Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging
Protein & Cell
;
(12): 497-512, 2023.
Artigo
em Inglês
| WPRIM
| ID: wpr-982529
ABSTRACT
Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Primatas
/
Envelhecimento
/
Músculo Esquelético
/
Sarcopenia
/
Proteína Forkhead Box O3
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2023
Tipo de documento:
Artigo
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