (65 to 85 years old) to sit in an infrared sauna (60°C, 140°F) for 45 minutes, three times weekly, for eight weeks. They collected muscle biopsies before and after the heat exposure to measure capillarization—the number of capillaries around each muscle fiber—as well as muscle size. They also tracked muscle protein synthesis using amino acid infusions and ultrasound imaging to assess how well blood flowed through muscle tissue after eating. Finally, they measured leg strength using a one-repetition maximum test.

    After eight weeks of heat therapy, participants had 31% to 33% more capillaries surrounding both type I and type II muscle fibers. However, muscle blood flow, protein synthesis rates, leg strength, and muscle size did not improve. Body weight, body composition, and walking speed also stayed the same. The only physical performance measure that improved was handgrip strength, which increased slightly. Interestingly, systolic blood pressure dropped by 2%, while diastolic pressure and resting heart rate were unchanged.

    These findings suggest that passive heat treatment can increase blood vessel density in older muscle tissue, but this change alone doesn’t improve nutrient delivery, muscle building, or strength. Heat exposure might support muscle health in other ways, but it doesn’t appear to be a replacement for resistance or aerobic exercise. Learn more about the benefits of heat exposure in Aliquot #96: Thermal Stress, Part I: The Science Behind Heat Stress and its Positive Effects on Health.

  • Resistance training is a powerful tool for improving the health and well-being of older adults, but many guidelines focus on higher training volumes that may be difficult for some to achieve or maintain. A recent study found that once-weekly, low-volume resistance training boosted physical functioning, energy, and social engagement in older adults, reducing pain by up to 40% and improving strength by 30%.

    Researchers assigned 31 older adults (average age, 66) to one of four groups. Participants trained once a week for six weeks, doing leg press exercises with either a slower, controlled pace or a more explosive effort and using lighter or heavier weekly exercise “doses” (either three or five sets of five repetitions). The researchers assessed the participants' quality of life, functional capacity, strength, and body mass at baseline and weeks 3 and 6.

    They found that participants moved more easily, felt more energetic, and reported less pain after the intervention. Their balance and strength improved, and many participants reported more frequent physical activity—an average increase of 25%—and a 20% improvement in mental health. Most participants (85%) continued exercising after the study, and 95% said they would recommend the program. Many valued the structure and support, with 75% finding the shorter three-by-five routine practical and sustainable.

    These findings suggest that lower-dose, once-weekly resistance training interventions can produce meaningful health improvements in older adults. One of the principal benefits of resistance training is building muscle, which is critical for maintaining health during aging. Learn how it’s never too late to start building muscle in this clip featuring Dr. Rhonda Patrick.

  • As people age, sleeping problems become more common, often affecting mood, memory, and overall health. A recent study found that resistance training improves sleep in older adults better than other forms of exercise.

    Researchers analyzed 25 clinical trials involving more than 2,100 people to see how different kinds of physical activity influenced sleep quality. They looked specifically at the Pittsburgh Sleep Quality Index, a subjective measure of a person’s sleep quality. The studies compared people who exercised to those who adhered to their usual routines, received health education, or did no physical activity at all.

    Strength training was the most effective approach for improving sleep scores, followed by aerobic activity and then a combination of both. People who engaged in strength exercises were more likely to report better sleep, with the strongest improvement observed across all comparisons. Aerobic activity also helped but wasn’t as effective, and combined exercise had a more modest benefit.

    These findings suggest that resistance training does more than build muscle—it also improves sleep. Resistance training builds bone, too, a critical component of aging well. Learn more in this clip featuring Dr. Brad Schoenfeld.

  • Even if you work out, spending most of your day sitting may still adversely affect your health in ways that don’t become apparent until later in life. A recent study found that 35-year-olds who engaged in 30 minutes of vigorous exercise each day had cholesterol levels comparable to those of sedentary 30-year-olds, suggesting that vigorous exercise can offset up to five years of age-related decline in heart health.

    Researchers analyzed data from adults aged 28 to 49 who participated in the Colorado Adoption/Twin Study of Lifespan Behavioral Development and Cognitive Aging. They tracked the time participants spent sitting each day and how often they engaged in moderate or vigorous physical activity. To isolate the effects of behavior from shared genetics and environment, the researchers also compared identical twins with differing activity and sitting patterns. They examined two key health markers: body mass index and the ratio of total to high-density lipoprotein cholesterol—a strong predictor of heart disease risk.

    They found that people who spent more time sitting tended to have higher body mass index and worse cholesterol ratios as they aged. However, among those who sat for the same amount of time—about four hours daily—participants who exercised vigorously for at least 30 minutes daily had cholesterol profiles that resembled those of people five years younger. In some cases, vigorous activity was associated with health markers typical of people up to 10 years younger, but the protective effect weakened with longer sitting durations. In other words, exercise helped—but only to a point.

    These findings suggest that while vigorous exercise offers clear benefits, reducing sitting time is just as important for maintaining good health. “Exercise snacks” can offset the harmful effects of prolonged sitting. Learn more in this clip featuring Dr. Rhonda Patrick and Brady Holmer.

  • While genes play a role in aging, lifestyle and environmental exposures—collectively called the exposome—may have a more robust effect on aging and longevity. A recent study found that the exposome contributes far more to premature death and age-related diseases than genetic risk alone.

    Researchers analyzed data from nearly 500,000 people enrolled in the UK Biobank to measure the exposome’s role in aging. They identified environmental exposures linked to early death and biological aging, then used a proteomic age clock—a tool that tracks molecular signs of aging—to confirm which exposures accelerate the aging process. Finally, they compared the exposome’s influence on disease risk to that of genetic predisposition.

    The exposome explained 17 percentage points more of the variation in mortality than genetic risk, which accounted for less than two percentage points. It was more strongly connected to lung, heart, and liver diseases, while genetic factors were more closely associated with certain cancers and dementias. The analysis identified three disease states and 22 biomarkers related to liver and kidney function, cardiovascular and metabolic health, inflammation, longevity, genetics, and vitamin and mineral status that independently drive biological aging and disease risk.

    These findings suggest that the exposome is critical in shaping health and longevity. While genes contribute to some diseases, environmental exposures throughout life greatly influence aging and survival. Air pollution is an exposome element contributing to disease and early death. Learn how wearable devices measure the air pollution exposome in this episode featuring Dr. Michael Snyder.

  • With more than 80% of older adults in the U.S. having at least one chronic health condition, finding ways to support healthy aging has become a public health priority. A recent study found that people who followed healthy diets over the long term were more than twice as likely to age well—physically, mentally, and emotionally—even into their mid-70s.

    Researchers followed adults for 30 years as part of two large, long-running health studies in the U.S. They looked at how closely people followed eight well-known dietary patterns, including the Alternative Healthy Eating Index (AHEI)—a scoring system that reflects how well someone’s diet aligns with current nutrition guidelines. Other patterns included the Mediterranean diet, the DASH diet, a plant-based diet, and the Planetary Health Diet.

    The researchers also examined diets linked to higher levels of inflammation and insulin resistance and the amount of ultra-processed food people ate. They then compared these patterns to a comprehensive measure of healthy aging, including physical function, cognitive ability, mental health, and freedom from major chronic disease.

    They found that people with the highest AHEI scores were 2.43 times more likely to maintain good overall health as they aged, up to 75. Similar benefits appeared for people who followed Mediterranean-style, MIND, and plant-based diets. In contrast, those who ate the most ultra-processed food or followed dietary patterns that drive inflammation and high blood glucose levels were less likely to age in good health.

    These findings suggest that long-term dietary choices can meaningfully influence how well we age—not just how long we live. Learn more about lifestyle factors that prolong healthy aging in this episode featuring Dr. Rhonda Patrick.

  • Your brain may be aging faster than the rest of your body. While some people maintain brain health well into old age, others experience structural decline much earlier. A recent study found that multiple health factors—including hypertension, diabetes, smoking, and low educational attainment—may speed up brain aging, increasing the risk of cognitive decline and neurodegenerative diseases.

    Researchers analyzed brain scans and long-term health data from 964 adults in northern China, monitoring them for 16 years. They used machine learning to estimate brain age based on imaging techniques and compared brain aging among groups with various high-risk health factors. They also focused on people with high blood pressure to see how it affects brain structure.

    They found that people with four or five high-risk factors had considerably older-looking brains than those with fewer risks, suggesting that multiple health problems may accelerate brain aging. Hypertension, high blood sugar, elevated creatinine (a feature of metabolic disease), smoking, and lower education were the strongest predictors of brain structure decline. However, hypertension had the strongest link, with hypertensive participants exhibiting more substantial structural deterioration.

    These findings suggest maintaining good cardiovascular and metabolic health may help slow brain aging. Hypertension damages the brain’s microvasculature. Learn how exercise preserves these tiny blood vessels, helping to maintain cognitive health.

  • Conventional wisdom suggests that cognitive skills begin to decline in early adulthood, but this assumption may be misleading. A recent study found that cognitive skills—specifically math and reading skills—actually improve into one’s forties before experiencing a decline, and using these skills regularly is crucial in determining how abilities change over time.

    Researchers analyzed data from a previous German study that monitored more than 3,200 adult participants over time, allowing for the identification of genuine age-related changes in cognitive abilities. They also considered measurement errors that could skew results.

    They found that math and reading skills continued to improve into the participants' forties. After that, literacy declined slightly, while numeracy dropped more sharply—but only for participants with below-average skill usage. Those who regularly engaged in complex tasks at work or home, particularly white-collar and highly educated participants, maintained or improved their skills well beyond midlife. However, women experienced steeper declines in numeracy as they aged.

    These findings suggest that cognitive decline is not inevitable. Remaining mentally engaged through work and daily activities may help preserve or enhance cognitive abilities beyond middle age. Maintaining healthy blood flow to the brain through vigorous exercise can support cognitive function in aging. Learn more in this episode featuring Dr. Rhonda Patrick.

  • A lively social life might be one of the best defenses against dementia. With more than 50 million people affected worldwide and care costs soaring into the hundreds of billions, finding ways to delay dementia is a public health priority. A recent study found that older adults who were more socially active developed dementia about five years later than those who were the least socially engaged.

    Researchers tracked nearly 2,000 older adults without dementia as part of the Rush Memory and Aging Project. Each year, participants underwent cognitive assessments to determine whether they had developed mild cognitive impairment or dementia.

    Over nearly seven years of follow-up, 545 participants developed dementia, and 695 developed mild cognitive impairment. On average, the least socially active participants developed dementia at about age 87, while the most socially active participants developed it at about age 92—a five-year difference. The same pattern emerged for mild cognitive impairment.

    These findings suggest that social activity could be a powerful, community-wide strategy for delaying dementia, ultimately improving older adults' quality of life and reducing healthcare costs. Dietary components, including omega-3 fatty acids, play a critical role in reducing the risk of dementia, too. Learn more in this episode featuring Dr. Rhonda Patrick.

