Oxidative stress and senescence in aging kidneys: the protective role of SIRT1

Abstract

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.

Table 1. This table summarizes various studies on the role of SIRT1 in renal health, highlighting the models used, mechanisms involved, effects on oxidative stress and SIRT1 activation, and potential therapeutic implications. It provides a concise overview of how targeting SIRT1-related pathways may mitigate kidney aging and disease

Table 2. This table summarizes various compounds and agents studied for their effects on renal aging, detailing their mechanisms, key findings, and therapeutic implications. Each entry includes SIRT1 modulation and oxidative stress reduction.

Figure 1. Graphical abstract

Figure 2. The image illustrates the process of kidney aging, highlighting key factors such as telomere aging, inflammation and oxidative stress, mitochondrial dysfunction, ER stress, and fibrosis. Each factor contributes to the overall decline in kidney function associated with aging.

Figure 3. The image illustrates the pathway of cell apoptosis in aging and aging-associated kidney disorders, involving DNA damage and PARP activation, leading to NAD+ and ATP depletion. SIRT deacetylates P53, regulating apoptotic mediators, while DNA repair mechanisms attempt to restore cell health, preventing apoptosis.

Figure 4. The image illustrates the protective role of SIRT1 in preventing kidney injury from severe burns. Melatonin activates SIRT1, which deacetylates p53 and p65, reducing apoptosis and inflammation. SIRT1 also enhances FOXO1 activity, mitigating oxidative stress and kidney damage.