Ageing, cellular senescence and chronic kidney disease: experimental evidence.
Huishi Tan, Jie Xu, Youhua Liu
Author Information
Huishi Tan: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jie Xu: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Youhua Liu: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
PURPOSE OF REVIEW: Chronic kidney disease (CKD) is often viewed as an accelerated and premature ageing of the kidney, as they share common pathological features characterized by cellular senescence. In this review, we summarize the experimental evidence linking cellular senescence to the pathobiology of kidney ageing and CKD, and discuss the strategies for targeting senescent cells in developing therapeutics for ageing-related kidney disorders. RECENT FINDINGS: Kidney ageing and CKD are featured with increased cellular senescence, an irreversible state of cell cycle arrest and the cessation of cell division. Senescent cells secrete a diverse array of proinflammatory and profibrotic factors known as senescence-associated secretory phenotype (SASP). Secondary senescence can be induced by primary senescent cells via a mechanism involving direct contact or the SASP. Various senolytic therapies aiming to selectively remove senescent cells in vivo have been developed. Senostatic approaches to suppress senescence or inhibit SASP, as well as nutrient signalling regulators are also validated in animal models of ageing. SUMMARY: These recent studies provide experimental evidence supporting the notion that accumulation of senescent cells and their associated SASP is a main driver leading to structural and functional organ degeneration in CKD and other ageing-related disorder.