  • About half of your brain is white matter—a network of nerve fibers that allow for the exchange of information and communication within the brain. Aging and lifestyle factors can damage the white matter, increasing the risk of stroke, dementia, and disability. However, a recent study found that the brains of regular green tea drinkers have fewer white matter lesions than non-drinkers.

    The study included nearly 8,800 older adults living in Japan. Participants provided information about their green tea and coffee consumption and underwent magnetic resonance imaging to assess their brain health and volume.

    They found that higher green tea consumption correlated with fewer cerebral white matter lesions but had little effect on brain volumes, even after accounting for demographic, lifestyle, and health factors. People who drank about three cups (~20 ounces) of green tea daily had 3% less white matter damage in their brains than those who drank just one cup (~7 ounces). Those who drank around seven to eight glasses (~50 ounces) daily had 6% less damage. Coffee consumption did not affect white matter or brain volume, suggesting that green tea protects against white matter damage.

    Green tea contains epigallocatechin gallate (EGCG), a polyphenolic compound that exerts robust antioxidant, anti-inflammatory, and neuroprotective effects. Evidence suggests that EGCG reduces the buildup of amyloid beta and tau—two proteins involved in the pathophysiology of Alzheimer’s disease. Learn more about EGCG and other polyphenols in our overview article.

  • Flaxseed oil is rich in alpha-linolenic acid (ALA), an omega-3 fatty acid. In the liver, ALA converts to docosahexaenoic acid (DHA), a crucial component of brain health. Evidence suggests that low DHA levels can impair cognitive function. However, a recent study in older adults found that supplemental flaxseed oil enhances cognitive function, particularly verbal fluency—the ability to retrieve and use words quickly.

    The study involved 60 cognitively healthy older adults between the ages of 65 and 80. Half of the participants received 3.7 grams of flaxseed oil containing 2.2 grams of ALA daily for 12 weeks, and the other half received corn oil. Before and after the intervention, researchers assessed aspects of their cognitive function, including verbal fluency.

    Verbal fluency relies on several cognitive skills, including recalling word meanings, finding the right words quickly, processing information efficiently, controlling impulses, holding and using information in the moment, switching between tasks or ideas, and adapting to new situations. It also involves multiple areas of the brain working together. Unfortunately, verbal fluency declines with age, impairing conversation and social interactions and serving as a predictor of Alzheimer’s disease.

    The researchers found that participants who received the ALA-rich flaxseed oil supplement had higher verbal fluency than their peers who received the corn oil, suggesting that flaxseed oil is suitable for delivering crucial omega-3s to the brain. Learn more about the effects of omega-3s on brain health in this clip featuring Dr. Axel Montagne.

  • Eggs are a dietary paradox: high in cholesterol but rich in brain-boosting nutrients, including choline, lutein, and zeaxanthin. While some studies indicate that eggs maintain cognitive health, others report the converse. A recent study found that eating eggs may help women preserve semantic memory—crucial for language comprehension and factual recall—as they age.

    Researchers analyzed data from 890 adults aged 55 and older. Participants reported their egg consumption using a food frequency questionnaire, and researchers measured their memory and thinking skills at two clinic visits about four years apart.

    They found that women who ate five eggs weekly experienced less decline in verbal fluency, a measure of semantic memory, than those who ate fewer eggs. In men, researchers found no clear relationship between egg intake and changes in cognitive performance. Eating eggs did not appear to harm cognitive function in either sex.

    These findings suggest that eggs play a small but beneficial role in preserving memory in women. They also align with other research demonstrating that people with moderate choline intake—roughly the amount in two eggs—are about half as likely to have low cognitive function than those with the lowest intake.

  • Frailty isn’t just about getting older—it’s a key indicator of biological age that can signal an increased risk for many health concerns, including dementia. A recent study found that rapid increases in frailty increase the risk of dementia by as much as 73%, especially among females.

    Researchers analyzed data from four large studies involving nearly 88,000 adults aged 60 and older. They measured participants' frailty levels at the start and monitored their health, including the development of dementia, over several years.

    They found that in the years before dementia began to manifest, frailty tended to increase. Participants with the most rapid increases in frailty were 18% to 73% more likely to develop dementia than those with slower frailty progression. Frailty was more common in females than males among those who developed dementia, with the greatest differences seen in the years leading up to dementia onset.

    These findings suggest that measuring frailty could help identify people at greater risk for dementia, serving as an early target for strategies to reduce dementia risk through public health interventions and lifestyle changes. One powerful lifestyle approach for reducing dementia risk is exercise—especially the vigorous kind. Learn more in this episode featuring Dr. Rhonda Patrick.

  • Rapamycin, a compound initially discovered as an antifungal agent, has garnered considerable interest in longevity research due to its ability to inhibit mTOR, a protein that plays a critical role in cellular growth and aging. Studies in animal models have demonstrated rapamycin’s potential to extend lifespan and improve healthspan. However, translating these findings into human applications has proven complex, as substantial risks often accompany the benefits.

    Bryan Johnson is an internet personality who has made a name for himself by talking about his sometimes extravagant n=1 biohacking attempts to reverse aging. Recently, Johnson announced a reversal on his position on rapamycin: He thinks it might be making him age worse.

    Johnson tested various rapamycin dosing protocols to explore its anti-aging potential while minimizing adverse effects. These protocols included weekly doses of 5, 6, and 10 milligrams, biweekly doses of 13 milligrams, and an alternating weekly schedule of 6 and 13 milligrams.

    Although data from preclinical trials were promising, Johnson concluded that the long-term use of rapamycin in humans does not outweigh its drawbacks. Side effects, including intermittent skin and soft tissue infections, impaired lipid metabolism, elevated glucose levels, and increased resting heart rate, persisted regardless of dosage adjustments. After ruling out other potential causes, he attributed these issues to rapamycin and ultimately decided to discontinue its use.

    Other research supports his observations, demonstrating that chronic rapamycin use can impair lipid profiles, induce insulin resistance, and contribute to glucose intolerance and pancreatic beta-cell toxicity. While anecdotal evidence suggests that rapamycin may slow tumor growth, its suppression of natural killer cells raises concerns about impaired immune surveillance and potentially increased cancer risk over time.

    Further complicating the picture, a recent pre-print study presented new findings about rapamycin’s effects on aging. The study assessed the effects of rapamycin across 16 epigenetic aging clocks and found that it accelerated aging markers in humans. This analysis is noteworthy because most assessments have relied on only one or two aging clocks, raising concerns about the reliability of the findings.

    As Johnson notes, longevity research is a rapidly evolving field that requires continuous scrutiny of emerging studies and biomarkers. For now, his experience underscores the importance of balancing potential benefits against risks when exploring experimental compounds like rapamycin. Learn more about rapamycin in our overview article.

  • Brain atrophy occurs naturally with aging, but certain factors such as type 2 diabetes, high blood pressure, and inflammation can accelerate this process, increasing the risk of cognitive decline. However, eating a healthy diet may help slow brain aging. A recent study found that two versions of the Mediterranean diet reduced markers of brain atrophy by 50% over 18 months compared to general healthy eating guidelines.

    Researchers assigned participants aged 50 or older with abdominal obesity or abnormal blood lipids to one of three diets: one that followed standard healthy dietary guidelines, a calorie-restricted Mediterranean diet (which included walnuts and olive oil and substituted chicken and fish for lamb and beef), or a “green” calorie-restricted Mediterranean diet enriched with polyphenols from green tea and mankai, an aquatic plant. The participants underwent brain imaging to assess hippocampal atrophy, a key marker of brain aging, and the researchers tracked changes in body weight, blood sugar, and inflammation over the study period.

    Participants following the green Mediterranean diet showed the greatest preservation of brain volume, particularly in the hippocampus. They also experienced improvements in HbA1c (a marker of long-term blood glucose control), insulin resistance, fasting glucose, and C-reactive protein. Improvements in blood sugar levels and inflammation were closely linked to better brain health outcomes, and greater intake of polyphenol-rich foods like mankai and green tea further enhanced these benefits.

    Mankai, also called duckweed, is rich in polyphenols, omega-3 fatty acids, dietary fiber, and many micronutrients, including iron and vitamin B12. The polyphenols in mankai exert robust antioxidant activity and support healthy blood glucose levels—critical elements in maintaining brain health.

    These findings suggest that diets rich in polyphenols and designed to improve metabolic health may help protect against age-related brain atrophy and keep the brain biologically younger. Learn more about the health benefits of polyphenols in our overview article.

  • Keeping our hearts strong and healthy becomes increasingly challenging as we age, especially for older women. However, physical activity, especially resistance training, may benefit the heart. A recent study found that a 24-week resistance training program improved heart function in older women.

    Researchers assigned 73 physically independent older women (average age, 68) to either an exercise training or sedentary group. The training group participated in a supervised resistance training program three times weekly for 24 weeks, using machines and free weights. Each session included exercises targeting the whole body, with three sets of eight to 12 repetitions each. The researchers measured the participants' cardiac function before and after the program.

    They found that women in the training group experienced several improvements in heart function, including: - A 10.6% decrease in left ventricular volume versus a 1.1% increase in the sedentary group. - A 9.1% decrease in left atrial volume versus a 3.9% increase in the sedentary group. - Better heart relaxation, indicated by a 4.8% reduction in the diastolic function index.

    These findings suggest that regular resistance training improves heart structure and function in older women, potentially reducing the risk of age-related cardiac decline. Finding the time for resistance training can be difficult, however. Listen as Drs. Brad Schoenfeld and Stuart Phillips describe time-efficient ways to incorporate resistance training into a busy schedule.

  • Research demonstrates that inflammation in later life harms the brain, increasing the risk of dementia and cognitive decline. However, scientists don’t fully understand the effects of inflammation that begins in early adulthood. A recent study found that inflammation during early adulthood markedly impairs cognitive performance in midlife.

    The research involved more than 2,300 young adults (aged 24 to 58) enrolled in the Coronary Artery Risk Development in Young Adults study. Researchers tracked the participants' inflammation levels, measured by C-reactive protein (CRP), for about 18 years. Five years after their last CRP measurement, the participants completed tests that measured their verbal memory, processing speed, executive function, verbal fluency, category fluency, and overall cognition.

    The researchers identified three inflammation patterns among the participants: lower stable (45%), moderate/increasing (16%), and consistently higher (39%). Participants with consistently higher CRP levels were 67 percent more likely to experience poor processing speed and 36 percent more likely to have poor executive function than those with stable, low CRP levels. Those with moderate/increasing CRP levels were twice as likely to have poor processing speed. There were no significant associations between CRP levels and memory, verbal fluency, category fluency, or overall cognition.

    One of the many ways inflammation harms the brain is through its effects on pericytes, tiny cells that surround the brain’s blood vessels and help maintain the blood-brain barrier. Inflammation causes pericytes to release pro-inflammatory cytokines, compromising the barrier and facilitating neurodegeneration. Learn more about links between inflammation, pericytes, and cognitive decline in this clip featuring Dr. Axel Montagne.

