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.