Targeting Senescent Cells to Improve Human Health
The number of people reaching old age is expected to increase dramatically, and concomitantly age-related diseases, such as diabetes, chronic kidney disease, cardiovascular disease, cancer and neurodegenerative disorders. To improve health and quality of life at more advanced ages, it will be necessary to identify and characterize the molecular pathways and events that drive aging and aging-associated diseases. It was proposed that cellular senescence contributes to age-related pathologies, but definitive evidence has long been lacking. However, recent studies on BubR1 hypomorphic mice, which model a human progeroid syndrome referred mosaic variegated aneuploidy (MVA) syndrome, provide strong in vivo evidence senescent cells are causally implicated in aging-associated phenotypes and demonstrate that selective elimination of senescent cells can delay age-related tissue deterioration. These studies identify senescent cells and the senescence-associated secretory phenotype (SASP) they produce, as therapeutic targets for treatment of age-related disease and tissue/organ dysfunction. Here, we describe the formation and features of senescent cells, the evidence that cellular senescence drives age-related dysfunction, the accumulation of senescent cells at sites of pathology in chronic diseases, and potential therapeutic approaches specifically directed against senescent cells to improve human health.
KeywordsCellular senescence Senescence-associated secretory phenotype (SASP) Aging Age-related diseases Senotherapeutics Healthspan Longevity
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