    These findings indicate that more than one-third of young adults have high inflammation levels, adversely affecting executive function and processing speed by midlife. They also underscore the importance of managing inflammation throughout life. Omega-3 fatty acids have potent anti-inflammatory effects. Learn more in this episode featuring Dr. Bill Harris.

  • The skin is the body’s first line of defense against environmental exposures. However, the skin changes considerably as we age, reducing its defense capacity. A 2021 study in mice found that sulforaphane, a bioactive compound derived from broccoli, mitigates age-related skin changes by activating Nrf2, a protein that participates in the body’s antioxidant defense system.

    Researchers fed young and old mice regular mouse chow or chow supplemented with sulforaphane for three months. They assessed the antioxidant capacity and protein expression levels in the animals' skin. They also measured levels of reactive oxygen species and matrix metalloproteinase-9 (MMP9, a protein involved in tissue remodeling, inflammation, and wound healing), assessed epidermal and dermal thickness changes, and analyzed collagen content.

    They found that sulforaphane reduced reactive oxygen species and MMP9 levels in older mice. It also increased the skin’s antioxidant capacity, as evidenced by enhanced Nrf2 production. They observed no difference in epidermal thickness between young and old SFN-treated mice, but dermal layers were thinner in older mice. Collagen content improved in young and old mice, with more substantial structural improvements observed in the older group.

    These findings suggest that dietary supplementation with sulforaphane ameliorates age-related skin changes in mice by activating the Nrf2 pathway, enhancing antioxidant defenses and reducing oxidative stress.

    Notably, the dose provided in this mouse study was very high, translating to about 2,500 milligrams of sulforaphane in humans – roughly the amount supplied in 63 cups of broccoli sprouts. Nevertheless, sulforaphane’s antioxidant-inducing capacity is well established, and consumption of sulforaphane-rich foods is associated with increased healthspan and lifespan. Broccoli sprouts are excellent sources of sulforaphane and are easy to grow at home. For tips on how to grow broccoli sprouts, check out our comprehensive Sprouting Guide, a members-only perk.

  • While brain aging is an inevitable part of growing older, lifestyle factors, particularly diet, can influence the rate at which this aging occurs. A recent study found that older adults with diets rich in omega-3 fatty acids, antioxidants, and vitamins demonstrate slower brain aging and better performance on cognitive tests.

    Researchers administered cognitive tests and brain imaging scans to 100 healthy older adults. They also measured 13 nutrition-related biomarkers in the participants' blood.

    They identified two brain aging patterns among the participants, with one group exhibiting accelerated aging and the other slower aging. Further analysis revealed that distinct dietary patterns distinguished the two groups. In particular, the intake of specific nutrients positively influenced brain health and cognitive function, including: - Alpha-linolenic acid (an omega-3 fatty acid found in nuts and seeds, such as walnuts and chia) - Eicosapentaenoic acid (an omega-3 fatty acid found in fatty fish, such as salmon) - Lutein (a polyphenol found in green leafy vegetables, such as kale) - Zeaxanthin (a polyphenol found in brightly colored vegetables, such as orange bell peppers and butternut squash) - Vitamin E (found in seeds and nuts, such as sunflower seeds and hazelnuts) - Choline (found in a variety of foods, including eggs and soybeans) These patterns were consistent even when considering the participants' demographics, fitness levels, and body measurements.

    These findings suggest that nutrient-rich diets are critical for maintaining cognitive health and decelerating the brain’s aging process. They also highlight the importance of dietary choices as potential tools to manage and mitigate age-related cognitive decline. Learn about other lifestyle choices that slow cognitive and physical aging in this episode featuring Dr. Rhonda Patrick.

  • As the global population ages, the number of people at risk for Alzheimer’s disease and other forms of dementia increases. A robust and growing body of evidence indicates that lifestyle influences the risk of developing dementia. A recent study found that multivitamin/mineral supplements improve memory and slow cognitive aging in older adults – roughly equivalent to reducing cognitive aging by two years.

    Researchers investigated the effects of multivitamin/mineral supplementation on cognitive function in a subset of participants enrolled in the COSMOS study, a randomized, double-blind, placebo-controlled trial involving more than 21,000 older adults (60 years or older) in the U.S. Participants in COSMOS were randomly assigned to receive one of three interventions: cocoa extract (providing 500 milligrams of flavanols daily, including 80 milligrams of epicatechin), a multivitamin/mineral supplement, or both, daily for two years. A fourth group received a placebo. In the subset, called COSMOS-Clinic, 573 participants underwent extensive brain function tests before and after the study and again two years later.

    They found that multivitamin/mineral supplementation conferred modest improvements in overall cognitive function over two years in participants enrolled in the subset, particularly in episodic memory – the ability to recall specific events, experiences, and contextual details from one’s past. They did not observe improvements in the participants' executive function or attention. However, a meta-analysis involving more than 5,000 participants from the COSMOS-Clinic, COSMOS-Mind, and COSMOS-Web studies demonstrated that multivitamin/mineral supplementation markedly improved overall cognition and episodic memory.

    These findings from the COSMOS trials suggest that multivitamin/mineral supplementation – a low-cost, low-effort intervention – improves cognitive function in older adults. They also highlight the role of adequate nutrition throughout the lifespan and support the “micronutrient triage theory” – the idea that the body prioritizes the utilization of micronutrients for metabolic pathways needed for survival and reproduction over those used for long-term health. Learn more about micronutrient triage theory in this clip featuring Dr. Bruce Ames.

  • Muscle mass declines markedly with age, with up to 8 percent muscle mass loss occurring per decade after age 30. Evidence suggests that naringenin, a flavonoid compound found in citrus fruits, maintains muscle mass in aging. Mice that ate a diet supplemented with naringenin showed improved muscle endurance and grip strength.

    Researchers supplemented the diets of young adult mice, middle-aged mice, and mice prone to muscular dystrophy (accelerated muscle loss) with naringenin. Then, they assessed naringenin’s effects on exercise capacity and aerobic metabolic levels in skeletal muscle.

    They found that young adult and middle-aged mice receiving naringenin could run farther than those that did not. Middle-aged mice also showed improved grip strength and increased calf muscle size. Mice prone to developing muscular dystrophy ran farther and showed improved grip strength.

    The researchers attributed these improvements in muscle endurance to naringenin’s capacity to increase the number of oxidative myofibers (muscle fibers that use oxygen) and improve the overall efficiency of aerobic metabolism in the body. They found that Sp1, a transcription factor that influences gene expression in muscle, likely mediated naringenin’s effects.

    These findings indicate that naringenin may preserve muscle mass in aging and disease. Other dietary components, such as omega-3 fatty acids, influence muscle maintenance, too. Learn more in this episode featuring Dr. Chris McGlory.

  • Vitamin D, best known for maintaining calcium balance and bone health, is critical in many physiological processes, including blood pressure regulation, immune function, and cell growth. Evidence now suggests vitamin D also influences body composition and muscle strength. A recent study in mice showed that high vitamin D intake increased muscle strength and mass without altering body weight.

    Researchers fed mice one of three diets, providing low, normal, and high doses of vitamin D for four weeks to achieve deficient, insufficient, and sufficient vitamin D concentrations, respectively. At the end of the fourth week, they assessed the animals' grip strength (a measure of muscle function) and body composition.

    They found that compared to low or normal vitamin D intake, high intake increased grip strength and lean mass and decreased fat mass without altering the animals' weights. High intake also impaired myostatin production and increased the animals' leptin sensitivity and energy expenditure without altering their activity levels.

    Leptin is a satiety hormone that signals the brain to balance energy. When body fat increases or decreases, blood concentrations of leptin change accordingly. Higher leptin levels signal the brain to reduce hunger and boost energy use. However, in obesity, the body becomes less responsive to leptin, dulling its effects on appetite and energy expenditure.

    These findings suggest that vitamin D influences body composition and metabolism by preferentially allocating calories toward muscle development and overall growth rather than fat storage. They also highlight the intricate relationship between obesity and vitamin D status. Learn more about vitamin D in our comprehensive overview article.

  • Nearly 50 million people worldwide live with Alzheimer’s disease or another form of dementia — a number projected to triple in the coming decades. However, a recent study suggests the number could be even higher, as much as 40 percent more than previous estimates.

    Researchers analyzed data from the English Longitudinal Study of Ageing, a long-term study of older adults living in England and Wales. They identified dementia cases from among more than 90,000 people. Then, they analyzed how dementia incidence changed over time based on age, sex, and education.

    They found that dementia incidence decreased by 28.8 percent between 2002 and 2008 and then increased by 25.2 percent between 2008 and 2016 (nearly 3 percent per year). People with lower educational attainment experienced a slower decline in dementia during 2002-2008 and a more rapid increase after 2008, demonstrating growing disparities. The researchers predicted that if dementia incidence continues to rise at the same pace observed from 2008 to 2016, the number of people living with dementia will roughly double by 2040.

    These findings suggest that the number of people with dementia will be markedly higher in the coming decades. Evidence suggests lifestyle factors influence a person’s dementia risk. Learn how sauna use, exercise, sleep, and dietary components, such as omega-3 fatty acids and sulforaphane exert robust anti-aging effects on the brain, potentially preventing or forestalling dementia.

  • Delta-9-tetrahydrocannabinol – better known as THC – is the primary psychoactive compound found in cannabis. THC binds to endocannabinoid system receptors, eliciting a wide range of physical effects and producing the “high” associated with its use. A new study suggests that THC reverses brain aging in old mice.

    Researchers injected old mice with a microdose of THC that was roughly three to four orders of magnitude lower than a typical dose. Then, they assessed gene expression in the animals' hippocampal tissue at five days and five weeks post-treatment.

    After just five days, they found that the microdose THC treatment altered the expression of 18 genes related to neurogenesis (the production of new nerve cells). THC altered the expression of 88 genes related to nerve cell survival and development five weeks post-treatment. Interestingly, THC did not affect brain-derived neurotrophic factor, a protein noted for its effects on neurogenesis.

    These findings suggest that a single microdose of THC exerts potent, enduring effects on the rodent brain and may have potential applications in humans. It also aligns with results from a compelling case study in which THC microdosing ameliorated symptoms of Alzheimer’s disease. Lactate, a molecule produced during vigorous exercise, also has robust effects on the brain, influencing neurogenesis and promoting cognitive function. Learn more in this episode featuring Dr. George Brooks.

  • Hip fractures can lead to a decline in self-reliance, diminished quality of life, and feelings of depression. However, some research suggests that consuming fish and omega-3 fatty acids influences a person’s risk of experiencing a hip fracture. A 2019 meta-analysis and systematic review found that higher fish and omega-3 intake reduces the risk of hip fracture by as much as 12 percent.

    Researchers reviewed the findings of 10 studies involving nearly 300,000 people. Seven of the studies followed people over time (prospective), and three compared groups with and without fractures (case-control).

