SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing

Abstract

Sarcopenia, a skeletal muscle disorder in which loss of muscle mass and function progresses with age, is associated with increased overall frailty, risk of falling and mortality in the elders. Here, we reveal that SESN1 safeguards skeletal muscle from ageing downstream of the longevity gene FOXO3, which we recently reported is a geroprotector in primate skeletal muscle. Knockdown of SESN1 mimicked the human myotube ageing Ying Jing, Yuesheng Zuo, Liang Sun and Zheng-Rong Yu contributed equally to this study.

Exploring In Vivo Models of Musculoskeletal Frailty: A Comprehensive Systematic Review

“…In comparison to frailty found in other organs and systems, such as the brain, the findings available on the musculoskeletal system are scarce. The studies collected are recent, with three performed in 2020 [20,26,27], three in 2021 [21][22][23], two in 2022 [29,30], and a further two in 2023 [24,28]. Only one study was published in 2014 [26].…”

“…In two studies, animal models of frailty were induced through the injection of cardiotoxin (CTX) into the tibialis anterior or quadriceps muscles [28], or of Myelin Oligodendrocyte Glycoprotein (MOG) peptide emulsified in Complete Freud's Adjuvant (CFA) supplemented with heat-inactivated Mycobacterium tuberculosis, subcutaneously [29], in C57BL/6J [29] and C57BL/6 [29] mice.…”

“…Jing et al carried out functional tests in mice of 16 months old, showing that grip strength, physical endurance, and maximal running time and distance were significantly lower in the CTX-injected mice in comparison to sham mice or mice treated with recombinant Sestrin 1 (rSESN1) protein [28].…”

Degeneration Directory: a multi-omics web resource for degenerative diseases

“…Thus, the establishment of a comprehensive database focusing on degenerative diseases and organ degeneration is therefore of the utmost urgency. A comprehensive collection of multi-level omics data encompassing multiple degenerative diseases would facilitate comparisons between aging and degenerative diseases, but more importantly, also support collaborations between research scientists and clinicians to accelerate the development of therapeutic strategies and aging interventions preventing or delaying disease onset ( Liu et al, 2022 ; Jing et al, 2023 ).…”

Sestrin1, 2, and 3 are dispensable for female fertility in mice

“…Ink4/Arf-tg/tg mice are protected against oxidative damage due to an increased expression of antioxidant genes ( Sesn1 and Sesn2 in liver) mediated by p53 [ 24 ]. Sestrin1 (SESN1 ) also protected muscles against aging-induced atrophy [ 25 ]. Sestrin2 (SESN2), a 60 kDa protein [ 26 ] plays a protective role in the context of palmitate-induced lipotoxicity during pregnancy, regulating ER stress, inflammation, and apoptosis, and supports proper trophoblast invasion [ 27 ].…”