The death rate from all causes of death for a population in a given time period.

A molecule that inhibits oxidative damage to DNA, proteins, and lipids in cells. Oxidative damage plays a role in the aging process, cancer, and neurodegeneration. Many vitamins and plant-based compounds are antioxidants.

The shrinking or wasting away of cells, organs, or tissues that may occur as part of a disease process, trauma, or aging.

A developmental disorder characterized by impaired social interaction, behavioral problems, and poor communication. Autism typically manifests in early childhood and is slightly more common among boys than girls. In clinical trials, sulforaphane, a compound derived from broccoli and broccoli sprouts, reduces the characteristic behaviors associated with autism.

The extent and rate at which drugs or other substances, such as plant-based dietary compounds, enter the body’s circulation. Bioavailability is influenced by a variety of factors, including dose, the presence of other foods or substances, and interindividual differences in metabolism due to gut absorptive surface and commensal microbial populations.

A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.

A wavelength of light emitted from natural and electronic sources. Blue light exposure is associated with improved attention span, reaction time, and mood. However, exposure to blue light outside the normal daytime hours may suppress melatonin secretion, impairing sleep patterns. In addition, blue light contributes to digital eye strain and may increase risk of developing macular degeneration.

A commonly occurring metal element. Cadmium is used in batteries, alloys, electroplated coatings, solar cells, plastics, and pigments. Cadmium and its related compounds are carcinogenic and target the body’s cardiovascular, renal, gastrointestinal, neurological, reproductive, and respiratory systems. Exposure to cadmium typically occurs via food, cigarettes, second-hand smoke, or emissions from fossil fuels.

A medication used to prevent and to treat malaria. It is also occasionally used for amebiasis that is occurring outside of the intestines, rheumatoid arthritis, and lupus erythematosus. Currently it is being researched as an antiretroviral in humans with HIV-1/AIDS, an agent in chemotherapy for cancer, and its ability to inhibit lysosomal degradation of protein products during autophagy.

A waxy lipid produced primarily in the liver and intestines. Cholesterol can be synthesized endogenously and is present in all the body's cells, where it participates in many physiological functions, including fat metabolism, hormone production, vitamin D synthesis, and cell membrane integrity. Dietary sources of cholesterol include egg yolks, meat, and cheese.

Proteins that preserve cell viability at low temperatures by binding to nucleic acids and, subsequently, controlling gene expression. Cold shock proteins have what is known as a "cold-shock domain," a sequence of amino acids whose expression is associated with cold and is thought to help cells survive in lower than optimal temperatures.

In statistics, a confounder (also confounding variable or confounding factor) is a variable that is correlated (directly or inversely) to both the dependent variable and independent variable.

A variable that is related to one or more of the other variables in a study. A confounding factor can mask an association that exists between variables or demonstrate an association that does not exist. If confounding factors are not measured and considered, the findings of the study may be biased.

A steroid hormone that participates in the body’s stress response. Cortisol is a glucocorticoid hormone produced in humans by the adrenal gland. It is released in response to stress and low blood glucose. Chronic elevated cortisol is associated with accelerated aging. It may damage the hippocampus and impair hippocampus-dependent learning and memory in humans.

An infectious disease caused by the novel coronavirus SARS-CoV-2. COVID-19, or coronavirus disease 2019, was first identified in Wuhan, China, in late 2019. The disease manifests primarily as a lower respiratory illness, but it can affect multiple organ systems, including the cardiovascular, neurological, gastrointestinal, and renal systems. Symptoms include fever, cough, fatigue, shortness of breath, and loss of smell and taste. Some infected persons, especially children, are asymptomatic. Severe complications of COVID-19 include pneumonia, sepsis, acute respiratory distress syndrome, kidney failure, multiple organ dysfunction syndrome, and cytokine storm. Treatments currently involve symptom management and supportive care. Mortality varies by country and region, but approximately 6 percent of people living in the United States who are diagnosed with COVID-19 expire.[1] 1

Cooling of the body for therapeutic purposes. Cryotherapy can include the use of products such as ice packs on a localized portion of the body, such as a joint or muscle, or whole body exposure to extremely low temperatures in water or air. Cryotherapy has profound effects on many parts and functions of the body, including the brain, immune system, and metabolism, among others.

A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.

A general term referring to cognitive decline that interferes with normal daily living. Dementia commonly occurs in older age and is characterized by progressive loss of memory, executive function, and reasoning. Approximately 70 percent of all dementia cases are due to Alzheimer’s disease.

A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.

A vitamin that is readily dissolved in fats or oils. Fat-soluble vitamins are absorbed along with fats in the diet and can be stored in the body’s fatty tissue. Vitamins A, D, E, and K are fat-soluble. Dietary sources of fat-soluble vitamins include fatty fish (such as salmon), nuts, oils, and avocados, among others.

Flavonoid are widely distributed in plants, fulfilling many functions. Flavonoids have been shown to have a wide range of biological and pharmacological activities in animal, human, and in-vitro studies. Examples include anti-allergic, anti-inflammatory, antioxidant, antimicrobial, anti-cancer, and anti-diarrheal activities.