    They found that people who consumed more fish had a lower risk of hip fractures, even when combining the results from prospective and case-control studies. They found the same protective effect for those who consumed higher omega-3s in their diets. Notably, the protective effect of fish and omega-3 intake remained only when considering larger prospective studies (involving 10,000 participants or more) or studies that included body mass index as a factor.

    These findings suggest that dietary intake of fish and omega-3s might promote bone health and reduce the risk of hip fractures. Other studies have proposed mechanisms by which omega-3s exert their beneficial effects. For example, one study found that DHA inhibits osteoclast formation and subsequent bone resorption by inhibiting the production of TNF-alpha, a pro-inflammatory molecule. A separate study demonstrated that resolvin, a byproduct of omega-3 metabolism, promotes bone preservation under inflammatory conditions and influences the PI3K-AKT pathway, a major signaling pathway implicated in many human diseases, including osteoporosis.

  • Ultraviolet (UV) light exposure – from the sun or tanning beds – causes premature skin aging, a process called photoaging. But a new study in mice found that supplemental collagen, which is rich in the glycine-proline dipeptide, protects against the damaging effects of UV light exposure. Mice that received collagen during regular exposure to UV light had fewer wrinkles and other signs of photoaging than those that didn’t.

    Researchers exposed young mice to one of four treatments for 12 weeks: UV light only; UV light plus low-dose collagen (300 milligrams per kilogram); UV light plus high-dose collagen (500 milligrams per kilogram); or neither exposure. They measured the animals' plasma collagen concentrations, and then, at the end of the study, they assessed the animals' skin for signs of photoaging.

    They found that collagen concentrations increased considerably within 30 minutes of consumption. They also found that both low- and high-dose collagen reduced wrinkle development and skin thinning and improved the skin’s hydration.

    These findings suggest supplemental collagen protects against photoaging in mice, aligning with a recent review and meta-analysis. Interestingly, some evidence suggests collagen supplementation in the setting of exercise recovery reduces joint pain and improves joint functionality but appears to have no significant effect on post-exercise muscle protein synthesis necessary for hypertrophy and muscle collagen protein synthesis.

  • Lipid rafts – cholesterol-filled “bubbles” found in neuronal cell membranes – play a crucial role in synaptic plasticity and memory formation. However, lipid rafts undergo extensive changes during aging, ultimately contributing to cognitive decline. A new study in mice shows that omega-3 fatty acids preserve lipid raft integrity and bolster cognitive function.

    Researchers fed young and old female mice a regular diet or a diet supplemented with omega-3 fatty acids. Then they examined the animals' brains to determine the omega-3s' effects on the structure and properties of the lipid rafts.

    They found that older mice fed a regular diet exhibited changes consistent with lipid raft aging, including reduced omega-3 fatty acid concentrations, increased membrane lipid saturation, and altered lipid composition. However, omega-3 supplementation reversed these changes to the point where they resembled the lipid rafts typically seen in younger mice. In addition, omega-3 supplementation influenced the distribution and accumulation of glutamate receptors and ion channels involved in synaptic plasticity, potentially influencing memory formation.

    These findings suggest that omega-3 fatty acids counteract age-related changes in the brain, specifically in lipid rafts, and preserve cognitive function and memory in aging. Learn more about omega-3s' roles in preserving cognitive function in this clip featuring Dr. Axel Montagne.

  • A diminished or lost sense of smell is a common feature of the early stages of Alzheimer’s disease and other forms of dementia. But a new study in mice that carry the APOE4 gene variant, the primary genetic risk factor for Alzheimer’s disease, shows that DHA – a type of omega-3 fatty acid found in fish – protects against these losses. APOE4-carrying mice that ate a DHA-rich diet retained their sense of smell and the ability to distinguish between objects based on their scent.

    Researchers fed normal mice and APOE4 carriers a regular diet or one supplemented with DHA. Then, using MRI scans, they assessed the animals' brain structures and studied their behavior related to smell and the recognition of new objects. They also measured biomarkers related to cell death and inflammation.

    They found that the APOE4-carrying mice given a regular diet exhibited memory deficits and difficulty adjusting to new smells and distinguishing between different objects. In addition, their brains showed increased signs of inflammation in the olfactory bulb – the area responsible for the sense of smell. However, APOE4-carrying mice that ate the DHA-rich diet did not exhibit these characteristics.

    These findings suggest that a DHA-rich diet benefits APOE4 carriers. Learn more about the beneficial effects of DHA in our comprehensive omega-3 overview article.

  • Aerobic exercise has profound effects on the human body – including the skin. Now findings from a new study suggest that resistance training slows skin aging. Women who engaged in resistance training had thicker, more resilient skin than women who engaged in aerobic exercise alone.

    Researchers compared the effects of aerobic versus resistance training on skin aging in 56 sedentary, middle-aged women. The participants engaged in a twice-weekly supervised exercise program involving either aerobic or resistance training for 16 weeks. The researchers evaluated the participants' skin properties, body composition, and physical capacity before and after the intervention.

    They found that both types of training improved skin elasticity and structure, but only resistance training increased the thickness of the dermis, the inner layer of the skin. Resistance training also increased levels of biglycan, a protein that promotes wound healing and skin resilience via its interactions with collagen. The researchers also noted an increase in the expression of genes related to the skin cells' extracellular matrix.

    These findings suggest that resistance training enhances several aspects of skin health, slowing the effects of skin aging. They also highlight yet another way in which resistance training bolsters health. Learn about other strategies to promote healthy, resilient skin in this Aliquot featuring Dr. Rhonda Patrick.

  • Changes in brain function and connectivity often occur many years before the clinical manifestation of cognitive impairment and dementia. A new study shows that lifestyle modifications, including exercise, vitamin D intake, and cognitive training, improve functional brain connectivity in older adults with mild cognitive impairment.

    The study involved 120 older adults (ages 60 to 80 years) with mild cognitive impairment. The participants engaged in 30 minutes of cognitive training and 60 minutes of exercise three times a week for 20 weeks. Thirty-eight of the participants received vitamin D supplements, while the remainder received a placebo. Researchers measured the participants' functional brain connectivity using MRI before and after the interventions.

    They found that physical exercise alone, exercise combined with cognitive training, or exercise combined with both cognitive training and vitamin D supplementation increased functional brain connectivity in regions of the brain’s default mode network, including the hippocampus and angular gyrus.

    The default mode network is a collection of interconnected neural structures involved in attention and focus. Disturbances in default mode network connectivity are associated with poor working memory, reduced performance, and work-related productivity losses.

    This study’s findings suggest that lifestyle behaviors, particularly exercise, enhance functional brain connectivity, potentially staving off age-associated cognitive decline. Learn more about the effects of exercise on the brain in this episode featuring Dr. Axel Montagne.

  • The immune system plays important, and sometimes surprising, roles in brain health. A new study in mice found that blocking components of the antiviral immune response may make the brain more resilient to the effects of abnormal tau – potentially preventing Alzheimer’s disease and other forms of dementia.

    Tau is a protein found in the brain. Abnormal tau can form aggregates called tau tangles – one of the defining characteristics of Alzheimer’s disease – activating antiviral response pathways and interfering with normal brain function and cognition.

    Researchers studied the effects of exposure to abnormal tau on microglia, the brain’s resident immune cells. They found that when microglia were exposed to abnormal tau, the mitochondria became “leaky,” releasing their DNA into the cellular fluid. The immune system inappropriately interpreted the leaked DNA as a viral attack, triggering an immune response that promoted the release of type-I interferon, a cytokine that drives the antiviral immune response. Interrupting the pathways involved in this response restored normal brain function.

    These findings suggest that suppressing the inappropriate immune response to abnormal tau exposure could provide a means to prevent or treat the tau-associated pathologies common in Alzheimer’s disease and dementia. Learn about other strategies to reduce the risk of Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

  • Experiencing multiple concussions increases a person’s risk of poor brain function later in life, a new study shows. People who experienced three or more concussions exhibited cognitive deficits that worsened with each subsequent concussion.

    Researchers collected self-reported concussion histories from more than 5,700 adults between 50 and 70 years old. They administered cognitive tests to gauge changes in the participants' brain function every year for up to four years.

    They found that participants who experienced three mild concussions in their lifetime had difficulty with attention and performing complex tasks later in life. Participants who experienced four mild concussions had difficulty with processing speed and working memory – an aspect of cognitive function that allows a person to remember information for relevant tasks. However, experiencing even one moderate-to-severe concussion impaired the participants' attention and the ability to perform complex tasks and process information.

    These findings underscore the risks associated with even mild brain injury. Some evidence suggests that lactate and ketones may be beneficial in treating brain injury. Learn more in this clip featuring Dr. Dominic D'Agostino.

  • Excess body weight drives gray matter losses similar to those seen in Alzheimer’s disease, a new study shows. The brains of people who were obese showed marked signs of gray matter atrophy in areas of the brain responsible for attention, problem-solving, and reasoning.

    Using neuroimaging data, researchers compared the grey matter patterns of more than 1,300 older adults. Participants included those with Alzheimer’s disease and those who were cognitively healthy, obese but otherwise healthy, or lean.

    The scientists found that obesity and Alzheimer’s disease had similar effects on the brain. Both conditions were associated with gray matter atrophy in the right temporoparietal cortex (an area involved in attention) and the left prefrontal cortex (an area involved in reason, problem-solving, and comprehension). They also found that obesity-related gray matter atrophy patterns didn’t overlap with amyloid-beta or tau protein distribution in the brains of people with Alzheimer’s disease. Amyloid-beta and tau accumulation are widely considered hallmarks of Alzheimer’s disease.

    Excess body weight drives many metabolic disorders, including type 2 diabetes, hypertension, and dyslipidemia. Recent evidence demonstrates that excess body weight impairs cognitive function. The findings from this study suggest that excess body weight drives gray matter losses similar to those seen in Alzheimer’s disease.

  • Growth hormone improves bone density and reduces the risk of fractures in women with osteoporosis, according to a 2015 study. Women who received growth hormone were half as likely to experience a fracture over a 10-year period than women who did not.

    The study involved 80 women (50 to 70 years old) who had osteoporosis and were taking estrogen-based hormone replacement therapy. Researchers randomly assigned the women to receive daily injections of either a low or high dose of growth hormone for three years or a placebo for 18 months. All the women took daily vitamin D and calcium supplements for the study’s duration. The researchers measured the women’s body composition and bone mass at regular intervals.

    They found that women who received growth hormone injections showed marked improvements in their bone mineral density and bone mineral content compared to those who received the placebo. Over the 10-year period, the number of fractures among the women who received growth hormone dropped from 56 percent to 28 percent, whereas fractures among those who received the placebo increased from 8 percent to 32 percent.

