Targeted Bmal1 restoration in muscle prolongs lifespan with systemic health effects in aging model.

ABSTRACT: Disruption of the circadian clock in skeletal muscle worsens local and systemic health, leading to decreased muscle strength, metabolic dysfunction, and aging-like phenotypes. Whole-body knockout mice that lack Bmal1, a key component of the molecular clock, display premature aging. Here, by using adeno-associated viruses, we rescued Bmal1 expression specifically in the skeletal muscle fibers of Bmal1-KO mice and found that this engaged the circadian clock and clock output gene expression, contributing to extended lifespan. Time course phenotypic analyses found that muscle strength, mobility, and glucose tolerance were improved with no effects on muscle mass or fiber size or type. A multiomics approach at 2 ages further determined that restored muscle Bmal1 improved glucose handling pathway

SUBMITTER: Gutierrez-Monreal MA 

PROVIDER: S-EPMC11601919 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature