‍Abstract
Age-associated impairments in stem cell function correlate with a decline in somatic tissue regeneration capacity during aging. However, the mechanisms underlying the molecular regulation of adult stem cell aging remain elusive. Here, we provide a proteomics landscape of physiologically aged, geriatric muscle stem cells (MuSCs), which illustrated a pre-senescent protein signature. During aging, the mitochondrial proteome and activity are impaired in MuSCs. We identified an RNA-binding protein, CPEB4, which is decreased in various aged tissues and required for MuSC function. CPEB4 regulates the mitochondrial proteomic landscape and activity through mitochondrial translational control. Inhibition of mitochondria function resulted in cellular senescence. MuSCs devoid of CPEB4 induced cellular senescence. Importantly, restoring CPEB4 expression rescued impaired mitochondrial metabolism, improved geriatric MuSC function and prevented cellular senescence in various human cell lines. Our findings provide the basis that CPEB4 regulates mitochondrial metabolism and senescence, with an implication of therapeutic intervention of age-related senescence.

Keywords: aging, senescence, proteomics, Mitochondrial metabolism, Muscle stem cells, Cpeb4

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Zeng W, Zhang W, Tse EHY, Liu J, Dong A, Lam KSW, Luan S, Kung WH, Chan TC, CHeung TH.
Restoration of CPEB4 Prevents Muscle Stem Cell Senescence During Aging.‍

Developmental Cell. 2023;58:1-16.