    Growth hormone, a peptide hormone produced in the pineal gland, promotes growth in childhood and adolescence. During middle age, growth hormone production decreases. Some evidence suggests that because growth hormone is secreted at night (during sleep), not getting enough sleep may hinder growth hormone release, exacerbating age-related bone loss. Learn how body temperature can influence how well you sleep at night in this clip featuring Dr. Matthew Walker.

  • Gradual increases in blood pressure from young adulthood to middle age increased the risk of poor brain health in older age, a 2022 study found. Having higher blood pressure over time damaged the brain’s delicate blood vessels, reducing blood flow to the brain.

    The study involved 885 adults whose blood pressures were monitored regularly over a 30-year period. Using magnetic resonance imaging studies, researchers assessed the participants' brain health at the beginning and end of the study period.

    The researchers found that participants who had either high blood pressure in young adulthood or moderate blood pressure that gradually increased over time showed marked signs of microvascular disease in the white matter of their brains. The two groups also showed reduced blood flow in the gray matter of their brains.

    Microvascular disease, also called small vessel disease, is a condition characterized by blood vessel dysfunction. It commonly occurs with aging and contributes to the development of cardiovascular disease, dementia, and stroke. Small vessel disease in the brain contributes to approximately 50 percent of dementia cases worldwide.

  • Older adults who regularly bathed in hot springs in the evening were less likely to have hypertension, a new study has found. Having hypertension markedly increased the likelihood of having other chronic diseases, however.

    Researchers gathered information about the hot spring bathing habits and overall health of more than 10,000 older adults. The participants lived near Beppu, Japan, an area known for its many hot springs.

    They found that older adults who regularly bathed in hot springs in the evening were approximately 15 percent less likely to have hypertension. Older adults who didn’t frequent the hot springs were roughly 50 percent more likely to have type 2 diabetes, heart arrhythmia, stroke, gout, or abnormal blood lipids.

    Evidence suggests that chronic mental stress promotes hypertension. Research has shown that bathing in hot springs improves mental health and reduces stress. Other research has shown that hot water bathing before bedtime promotes faster sleep onset and better sleep quality, which could reduce the risk of developing hypertension.

    Exercise, hot baths, and sauna use may have similar effects on promoting sleep and reducing blood pressure. Learn more about the effects of sauna use on hypertension in this clip featuring Dr. Jari Laukkanen.

  • Older adults who engage in leisure time physical activities have lower risk of premature death.

    Leisure time physical activity is a broad term that refers to physical activities performed outside work or typical household responsibilities. Examples include exercise, sports, dancing, gardening, and walking. Findings from a recent study suggest that certain leisure time physical activities are associated with a lower risk of death from all causes of premature death, including cardiovascular disease and cancer, in older adults.

    Most public health organizations recommend that adults of all ages should engage in at least 150 minutes of moderate-intensity aerobic physical exercise or at least 75 minutes of vigorous-intensity aerobic physical exercise each week, or an equivalent combination of both. The bulk of the research focused on the benefits of physical activity has been in younger people, the findings of which might not be translatable to older adults.

    The investigators drew on data from 272,500 older adults (average age, 70 years) enrolled in the National Institutes of Health-AARP Diet and Health Study, an ongoing study of associations between diet and cancer. Participants provided information about their demographics, height, weight, smoking status, mood, educational level, and alcohol consumption. They also answered questions about the average amount of time they spent per week during the previous year engaging in cycling, swimming laps, playing racquet sports, playing golf, walking for exercise, jogging or running, and other aerobic exercises. The investigators calculated the participants' average leisure time activity levels in terms of metabolic equivalents, or METs, a measure of the rate of energy expended per unit of time.

    They found that playing racquet sports was associated with a 16 percent reduction in the risk of death from any cause and running was associated with a 15 percent reduction. The other activities conferred protection as well, but to a lesser extent. Achieving the recommended amount of physical activity through any combination of the seven leisure time activities reduced the risk of death by 13 percent. The protective effects of leisure time physical activity were dose-dependent to a degree, with greater duration conferring greater reduction in risk, but levels beyond those recommended showed diminishing returns.

    These findings suggest that older adults who meet physical activity guidelines through leisure time physical activities, especially aerobic activities such as racquet sports or running, have a reduced risk of premature death from all causes. Learn about the benefits of aerobic exercise in our overview article.

  • The DASH Diet slows epigenetic aging.

    The DASH Diet (Dietary Approaches to Stop Hypertension) is a dietary pattern that emphasizes heart-healthy eating. Widely recognized for its evidence-based guidelines, DASH is rich in fruits, vegetables, fish, poultry, legumes, and healthy fats and is low in saturated fats and sweets. Findings from a 2021 study suggest that the DASH diet slows epigenetic aging.

    Epigenetic age acceleration is a phenomenon that occurs when an individual’s epigenetic (biological) age exceeds their chronological age. Early research relied on measures of either intrinsic or extrinsic factors to measure age acceleration. Newer methods rely on clinical and functional biomarkers, which have stronger predictive abilities for the time to chronic diseases and death.

    The study utilized data from nearly 2,000 adults (average age, 67 years) who were enrolled in the Framingham Heart Study Offspring Cohort. Investigators collected information about the participants' usual dietary intake and assigned a score based on the overall quality and adherence to DASH guidelines. They also collected blood samples from the participants for analysis and determination of their DNA methylation status using three epigenetic age acceleration measures: Dunedin Pace of Aging Methylation, GrimAge acceleration, and PhenoAge acceleration.

    They found that all three age acceleration measures indicated that having a higher DASH score was associated with slowed epigenetic aging, even after taking age, sex, smoking status, body mass index, physical activity, alcohol consumption, and caloric intake into consideration. This slow aging translated to roughly one additional year of life. Higher intakes of vegetables, fruits, nuts, legumes, and whole grains were associated with slower aging, while higher intakes of red and processed meat and sodium were associated with faster aging.

    These findings suggest that the DASH dietary pattern slow epigenetic aging and underscores the importance of implementing lifestyle modifications to promote health and longevity. Learn more about epigenetic age acceleration in these clips featuring epigenetics experts Dr. Steve Horvath and Dr. Morgan Levine.

  • From the article:

    The study found the lifetime risk of an abdominal aortic aneurysm were: 1 in 17 among all study participants; 1 in 9 among current smokers; 1 in 9 among those in the top third of smoking pack-years (number of cigarettes smoked over a lifetime), whether a current or former smoker; 1 in 12 among current female smokers.

    Researchers also found those who had quit smoking for 3-8 years (recent quitters) still had an approximately 2.6 to 3.5 fold increased risk for both clinical and asymptomatic abdominal aortic aneurysm in the next 15 years compared to never smokers. Their lifetime risk was 6.6 percent higher than long-term quitters.

    For women, authors note the steep increase in risk is particularly concerning given the United States Preventive Services Task Force recommends that current or former male smokers undergo an ultrasound screening for an abdominal aortic aneurysm once between the ages of 65 and 75 but makes no such recommendation for women.

    […]

    The study also found that being older, white, or having high levels of bad cholesterol also increased the risk of abdominal aortic aneurysm.

    View full publication

  • Gum disease may increase the risk of white matter hyperintensities, a type of brain lesion.

    White matter hyperintensities are brain lesions that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. High blood pressure is the primary contributor to white matter hyperintensity formation, but other factors likely play roles, as well. Findings from a 2020 study suggest that periodontitis is associated with white matter hyperintensities.

    Periodontitis is a chronic inflammatory condition of the gums, characterized by red, tender, swollen, or bleeding gums. It is typically caused by poor oral hygiene and is more common with age, manifesting in more than two-thirds of adults over the age of 65 years. Periodontitis is diagnosed using a periodontal probe, which is used to assess the depth of pockets in the gum. In a healthy mouth, a pocket can be anywhere from 1 to 3 millimeters deep. Deeper pockets are indicators of gum inflammation and disease.

    The study involved more than 400 adults (average age, 54 years) who underwent a routine dental exam that included pocket depth probing. The investigators performed MRI scans on the participants to identify the presence of white matter hyperintensities, which were classified according to their size, number, and severity. They gathered information about the participants' general health and lifestyles and measured their C-reactive protein (CRP, a biomarker of inflammation). They found that nearly half of the participants had white matter hyperintensities. Those who did were nearly three times more likely to be at least 65 years old, more than twice as likely to have elevated systolic blood pressure, and nearly twice as likely to have deeper pocket depth (6 millimeters or more). Having white matter hyperintensities was not associated with the participants' CRP levels.

    These findings suggest that older age, elevated blood pressure, and periodontitis are associated with an increased risk of developing white matter hyperintensities, but inflammation is not a driver of this association. Evidence indicates that white matter hyperintensities are predictive of the amount and degree of leakage of the blood-brain barrier leakage. Learn more in our overview article.

  • Strong link between accumulated visceral fat and chronic inflammation.

    A person’s waist-to-hip ratio compares their waist measurement to that of their hips. A high ratio can be an indicator of excess fat accumulation around the waist, often referred to as visceral fat. Findings from a 2005 study suggest that visceral fat is associated with markers of inflammation.

    Visceral fat is stored in the abdominal cavity near the liver, pancreas, and intestines. The accumulation of visceral fat is linked to increased risk of cardiovascular disease and other chronic diseases. Many factors drive visceral fat accumulation, including poor sleep, an obesogenic diet, and sugar-sweetened beverage intake, among others.

    The study involved more than 3,000 healthy males and females (18 to 89 years old) living in Greece. The investigators calculated the participants' body mass index (BMI) and measured their waist and hip circumferences. Participants provided blood samples for the assessment of inflammatory biomarkers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), amyloid A (an apolipoprotein secreted in the acute stage of inflammation), white blood cells, and interleukin-6 (IL-6).

    The investigators found that approximately 36 percent of the males and 43 percent of the females had excess visceral fat. Approximately 20 percent of the males and 15 percent of the females had obesity. Participants with greater visceral fat had 53 percent higher CRP, 30 percent higher TNF-alpha), 26 percent amyloid A, 17 percent higher white blood cell counts, and 42 percent higher IL-6, compared to participants with normal fat distribution. The relationship between visceral fat and inflammatory markers was stronger than that between obesity and inflammation, even when considering the participants' age, income, education, and other potential confounding factors.

    These findings suggest that visceral fat and inflammatory processes are linked. The investigators posited that excess accumulation of visceral fat may increase the risk for cardiovascular disease by driving inflammation.

  • Poor blood-brain barrier integrity drives white matter losses.

    White matter hyperintensities are areas in the brain that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. A 2021 study found that breaches in blood-brain barrier integrity are associated with brain tissue losses and precede the appearance of white matter hyperintensities.

    The blood-brain barrier, a specialized system of endothelial cells that shields the brain from toxins present in the blood, supplies the brain’s tissues with vital nutrients and substances necessary for neuronal and metabolic function. The structural integrity of the blood-brain barrier is therefore critical for homeostatic maintenance of the brain microenvironment.

