A cross-talk between sestrins, chronic inflammation and cellular senescence governs the development of age-associated sarcopenia and obesity

Gregory Livshits*, Alexander Kalinkovich

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

The rapid increase in both the lifespan and proportion of older adults is accompanied by the unprecedented rise in age-associated chronic diseases, including sarcopenia and obesity. Aging is also manifested by increased susceptibility to multiple endogenous and exogenous stresses enabling such chronic conditions to develop. Among the main physiological regulators of cellular adaption to various stress stimuli, such as DNA damage, hypoxia, and oxidative stress, are sestrins (Sesns), a family of three evolutionarily conserved proteins, Sesn1, 2, and 3. Age-associated sarcopenia and obesity are characterized by two key processes: (i) accumulation of senescent cells in the skeletal muscle and adipose tissue and (ii) creation of a systemic, chronic, low-grade inflammation (SCLGI). Presumably, failed SCLGI resolution governs the development of these chronic conditions. Noteworthy, Sesns activate senolytics, which are agents that selectively eliminate senescent cells, as well as specialized pro-resolving mediators, which are factors that physiologically provide inflammation resolution. Sesns reveal clear beneficial effects in pre-clinical models of sarcopenia and obesity. Based on these observations, we propose a novel treatment strategy for age-associated sarcopenia and obesity, complementary to the conventional therapeutic modalities: Sesn activation, SCLGI resolution, and senescent cell elimination.

Original languageEnglish
Article number101852
JournalAgeing Research Reviews
Volume86
DOIs
StatePublished - Apr 2023

Funding

FundersFunder number
Ariel University Research & Development Department2000000457
Israel Science Foundation2054/19

    Keywords

    • Inflammation
    • Obesity
    • Sarcopenia
    • Senescence
    • Sestrins

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