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Targeting Cellular Senescence in Kidney Aging with Traditional Chinese Medicine: Potential Senolytic and Senomorphic
Jian Li1, Yuqing Li1, Yuan Liu2
1Department of Nephrology, Institute of Kidney Diseases, West China Hospital, Sichuan University, Chengdu, China.
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.
Insights
Cellular senescence drives kidney aging. Traditional Chinese Medicine (TCM) offers potential senolytic and senomorphic strategies to combat age-related kidney decline by targeting key aging pathways.
Area of Science:
- Gerontology and Nephrology
- Cellular Biology and Aging
- Integrative and Traditional Medicine
Background:
- Cellular senescence, characterized by cell cycle arrest and the senescence-associated secretory phenotype (SASP), is a primary driver of kidney aging and functional decline.
- Senescence arises from replicative stress (telomere shortening) or external factors (oxidative stress, DNA damage), contributing to organ aging despite beneficial roles in tissue remodeling and tumor suppression.
- Current therapeutic strategies for senescent cells include senolytics (elimination) and senomorphics (mitigation of SASP), but targeted treatments for age-related kidney disease remain limited.
Purpose of the Study:
- To review the emerging role of Traditional Chinese Medicine (TCM) in addressing renal aging.
- To explore TCM's potential as a multi-targeted, low-toxicity therapeutic strategy for mitigating age-related kidney diseases.
- To highlight TCM's senolytic and senomorphic mechanisms in combating cellular senescence in the kidney.
Main Methods:
- Literature review of current evidence on cellular senescence, renal aging, and TCM.
- Analysis of TCM-derived compounds and formulations modulating key renal senescence pathways.
- Exploration of TCM's impact on pathways including BCL-2, NF-κB, JAK2-STAT3, NLRP3, NOX4-ROS, Nrf2, AMPK, mTOR, SIRT1, Klotho, and the gut-kidney axis.
Main Results:
- TCM demonstrates potential senolytic and senomorphic effects relevant to kidney aging.
- Several TCM compounds and formulations can modulate critical pathways implicated in renal senescence and aging.
- TCM targets multiple aging mechanisms, including apoptosis resistance, SASP, oxidative stress, nutrient sensing, and the gut-kidney axis.
Conclusions:
- TCM offers a promising, multi-faceted approach to counteract cellular senescence and mitigate age-related kidney diseases.
- The low-toxicity and multi-targeted nature of TCM presents advantages over conventional therapies for renal aging.
- Further research into TCM mechanisms and clinical applications is warranted to combat age-related kidney decline.
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