    The study involved 43 patients (average age 58 years) who had been diagnosed with cerebral small vessel disease, as evidenced by having experienced a stroke or demonstrating mild cognitive impairment. At the beginning of the study and two years later, participants underwent a variety of MRI techniques that quantified their overall blood-brain barrier permeability as well as the areas surrounding white matter hyperintensities.

    The MRIs revealed that participants who had the greatest amount of leaky brain tissue at the beginning of the study exhibited greater white matter tissue losses two years later. These tissue losses translated to greater permeability, a phenomenon particularly evident in the areas surrounding the brain lesions associated with white matter hyperintensities.

    These findings suggest that losses in blood-brain barrier integrity damage brain tissue, driving increased permeability and white matter losses. In turn, these changes potentiate the disease processes associated with cerebral small vessel disease. Learn more about the blood-brain barrier in our overview article.

  • Impaired transport of DHA disrupts the blood-brain barrier.

    Lipid rafts – cholesterol-filled “bubbles” found in the cell membrane – serve as staging areas for many cellular activities. One type of lipid raft, called caveolae, facilitates the transport of substances across the membrane of endothelial cells. Findings from a 2017 study demonstrate that suppression of caveolae-mediated transport in brain endothelial cells protects the integrity of the blood-brain barrier.

    The blood-brain barrier is a highly selective semi-permeable barrier made up of endothelial cells connected via tight junctions. This barrier separates the circulating blood from the brain’s extracellular fluid and prevents the entry of substances that may be neurotoxic. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

    The investigators' previous research showed that a critical player in blood-brain barrier function is Mfsd2a, a transmembrane protein found exclusively on the endothelial cells that line blood vessels on the barrier. Mfsd2a participates in lipid transport and is the sole means by which lysophospholipid DHA, the brain’s preferred form of DHA (a type of omega-3 fatty acid) is delivered to the brain.

    Using mice that carried a mutation that blocked Mfsd2a’s capacity to transport DHA, the investigators assessed blood-brain barrier function as well as caveolae formation and activity in the animals' brains. Then they compared the lipid composition of brain endothelial cells to lung epithelial cells, which lack Mfsd2a.

    They found that mice that lacked Mfsd2a function had leakier blood-brain barriers and greater caveolae formation and activity than normal mice. They also found that brain endothelial cells had higher lipid concentrations than lung epithelial cells. The most abundant lipid in the brain endothelial cells was DHA, which was found in concentrations that were two to five times higher.

    These findings suggest that Mfsd2a-mediated transport of lipids, particularly DHA, impairs caveolae activity, thereby preserving blood-brain integrity. Learn more about links between Mfsd2a, DHA, and brain health in this open-access peer-reviewed article by Dr. Rhonda Patrick..

  • Menopause accelerates epigenetic aging.

    Menopause, which typically occurs around the age of 52 years, is the cessation of a female’s menstrual cycle and signifies the loss of reproductive capacity. Evidence suggests that early menopause increases the risk for age-related disease and premature death. Findings from a 2016 study suggest that menopause accelerates epigenetic aging.

    Epigenetics is a biological mechanism that regulates gene expression (how and when certain genes are turned on or off). Diet, lifestyle, and environmental exposures can drive epigenetic changes throughout a person’s lifespan to influence health and disease. Epigenetic age is based on a person’s DNA methylation profile and strongly correlates with their chronological age. However, some exceptions exist. For example, the epigenetic ages of semi-supercentenarians (people who live to be 105 to 109 years old) are markedly younger than their chronological ages.

    The investigators analyzed the DNA methylation profiles of more than 3,100 women enrolled in four large observational studies (Women’s Health Initiative; InCHIANTI; Parkinson’s Disease, Environment, and Genes; and the National Survey of Health and Development) to identify links between epigenetic age and menopause. Their analysis was based on assessment of the biological age of cells taken from the women’s blood, saliva, and inner cheek. Because the age at which a female experiences menopause is heritable, they conducted a Mendelian randomization analysis to identify genetic links between age at menopause and epigenetic aging.

    They found that menopause markedly accelerated epigenetic aging. Females who experienced earlier natural menopause were more likely to have “older” blood than those who experienced later menopause, but females who had surgical menopause (a surgical procedure in which the ovaries are removed) had older blood and saliva than those who experienced natural menopause. Cells taken from the inner cheek of females who took menopausal hormone therapies were younger than those who did not take hormones. They also found that a particular gene variant that influences the age at which a female experiences menopause also influences age acceleration.

    These findings suggest that menopause accelerates epigenetic aging in females. The investigators conceded that their findings do not establish a cause-and-effect relationship, however. In a related study, researchers found that menopause-related sleep disorders, such as insomnia or poor sleep quality, contribute to the accelerated aging associated with menopause. Learn more about accelerated epigenetic aging in this episode featuring Dr. Steve Horvath.

  • Antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    Antibiotics are prescribed for a wide range of infectious diseases. In 2015, healthcare providers in the United States wrote nearly 270 million antibiotic prescriptions – more than 800 antibiotic prescriptions for every 1,000 people. Health experts estimate that 30 percent of these prescriptions were likely unnecessary. Findings from a new study suggest that antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    The study included approximately 15,000 midlife participants (average age, 55 years) enrolled in the Nurses’ Health Study II, an ongoing prospective cohort study of female nurses. The participants completed questionnaires regarding their general health, diet, lifestyle, and medication use during the previous four years, including antibiotic use and the reason for which the antibiotic was prescribed. The investigators categorized the participants' cumulative antibiotic use as none, one to 14 days, 15 days to two months, and two months or more. Participants also completed a battery of neuropsychological tests.

    The investigators found that participants who took antibiotics for at least two months over the previous four years were more likely to perform worse on neuropsychological tests than participants who did not take antibiotics. The influence of antibiotic use on neuropsychological test scores was roughly equivalent to three to four years of aging. These findings held true even after considering other factors that could influence cognitive function, including age and coexisting illnesses.

    These findings suggest that longer exposure to antibiotics in midlife negatively influences cognitive health, underscoring the importance of moderating antibiotic use in older adults. They also support findings from animal studies that suggest antibiotic use early in life alters neuropeptide signaling pathways that influence behavioral development. Learn more about the effects of antibiotic use in early life in this clip featuring Dr. Eran Elinav.

  • Lifelong exercise protects older adults from losing muscle mass and function with age.

    With age, muscles shrink in size and lose strength, a process called sarcopenia that can increase frailty and reduce the quality of life for older adults. In people with sarcopenia, muscle fibers contain fewer satellite cells (i.e., muscle stem cells) and progressively lose their connections to nerves, a process called denervation. Findings of a new report show that lifelong exercisers have more youthful muscles that resist denervation.

    Satellite cells are stem cells that proliferate, fuse together, and form the long tubular structures than comprise muscle fibers. Satellite cells are necessary for muscle repair and growth after exercise, a process called hypertrophy, due to their connection with cells that produce growth factors and deliver nutrients. Previous research demonstrates that exercise interventions that last several weeks can reverse muscle denervation in older adults with frailty; however, the preventive effects of lifelong exercise have yet to be investigated.

    The authors recruited 15 moderately active young men (average age, 26 years), 16 older men who were lifelong exercisers (average age, 73 years), and 15 older men who lived a sedentary lifestyle (average age, 73 years). On their first visit to the lab, participants completed a bout of heavy resistance training on only one side of their body so that the researchers could compare the effects of exercise and sedentary behavior in each person. The researchers also measured maximum muscle strength and body composition and collected a blood sample. Participants provided another blood sample two days and six days after the exercise challenge and provided a muscle biopsy sample six days after.

    Lifelong exercisers had muscles that were more resistant to fatigue during exercise compared to sedentary young and older adults. Compared with sedentary older adults, lifelong exercisers had more satellite cells in their muscles connected to type 2 myofibrils, which are important for fast-twitch muscle movement, but no difference in connection to type 1 slow-twitch myofibrils. Muscles from lifelong exercisers also expressed high levels of mRNA for acetylcholine receptors, which are necessary for preventing denervation.

    These results show that lifelong exercisers maintained a more youthful muscle profile due to increased connections with muscle- and nerve-supporting satellite cells. People who started life with a sedentary lifestyle can still reap the longevity-promoting benefits of exercise. Starting a new aerobic exercise habit, even at age 70, cuts heart disease death in half.

  • Routine hyperbaric treatment increased telomere length and reduced senescence in humans.

    With age, tissues lose their ability to function properly, leading to an increased risk of cancer, cardiovascular disease, and Alzheimer’s disease, among others. Cells become exhausted from replication over time and enter a state of senescence, meaning they will no longer reproduce because they are damaged. Findings of a new report demonstrate the ability of hyperbaric treatments to reduce the number of senescent immune cells.

    Hyperbaric (i.e., high air pressure) treatments use increased atmospheric pressure and oxygen content to enhance the total amount of oxygen dissolved in the body, accelerating wound healing. Some forms of routine hyperbaric therapy cause the body to react as if it were experiencing hypoxia (i.e., low blood oxygen), a phenomenon called the hyperoxic-hypoxic paradox. Although some of the hypoxia-associated effects of hyperbaric treatments, such as sirtuin activation, stem cell proliferation, mitochondrial biogenesis, and neurogenesis, are associated with longevity, the effects of hyperbaric therapy on cellular senescence are unknown.

    The authors recruited 35 participants aged 60 and older who did not have cognitive decline and lived independently. Participants completed 60 hyperbaric treatments distributed as five sessions per week for three months. Each session consisted of 90 minutes of breathing 100 percent oxygen at a pressure twice that of normal barometric pressure. The researchers collected blood samples at multiple time points to measure markers of senescence in peripheral blood mononuclear cells, which include T cell, B cells, monocytes, and natural killer cells.

    By the 30th hyperbaric treatment, participants experienced statistically significant increases in telomere length, a marker of reduced senescence rate, in T-helper cells, B cells, and natural killer cells. Following all 60 treatments, telomere length increased by 30 percent in T-helper cells, 38 percent in B cells, and 22 percent in natural killer cells. Demonstrating further benefit, hyperbaric treatment reduced the number of senescent T-helper cells by 12 percent and cytotoxic T cells by 11 percent after 60 sessions.

    These results show, for the first time in humans, that routine hyperbaric treatment reduced the rate of aging in immune cells. However, because this study utilized a small sample, reported large variations in the data, and did not contain a control group, these results must be replicated with future research before they can be fully interpreted.

  • Maintaining a systolic blood pressure of 120 or less may protect against dementia and cognitive decline. Nearly two-thirds of adults living in the United States have hypertension (high blood pressure), defined as having a systolic pressure of 130 or higher or a diastolic pressure of 80 or higher. Hypertension damages small blood vessels in the eyes, kidneys, and other tissues, increasing the risk for disease and dysfunction. A 2019 study found that intensive blood pressure control in patients with hypertension reduces the risk of developing small blood vessel damage-related white matter lesions in the brain.

