Emily Lo

Introduction: Cellular senescence is a cell stage associated with DNA damage in which a cell can no longer replicate and gains resistance to apoptosis¹. Senescent cells secrete an array of inflammatory cytokines and chemokines, including TNF-alpha, IL-6, and IL-8¹. Accumulation of senescent cells and their associated inflammation is thought to be a driver of many age-associated diseases including type 2 diabetes, Alzheimer’s, Parkinson’s, and cancer¹. Moreover, other studies have shown that increasing senescent cell load also decreases physical ability². Here, we review studies testing the hypothesis that removing senescent cells by senolytic agents can decrease inflammation, increase physical ability, and increase lifespan without extending morbidity in mice models². Methods. Mice were injected with either control or senescent luminescent preadipocytes. Each group was then either treated with a senolytic agent or with vehicle. Mice were imaged to evaluate luminescence as a measure of remaining control and senescent cells. In another experiment, mice were allowed to age naturally and were either treated with senolytic agent or vehicle every two weeks for four months. At the end of the treatment cycle, mice were evaluated for cytokine expression, physical function, and lifespan. Results. Treatment with senolytic agents following a senescent cell transplant resulted in a reduction of senescent cells. Treatment with senolytic agents in naturally aged mice resulted in improved survival rate along with a reduction in expression of inflammatory cytokines IL-6, Mcp-1, Cxd-1, and p16. The naturally aged mice treated with senolytic agents also displayed an improvement in maximal speed, hanging endurance, grip strength, treadmill endurance, and daily activity. Conclusion. Our studies clearly show that removal of senescent cells can reduce inflammation and physical disability associated with aging, leading to healthier aging and an increase in lifespan in mice. As the world population continues to age, treatment of age-related diseases will dominate medicine and removal of senolytic cells may serve as a method to promote healthier aging and decrease the burden of age-related pathologies.

1. Zhu X, Chen Z, Shen W, et al. Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduction and Targeted Therapy. 2021;6(1). doi:10.1038/s41392-021-00646-9
2. Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age. Nature Medicine. 2018;24(8):1246-1256. doi:10.1038/s41591-018-0092-9