An antioxidant compound produced by the body’s cells. Glutathione helps prevent damage from oxidative stress caused by the production of reactive oxygen species.

A family of proteins produced by cells in response to exposure to stressful conditions. Heat shock proteins are expressed in response to heat as well as exposure to cold and UV light, and during wound healing and tissue remodeling. Many heat shock proteins function as chaperones by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by cell stress. A 30-minute 73ºC sauna session in healthy young adults has been shown to cause a robust and sustained increase in the production of heat shock proteins for up to 48 hours afterward.^[1]

An organism’s ability to maintain its internal environment within defined limits that allow it to survive. Homeostasis involves self-regulating processes that return critical bodily systems to a particular “set point” within a narrow range of operation, consistent with the organism’s survival.

High blood pressure. Hypertension, defined as a systolic pressure of 130 mm Hg or higher, or a diastolic pressure of 80 mm Hg or higher, is a robust predictor of future incidence of stroke, coronary heart disease, heart attack, heart failure, and cardiovascular-related death. Central to the pathophysiology of hypertension is the loss of arterial compliance, which can have far-reaching effects on multiple organ systems, including the brain and kidneys.

A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.

A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.

A hormone that regulates the sleep-wake cycle in mammals. Melatonin is produced in the pineal gland of the brain and is involved in the expression of more than 500 genes. The greatest influence on melatonin secretion is light: Generally, melatonin levels are low during the day and high during the night. Interestingly, melatonin levels are elevated in blind people, potentially contributing to their decreased cancer risk.^[1]

The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.

The collection of genomes of the microorganisms in a given niche. The human microbiome plays key roles in development, immunity, and nutrition. Microbiome dysfunction is associated with the pathology of several conditions, including obesity, depression, and autoimmune disorders such as type 1 diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and fibromyalgia.

The process of forming new neurons. Neurogenesis is essential during embryonic development, but also continues in certain brain regions throughout human lifespan.

The brain's ability to reorganize itself by forming new neural connections throughout life. Neuroplasticity allows the neurons (nerve cells) in the brain to compensate for injury and disease and to adjust their activities in response to new situations or to changes in their environment.

A type of white blood cell, also known as a granulocyte. Neutrophils are the most abundant form of blood cell, comprising approximately 60 percent of total cells. They ingest, kill, and digest microbial pathogens, and are the first cells recruited to acute sites of injury. Neutrophils can infiltrate brain structures, driving inflammation and increasing the risk for neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease.

A substance produced in the brain. Norepinephrine acts as a hormone and neurotransmitter and is best known for its role in the body’s “fight or flight” response to stress. Its role as a neurotransmitter has been exploited as a molecular target for a class of drugs known as norepinephrine reuptake inhibitors, which were developed for the purpose of treating disorders ranging from ADHD to narcolepsy and depression. Norepinephrine also plays a role in converting white adipose tissue into brown adipose tissue via an uncoupling protein 1 (UCP-1) mediated mechanism.

One of four nitrogen-containing molecules that comprise DNA. A nucleotide consists of one of four chemicals, called a “base,” plus one molecule of sugar and one molecule of phosphoric acid. Nucleotides are typically identified by the first letter of their base names: adenine (A), cytosine (C), guanine (G), and thymine (T). They form specific pairs (A with T, and G with C), and their bonds provide the helical structure of the DNA strand.

A naturally-occurring substance found in many foods. Oxalate binds to calcium in the gut and is eliminated in the feces. Any unbound oxalate passes through the kidneys and is excreted in the urine. High levels of oxalate in the kidneys can contribute to the risk of developing kidney stones. Dietary sources of oxalate include dark green leafy vegetables, beans, potatoes, and bran, among others.

Highly reactive molecules that have the ability to oxidize other molecules and cause them to lose electrons. Common oxidants are oxygen, hydrogen peroxide, and superoxide anion.

A chemical reaction in which an atom, molecule, or ion loses one or more electrons. Oxidation of biological molecules is associated with oxidative stress, a key driver of many chronic diseases.

In general, anything that can produce disease. Typically, the term is used to describe an infectious agent such as a virus, bacterium, prion, fungus, or other microorganism.

The movement of a drug or other xenobiotic substance into, through, and out of the body. Pharmacokinetics comprises absorption, distribution, metabolism, and excretion, often abbreviated "ADME." Many factors influence pharmacokinetics, including a person's age, gut health, and circadian rhythms, as well as the substance's bioavailability.

A medication or treatment intended for the prevention of disease.

Any enzyme that breaks down a protein into smaller subunits. Proteases can be found in Animalia, Plantae, Fungi, Bacteria, Archaea, or viruses.

