Vascular Tissue Challenge Announcement Removal of Senescent Cells Prevents Early Deaths Β2-microglobulin, a Circulating Pro-aging Factor Lanosterol and Cataracts

Cellular senescence, a stress -induced irreversible growth arrest often characterized by expression of p16 Ink 4a (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of pre -neoplastic cells and has beneficial roles in t issue remodeling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over t ime, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of n aturally occurring senescent cells , here we use a previously established transgene, INK -ATTAC, to induce apoptosis in p16Ink4a expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to veh icle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a positive cells delayed tumorigenesis and attenuated age -related deterioration of several organs without apparent s ide effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16Ink4a-positive cells that accumulate during adulthood negatively influence l ifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.