Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors.

Seyyedeh Mina Hejazian, Seyyed Sina Hejazian, Seyyedeh Mina Mostafavi, Seyed Mahdi Hosseiniyan, Soheila Montazersaheb, Mohammadreza Ardalan, Sepideh Zununi Vahed, Abolfazl Barzegari

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. · pubmed

Paper

Abstract

Cellular senescence is a phenomenon distinguished by the halting of cellular division, typically triggered by DNA injury or numerous stress-inducing factors. Cellular senescence is implicated in various pathological and physiological processes and is a hallmark of aging. The presence of accumulated senescent cells, whether transiently (acute senescence) or persistently (chronic senescence) plays a dual role in various conditions such as natural kidney aging and different kidney disorders. Elevations in senescent cells and senescence-associated secretory phenotype (SASP) levels correlate with decreased kidney function, kidney ailments, and age-related conditions. Strategies involving senotherapeutic agents like senolytics, senomorphics, and senoinflammation have been devised to specifically target senescent cells. Mesenchymal stem cells (MSCs) and their secreted factors may also offer alternative approaches for anti-senescence interventions. The MSC-derived secretome compromises significant therapeutic benefits in kidney diseases by facilitating tissue repair via anti-inflammatory, anti-fibrosis, anti-apoptotic, and pro-angiogenesis effects, thereby improving kidney function and mitigating disease progression. Moreover, by promoting the clearance of senescent cells or modulating their secretory profiles, MSCs could potentially reverse some age-related declines in kidney function.This review article intends to shed light on the present discoveries concerning the role of cellular senescence in kidney aging and diseases. Furthermore, it outlines the role of senotherapeutics utilized to alleviate kidney damage and aging. It also highlights the possible impact of MSCs secretome on mitigating kidney injury and prolonging lifespan across various models of kidney diseases as a novel senotherapy.

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Research summary

The paper addresses cellular senescence, a key factor in aging and age-related diseases, and explores therapeutic strategies targeting this phenomenon, particularly in the context of kidney diseases. By focusing on mesenchymal stem cells and their secretome as potential interventions, it contributes to the understanding of how to mitigate age-related declines in kidney function. However, while the research is solid and relevant, it does not present groundbreaking findings that would significantly advance the field, thus earning a moderate impact score.

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