A bioactive compound found in many edible plants. Quercetin demonstrates a wide range of health-promoting characteristics, including antioxidant, anti-inflammatory, and anti-cancer properties. It scavenges reactive oxygen and nitrogen species, inhibits activation of the proinflammatory molecule nuclear factor kappa B (NF-κB), and downregulates the inflammatory response of macrophages. When used in conjunction with the chemotherapy drug dasatinib, quercetin shows promise as a senolytic (anti-aging) compound, effectively clearing senescent cells and promoting improvements in a variety of age-related diseases. Dietary sources of quercetin include onions (most abundant), apples, berries, leafy vegetables, herbs, spices, legumes, tea, and cocoa.

A study in which people are randomly allocated to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. The control may be a standard practice, a placebo, or no intervention at all.

Senescence is a response to stress in which damaged cells suspend normal growth and metabolism. While senescence is vital for embryonic development, wound healing, and cancer immunity, accumulation of senescent cells causes increases inflammation and participates in the phenotype of aging.

Refers to small molecules that can selectively induce death of senescent cells. From the words "senescence" (the condition or process of deterioration with age) and "lytic" (destroying).

The body's overwhelming and life-threatening response to an infection which can lead to tissue damage, organ failure, and death.

A person who works on a schedule outside the traditional 9 AM – 5 PM day. Work can involve evening or night shifts, early morning shifts, and rotating shifts. Many industries rely heavily on shift work, and millions of people work in jobs that require shift schedules.

A sleep disorder characterized by repeated interruptions in breathing during sleep, reducing oxygen levels and disrupting sleep patterns. Two primary types of apnea have been identified: obstructive sleep apnea (OSA, caused by airway blockage) and central sleep apnea (CSA, caused by the brain's failure to signal breathing). Sleep apnea causes brain hypoxia and has been associated with an increased risk of many serious health conditions, including hypertension, cardiovascular disease, diabetes, depression, and stroke.^[1]

A diagnostic tool used in sleep medicine. During a sleep study, a person’s brain activity, eye movements, muscle activity, and heart rhythm are recorded. Sleep studies can determine quality of sleep and identify sleep disorders, such as apnea.

The primary male sex hormone. Testosterone is critical to the maintenance of fertility and secondary sexual characteristics in males. Low testosterone levels may increase risk of developing Alzheimer’s disease.

A metabolic disorder characterized by high blood sugar and insulin resistance. Type 2 diabetes is a progressive condition and is typically associated with overweight and low physical activity. Common symptoms include increased thirst, frequent urination, unexplained weight loss, increased hunger, fatigue, and impaired healing. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, diabetic retinopathy (and subsequent blindness), kidney failure, and diminished peripheral blood flow which may lead to amputations.

A compound, CO(NH2)2, occurring in urine and other body fluids as a product of protein metabolism.

A fat-soluble vitamin. Vitamin A is a collective term that includes retinol, retinal, and retinyl esters. Vitamin A plays key roles in immune function, reproduction, and cellular communication. It is best known for its role in supporting eye health and the processes involved in vision. Vitamin A also supports cell growth and differentiation and participates in the normal formation and maintenance of the heart, lungs, kidneys, and other organs. Dietary sources of vitamin A include liver, fish oils, milk, eggs, leafy green vegetables, orange and yellow vegetables, tomato products, fruits, and some vegetable oils.

A potent water-soluble antioxidant found in citrus fruits. Vitamin C is an essential nutrient involved in tissue repair, neurotransmission, and immune system function. Also known as ascorbic acid.

A fat-soluble vitamin stored in the liver and fatty tissues. Vitamin D plays key roles in several physiological processes, such as the regulation of blood pressure, calcium homeostasis, immune function, and the regulation of cell growth. In the skin, vitamin D decreases proliferation and enhances differentiation. Vitamin D synthesis begins when 7-dehydrocholesterol, which is found primarily in the skin’s epidermal layer, reacts to ultraviolet light and converts to vitamin D. Subsequent processes convert D to calcitriol, the active form of the vitamin. Vitamin D can be obtained from dietary sources, too, such as salmon, mushrooms, and many fortified foods.

A type of fat-soluble vitamin that participates in blood clotting and bone metabolism. Naturally occurring forms of vitamin K include phylloquinone (vitamin K1) and a family of molecules called menaquinones (vitamin K2). Vitamin K1 is synthesized by plants and is the major form present in the diet. Vitamin K2 molecules are synthesized by the gut microbiota and found in fermented foods and some animal products (especially liver). The body has limited vitamin K storage capacity, so the body recycles it in a vitamin K redox cycle and reuses it multiple times.

A type of fat-soluble vitamin. Vitamin K is critical for blood clotting, bone metabolism, prevention of blood vessel mineralization, and regulation of various cellular functions. Naturally occurring forms of vitamin K include phylloquinone (vitamin K1) and a family of molecules called menaquinones (vitamin K2). Vitamin K1 is synthesized by plants and is the major form in the diet. Vitamin K2 molecules are synthesized by the gut microbiota and found in fermented foods and some animal products (especially liver). The body has limited vitamin K storage capacity, so the body recycles it in a vitamin K redox cycle and reuses it multiple times.