Aging leads to a gradual decline in kidney function, making the kidneys increasingly vulnerable to various diseases. Oxidative stress, together with cellular senescence, has been established as paramount in promoting the aging process of the kidney. Oxidative stress, defined as an imbalance between ROS formation and antioxidant defense mechanisms, has been implicated in the kidney's cellular injury, inflammation, and premature senescence. Concurrently, the accumulation of SCs in the kidney also exacerbates oxidative stress via the secretion of pro-inflammatory and tissue-damaging factors as the senescence-associated secretory phenotype (SASP). Recently, SIRT1, a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, has been pivotal in combating oxidative stress and cellular senescence in the aging kidney. SIRT1 acts as a potential antioxidant molecule through myriad pathways that influence diverse transcription factors and enzymes essential in maintaining redox homeostasis. SIRT1 promotes longevity and renal health by modulating the acetylation of cell cycle and senescence pathways. This review covers the complex relationship between oxidative stress and cellular senescence in the aging kidney, emphasizing the protective role of SIRT1. See also the graphical abstract(Fig. 1).
Keywords: SASP; SIRT1; cellular senescence; homeostasis; oxidative stress.
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