Science advancesSep 9, 2026

Androgen receptor helps muscle stem cells stay active and maintain their supply for life-long repair

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 10, 2026

Abstract

Androgen receptor (AR) expression is essential for maintaining the dormancy of skeletal muscle stem cells (MuSC).

AR is linked to the quiescence of MuSC, acting as a protector of their inactive state.
During muscle repair, AR binding shifts from maintaining dormancy to activating cellular processes.
Removal of AR in young adult mice leads to premature activation of MuSC, affecting their ability to regenerate.
This loss results in a reduced stem cell pool and an unstable environment for muscle repair.
Deficiencies in AR signaling resemble changes seen with aging-related declines in androgen levels.
Supplementing androgens can restore the regenerative capabilities of MuSC.

Simplified

Skeletal muscle stem cells (MuSC) are the guardians of muscle regeneration, sustaining tissue integrity through a delicate balance of quiescence, activation, and lineage commitment. While numerous molecular cues have been implicated in regulating these processes, the influence of androgen receptor (AR) signaling, an essential hormonal pathway for male muscle physiology, has remained largely unexplored. Here, we show that AR expression defines quiescent MuSC and acts as a safeguard of their dormancy. Integrated multiomic analyses reveal a redistribution of AR binding from quiescence-maintenance loci to regulatory elements driving activation and metabolic reprogramming during repair. Loss of AR in young adult mice disrupts this balance, precipitating premature cell-cycle entry, skewed division modalities, depletion of the stem cell reservoir, and destabilization of the niche. These defects converge with hallmarks of aging-associated androgen decline, while androgen supplementation restores regenerative competence. Together, our findings establish AR signaling as a pivotal determinant of MuSC fate and a cornerstone of skeletal muscle homeostasis.

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Androgen receptor helps muscle stem cells stay active and maintain their supply for life-long repair

Abstract

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