Targeting Cellular Senescence in Kidney Aging with Traditional Chinese Medicine: Potential Senolytic and Senomorphic Strategies.

Abstract

Cellular senescence, a key driver of kidney aging and functional decline, manifests in 2 primary forms: (1) replicative senescence, primarily caused by telomere shortening; and (2) stress-induced senescence, triggered by factors such as oxidative stress and DNA damage. Senescent cells are characterized by permanent cell cycle arrest, activation of senescence-associated secretory phenotype (SASP), and epigenetic alterations, among others. It is important to note that cellular senescence is not exclusively detrimental; it also serves necessary, programmed functions in physiologic tissue remodeling and tumor suppression. However, its chronic accumulation with age is a major driver of organ decline. Currently, specific treatments targeting senescent cells are lacking. Strategies to counteract senescent cells fall into 2 main categories: (1) senolytics, which eliminate senescent cells; and (2) senomorphics, which mitigate their detrimental paracrine effects, including SASP inhibitors. Traditional Chinese Medicine (TCM) has demonstrated potential in combating aging through both senolytic and senomorphic mechanisms. Current evidence suggests that several TCM-derived compounds and formulations may modulate renal senescence-related pathways, including BCL-2 family-dependent apoptosis resistance, NF-κB/JAK2-STAT3/NLRP3-mediated SASP, NOX4-ROS/Nrf2 oxidative stress signaling, AMPK/mTOR/SIRT1 nutrient-sensing pathways, Klotho expression, and the gut-kidney axis. This review explores the emerging role of TCM in addressing renal aging, highlighting its advantages as a multi-targeted, low-toxicity therapeutic strategy to mitigate aging-related kidney diseases.