    Intensive blood pressure control is an aggressive treatment protocol for hypertension that seeks to achieve a target systolic blood pressure goal of 120 or less. This differs from standard treatment protocols, which stipulate that within three months of starting medication therapy to reduce high blood pressure, a patient’s target pressures (systolic and diastolic) should be less than 140/90. After three months, the target pressures should be less than 130/80.

    White matter lesions are areas in the brain that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of small blood vessel disease and are considered a risk factor for dementia.

    The study involved 670 adults (average age, 67 years) who had hypertension. Roughly half of the participants underwent intensive blood pressure control treatment, while the other half underwent standard treatment. The investigators performed MRI scans of all participants at the beginning of the intervention and again about four years later.

    They found that participants who underwent intensive blood pressure control had fewer white matter lesions in their brains compared to those who underwent the standard treatment. Interestingly, those who underwent intensive treatment exhibited greater brain volume losses than those who underwent standard treatment, but this difference was not statistically significant.

    These findings suggest that intensive blood pressure control reduces white matter lesions in the brains of people with hypertension and support findings from a related study that demonstrated that intensive blood pressure control may reduce the risk of adverse cognitive outcomes.

    Hypertension is highly preventable with lifestyle modifications that involve diet and exercise. For example, dietary components, such as potassium and magnesiumquercetin and vitamin D lower blood pressure. Aerobic exercise also lowers blood pressure. Learn about other beneficial effects of aerobic exercise in our overview article.

  • From the article:

    Researchers from the Morrison laboratory discovered that forces created from walking or running are transmitted from bone surfaces along arteriolar blood vessels into the marrow inside bones. Bone-forming cells that line the outside of the arterioles sense these forces and are induced to proliferate. This not only allows the formation of new bone cells, which helps to thicken bones, but the bone-forming cells also secrete a growth factor that increases the frequency of cells that form lymphocytes around the arterioles. Lymphocytes are the B and T cells that allow the immune system to fight infections.

    When the ability of the bone-forming cells to sense pressure caused by movement, also known as mechanical forces, was inactivated, it reduced the formation of new bone cells and lymphocytes, causing bones to become thinner and reducing the ability of mice to clear a bacterial infection.

  • From the article:

    In a mouse model of ALS, the compound butyrate helped correct a gut microbiome imbalance and reduced gut leakiness – both symptoms of ALS. The treated mice lived also longer compared to mice that weren’t given butyrate.

    […]

    When the researchers fed the ALS-prone mice butyrate in their water, starting when the mice were 35 to 42 days old, the mice showed a restored gut microbiome profile and improved gut integrity. Butyrate-treated mice also showed improved neuromuscular function and delayed onset of ALS symptoms. Treated mice showed symptoms at 150 days old compared to control mice at about 110 days. Treated mice also lived an average 38 days longer than mice not given butyrate.

  • Some people appear to age slower (or faster) than others, exhibiting vastly different age-related physical changes and disease risks. Recognition of this biological phenomenon has given rise to the concept of biological age – a measure of a person’s physiological and functional state. Scientists use a variety of means to gauge biological age, including methylation markers, gray matter volume, and facial aging. Findings from a recent study suggest that retinas provide useful biomarkers in determining a person’s biological age.

    The retina is a thin, multicellular layer lining the rear, interior portion of the eye. It plays critical roles in the cascade of events involved in visual processing, converting the energy of photons of the visible light spectrum into biochemical signals and transmitting those signals to the brain. Poor retinal health is often an indicator of systemic illness, such as cardiovascular disease or nutritional deficiency.

    The authors of the study viewed more than 80,000 retinal images collected from adults (average age, 55 years) participating in the UK Biobank Study. They also collected information about the participants' demographics, lifestyles, and overall health. The researchers used deep learning, a type of machine learning that mimics the way humans learn, to analyze images of the retinas and assign a biological age, which they referred to as “retinal age.” Then they calculated the retinal age gap – the difference between retinal age and chronological age. Having a positive retinal age gap was reflective of an older-appearing retina; having a negative retinal age gap was reflective of a younger-appearing retina. Finally, the researchers looked at links between retinal age gap and all causes of premature death.

    They found that their machine learning model accurately predicted retinal age and chronological age to within 3.5 years. For every year of positive retinal age gap difference, the risk of premature death from any cause increased 2 percent. Having positive retinal age gaps greater than three years increased the risk of premature death from specific diseases (other than cardiovascular disease or cancer) by as much as 67 percent. These findings held true even after taking other factors into account, such as body weight, high blood pressure, or smoking.

    These findings suggest that retinal age, as predicted via deep learning, is a powerful predictor of biological age and premature death risk. Collecting retinal images is a low-cost, non-invasive procedure that may be beneficial in identifying people at risk for premature disease and death. Learn about other strategies for predicting biological age in our overview article on epigenetic aging clocks.

  • Neural tube defects (e.g., spina bifida, hydranencephaly) are a group of birth defects caused by incomplete development of the outer layers of the brain or spinal cord. Prenatal folate supplementation prevents an estimated 70 percent of neural tube defects, but additional therapies are needed. A recent report describes the relationship between maternal diabetes and abnormal cell aging in the fetal nervous system in mice.

    Previous research has demonstrated a relationship between maternal diabetes and the incidence of neural tube defects in mice; however, the mechanisms that drive this relationship are unknown. High blood glucose levels cause oxidative damage and promote cellular senescence, a state in which cells are not metabolically active and do not reproduce. Aging cells accumulate damage over time and become senescent. In adults, an excess of senescent cells can promote inflammation and disease. In the developing fetus, senescence is vital for tissue remodeling and the building of limbs and organs. However, inappropriate senescence may lead to abnormal development.

    The investigators used multiple mouse models in their study. In a first experiment, they used a strain of mice that develop diabetes and compared them to wild-type mice that are not predisposed to any disease. They injected pregnant females from both groups with either rapamycin, a compound that slows cellular aging by inhibiting the enzyme mTOR, or a placebo. In a second experiment, they used diabetic and non-diabetic strains of knockout mice, whose genomes do not contain the gene FoxO3a, a regulator of aging that may slow cellular senescence.

    Maternal diabetes increased the abundance of biomarkers of cellular senescence and DNA damage in the lining of the brain in offspring. Pregnant diabetic mice that were exposed to rapamycin had offspring with lower levels of senescence biomarkers and fewer neural tube defects compared to placebo. Offspring from FoxO3a knockout mice experienced the same decrease in senescence biomarkers and neural tube defect rates as rapamycin-treated mice.

    These results elucidate the mechanisms by which maternal diabetes can cause birth defects through metabolic changes that accelerate aging. Learn more about the role of cellular senescence in aging in this episode featuring Dr. Judith Campisi.

  • Declines in brain function are common with age owing to metabolic and immune alterations that include changes to the gut microbiota, the community of microorganisms that inhabit the intestines. While a diverse microbial community with many species of beneficial bacteria is associated with improved nutrition and reduced inflammation, older adults (especially residents of long-term care facilities) have perturbations in microbiota composition that increase the risk for cognitive decline and frailty. Findings of a report released this month show that fecal microbiota transplantation from young to aged mice reverses age-associated cognitive impairment.

    Fecal microbiota transplantation is a therapy in which microbes are isolated from the stool of a donor, processed, filtered, and administered to a recipient by nasogastric tube or enema. Previous research demonstrates the efficacy of fecal microbiota transplantation in treating infection with Clostridium difficile, a hospital-acquired infection that is difficult to treat with antibiotics, and a growing list of other diseases such as inflammatory bowel disease, metabolic syndrome, neurodevelopmental disorders (e.g., autism), and autoimmune diseases. Fecal microbiota transplantation improves health partially by increasing microbiota alpha diversity, meaning the number of species in an individual’s microbiota, also called “richess.” A microbiota with high richness is more likely to contain key beneficial species, such as those that produce neuroprotective short chain fatty acids.

    Given the wide range of diseases associated with gastrointestinal microbiota composition, its effects on aging are an area of intense interest. Prior investigations have demonstrated that transfer of the fecal microbiota from aged mice to young mice alters immunity, neurogenesis, and cognition; however, the consequence of fecal transplantation from young mice to aged mice is unknown.

    The investigators performed their experiment using young and aged male mice. They assigned aged mice to receive a fecal microbiota transplant from either a young mouse (the experimental group) or aged mouse (the control group). For further comparison, the researchers also assigned a group of young mice to receive a fecal microbiota transplant from another young mouse. Mice received the fecal microbiota transplant treatments once per day for three days, then twice weekly for four weeks. The mice completed a battery of tests to assess cognitive function. The researchers collected fecal samples in order to sequence the DNA of the microbiota and blood samples in order to measure hormones, cytokines, and other immune markers before and after the four weeks of treatment. Finally, they analyzed changes to gene expression and metabolism in the hippocampus, the brain region most-associated with age-related cognitive decline.

    At baseline, young and aged mice had distinctly different microbiota composition. Following four weeks of microbiota transplantation, young mice, aged mice receiving a young transplant, and aged mice receiving an aged transplant all had similar microbiota composition. Aged mice tended to have more over-reactive T cells, dendritic cells, and macrophages, especially in the lymph nodes that line the intestines. Aged mice also showed enlargement of microglia (the predominant immune cells in the brain), a common feature of neurodegenerative diseases. Microbiota transplantation from young mice reversed these age-related effects on brain and peripheral immunity. Amino acid metabolism in the hippocampus, which is necessary for neurotransmission and cognition, was impaired in aged mice, but restored following microbiota transplantation from young mice. Finally, the improved hippocampal metabolism in aged mice that received a young microbiota transplant translated to increased learning and long-term memory and reduced anxiety-related behaviors compared to aged mice receiving an aged microbiota transplant.

    These results reveal the potential benefits of fecal microbiota transplantation from young donors as a therapy to promote healthy aging.

  • Since the 1990s, longevity researchers have attempted to estimate the maximum human lifespan; however, supercentenarians (i.e., people who live beyond 110 years) routinely break these estimates. Additional research is needed to provide more accurate models of aging for use in planning government programs and economic policy. Authors of a paper released this year report their updated estimates for the maximum age at death in the year 2100.

    The existence of a fixed age limit for humans is an area of debate, with some scientists theorizing that biological processes like the shortening of telomeres are irreversible, determined by genetics, and a strong predictor of death. However, others argue that there is no limit to human lifespan and that age-related risk of death plateaus around 110 years of age. This uncertainty is partly due to a lack of consistent record keeping with verified age information. Research institutions have recently created systems such as the International Database on Longevity, a database containing validated supercentenarian life lengths from 15 countries, to aid in future research.

    The investigators used a statistical model created by the authors of a 2017 report on maximum lifespan. This model estimates the survival probability of supercentenarians, meaning the likelihood of surviving each year beyond age 110 years. For the current report, the researchers used updated data from the International Database on Longevity, which currently includes records from more than 1,100 supercentenarians and almost 14,000 semi-supercentenarians (people who live between 105 and 109 years). They also added additional projections to the model regarding future levels of fertility and life expectancy across multiple countries and extended the projection window to the year 2100.

