TY - JOUR
T1 - A cross-talk between sestrins, chronic inflammation and cellular senescence governs the development of age-associated sarcopenia and obesity
AU - Livshits, Gregory
AU - Kalinkovich, Alexander
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - Inflammation
KW - Obesity
KW - Sarcopenia
KW - Senescence
KW - Sestrins
UR - http://www.scopus.com/inward/record.url?scp=85148955536&partnerID=8YFLogxK
U2 - 10.1016/j.arr.2023.101852
DO - 10.1016/j.arr.2023.101852
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AN - SCOPUS:85148955536
SN - 1568-1637
VL - 86
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 101852
ER -