    The authors found that the probability of breaking the current maximum reported age at death (122 years and 164 days, set by Jeanne Calment of France) this century is nearly 100 percent; the probability of a person reaching age 126 is approximately 89 percent; and the probability of a person reaching age 130 is nearly 13 percent. While the model did not exclude the possibility of a person living to 135 or 140 years this century, it is extremely unlikely. These estimates are in line with most other projections.

    The authors concluded that these data do not support the existence of a maximum human age and forecast substantial increases in the number of supercentenarians in the coming decades.

  • Sarcopenia, the loss of muscle mass with age, is related to falling, poor oral health, and chronic disease. Sarcopenia is a progressive disorder, but early interventions with diet and exercise may improve health outcomes. Authors of a new report investigated the relationship between sarcopenia progression, depression, dementia, and hypertension.

    Body composition shifts across the lifespan, with a progression toward lower muscle mass and increased fat mass after age of 60. Because fat and muscle participate in whole-body metabolism and hormone signaling, this shift in body composition contributes to the development of age-related diseases. Previous research has reported a link between sarcopenia, cognitive impairment, and depressive symptoms in older Korean men, but research is needed in additional demographic groups.

    The authors collected data from more than 750 adults aged 60 years and older living in Japan. Participants completed surveys to measure depression and dementia status and underwent a physical examination that included the measurement of blood pressure, height, muscle mass, grip strength, and walking speed. The investigators classified participants as having sarcopenia if they had low skeletal muscle index (i.e., the ratio of the muscle in a person’s arms and legs to their height), poor grip strength, and slower walking speed. They defined pre-sarcopenia as having a low skeletal muscle index with normal grip strength and walking speed. Finally, they classified participants with a normal skeletal muscle index as robust.

    Sarcopenia was associated with increased age and depression severity, but reduced hypertension. Compared to robust participants, those with pre-sarcopenia were more likely to have depression and hypertension. However, sarcopenia was not associated with dementia, which the authors noted may have been due to the small number of participants (only 49) with dementia.

    The authors suggested that future research should explore strategies for management of depression, dementia, and hypertension in the prevention of sarcopenia.

  • Semi-supercentenarians and supercentenarians – people who live to the age of 105 years and beyond – personify healthy aging, having avoided the diseases and concomitant disabilities that many adults experience, such as cardiovascular disease, diabetes, cancer, and cognitive decline. Genetics play key roles in longevity and healthy aging. Findings from a recent study indicate that semi-supercentenarians and supercentenarians have unique genetic profiles characterized by highly efficient DNA repair mechanisms.

    DNA repair is a cellular defense mechanism that helps maintain genomic integrity. Research had identified five DNA repair pathways, which are active throughout the varied stages of the cell cycle. Failure of these pathways contributes to genomic instability, a hallmark of many chronic diseases.

    The study involved 81 semi-supercentenarians (105 years or older) and supercentenarians (110 years or older) who were matched with 36 healthy adults (average age, 68 years) living in the same regions of Italy. Using blood samples collected from the participants, the investigators conducted whole-genome sequencing to identify genetic differences between the two groups and to create a risk score for cardiovascular disease, the leading cause of death worldwide. They compared their findings with those of a similar recent study.

    The authors of the study identified five genetic variants among the participants, some of which are involved in DNA repair, mitochondrial function, and elimination of reactive oxygen species – a driver of inflammation. The participants also had fewer naturally occurring mutations, potentially conferring a protective effect against many chronic diseases. They replicated their findings in the other study.

    These data suggest that people who live longer, healthier lives share similar genetic profiles that provide protection against many chronic diseases and promote healthy aging. Learn more about healthy aging in this episode featuring aging expert Dr. Judith Campisi.

  • Body mass index (BMI) is a measure of body size that is calculated by dividing a person’s weight by their height. A wealth of research has demonstrated that having a body mass index outside of the normal range (18.5 to 25) increases the risk of death. However, body mass index does not differentiate fat and muscle mass. Authors of a new report investigated the effects of body composition on risk of death.

    Extra body fat has been shown to increase the risk of developing a number of chronic lifestyle diseases, while increased muscle (fat-free) mass has been shown to decrease disease risk. Previous research has demonstrated mixed results for the effect of body composition and risk of death, likely due to differences in study design.

    The authors combined data from seven studies with over 16,000 participants between the ages of 20 and 93 years collected between 1994 and 2008. Researchers measured body composition using bioelectrical impedance and adjusted for age and sex. They also interviewed participants about their health, lifestyle, and socioeconomic factors and tracked them for an average of 14 years.

    After adjusting for a number of demographic and lifestyle factors, the researchers found that having body fat below or above the normal range increased risk of death among the participants. Those with high body fat (37 kilograms) had a 56 percent greater risk of death, while those with highest fat-free mass had a 30 percent lower risk of death.

    The authors concluded that fat mass and fat-free mass have opposite effects on the risk of death. They noted that their study included a large number of participants and a long follow-up period, which strengthened the quality of their results.

  • Brain derived neurotrophic factor (BDNF) is a growth factor associated with decreased risk of dementia and improved cognitive function in humans. While BDNF promotes brain cell growth plasticity, its precursor form, called proBDNF, has the opposite effect, promoting cell death. The authors of a recent report investigated the relationship between blood levels of pro-BDNF and memory loss.

    The effects of Alzheimer’s disease on the brain can be observed 10 to15 years before the onset of dementia, which presents the opportunity for early detection. Even though BDNF is known to cross the blood-brain barrier, whether blood levels of BDNF are reflective of BDNF activity in the brain is unclear. Establishing blood biomarkers of dementia risk provides the ability for early intervention.

    The authors recruited 256 older adults (average age, 68 years) without dementia. They analyzed magnetic resonance imaging (MRI) scans of the participants’ brains and measured blood levels of BDNF and proBDNF. Participants completed questionnaires to measure memory and physical activity habits.

    The investigators reported that increased age and decreased physical activity were associated with poorer memory performance. MRI findings showed decreased volume in the hippocampus, the region of the brain associated with memory, in those with worse memory scores. Finally, the authors reported that decreased blood levels of BDNF, but not pro-BDNF, were associated with worse memory performance.

    These results echo earlier findings that exercise is associated with greater BDNF activity and better memory performance. The authors conclude the measuring blood levels of BDNF may be an effective strategy for early detection of dementia.

  • Cellular senescence is the condition or process of cellular deterioration that occurs with age. Senescent cells often release inflammatory proteins that can damage neighboring healthy cells. Understanding the genetic and epigenetic bases of cellular senescence is instrumental in developing interventions to slow aging. A recent report identifies a gene therapy strategy to slow aging in mice.

    Gene therapy is a technique in which altered (mutated) genes are corrected as a means to prevent or treat disease. One type of gene therapy involves inactivating a mutated gene that is functioning improperly.

    The study investigators conducted a genome-wide screen of mesenchymal precursor cells (a descendant of embryonic stem cells) that carried genes for Werner syndrome and Hutchinson-Gilford progeria syndrome – conditions characterized by rapid, accelerated aging. They found that the primary driver of the accelerated aging in both syndromes was KAT7, an enzyme involved in histone modification.

    Then the investigators inactivated the KAT7 gene in normally aging mice and prematurely aging mice and found that inactivation of the gene extended the animals' lifespan. They did not observe any toxicities or adverse events in the animals.

    These findings suggest that inactivation of critical genes involved in aging syndromes extends lifespan in mice and shows promise as a strategy to slow aging in humans.

  • From the article:

    For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer’s disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.

    In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer’s disease.

    […]

    “In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment.”

  • As the human body ages several changes occur, including the gradual erosion of the protective caps on the ends of chromosomes, known as telomeres. A 2012 study suggests that supplementing with omega-3 fatty acids can counteract telomere shortening and slow aging.

    Telomeres function as a protective buffer against DNA loss during replication and DNA damage caused by inflammation, reactive oxygen species, and other chemical compounds. Telomeres get shorter with age and telomere length is a biological marker for age.

    Previous research has demonstrated that many factors can affect the rate of telomere shortening. The dietary balance of the essential polyunsaturated fatty acids (PUFAs) omega-3 and omega-6 — which influence inflammation — might be a factor. The current study investigated whether blood levels of these polyunsaturated fatty acids affect telomere stability.

    The double-blind randomized controlled trial involved 106 adults between the ages of 40 and 85 years who were sedentary and overweight. The authors of the study provided participants with a supplement containing 1.25 grams or 2.5 grams of omega-3 fatty acids or a placebo. To evaluate the influence of the omega-3 fatty acids versus placebo, the authors measured telomere length, telomerase activity, and markers of oxidative stress (known as F2-isoprostanes). They found that supplementation at both doses lowered the omega-6 to omega-3 fatty acid ratio in the blood, which was associated with longer telomere length. They also observed that omega-3 fatty acid supplementation decreased markers of oxidative stress by 15 percent.

    These findings suggest that consumption of omega-3 fatty acids in quantities high enough to lower the omega-6 to omega-3 ratio in the blood can slow aging.

  • Cardiovascular disease is a broad class of diseases that involve the heart or blood vessels, including stroke, hypertension, thrombosis, heart failure, and atherosclerosis. As much as 90 percent of cardiovascular disease may be attributable to lifestyle factors and, therefore, preventable. A recent study found that having better cardiovascular health during one’s midlife years may reduce risk of premature death later in life.

    The American Heart Association has developed a scoring system that describes a person’s cardiovascular health based on measures of various lifestyle behaviors, such as smoking, diet, and physical activity, and known cardiovascular disease risk factors, such as blood pressure, body mass index, and blood glucose and cholesterol levels. Having a higher cardiovascular health score is associated with reduced markers of disease, longer telomeres, and better vascular function and, consequently, lower risk of cardiovascular disease, diabetes, and premature death.

    The prospective cohort study, which spanned a 16-year period, drew on data from the Framingham Heart Study Offspring investigation and involved 1,445 men and women whose average age was 60 years. The authors of the study found that for every five-year period that a person had intermediate or ideal cardiovascular health, they had a 33 percent lower risk for high blood pressure, 27 percent lower risk for diabetes or cardiovascular disease, 25 percent lower risk for diabetes, and 14 percent lower risk for premature death, compared to people who were in poor cardiovascular health. These findings held true regardless of age or sex.

    Sauna use is a lifestyle behavior that has been shown to improve cardiovascular health. A large study of health outcomes in more than 2,300 middle-aged men from eastern Finland identified strong, dose-dependent links between sauna use and reduced cardiovascular-related death and disease. Compared to men who used the sauna once weekly, men who used the sauna four to seven times per week were 50 percent less likely to die from cardiovascular-related causes. Watch this clip in which Drs. Rhonda Patrick and Jari Laukkanen discuss these findings.