Skeletal muscle-specific calpastatin overexpression mitigates muscle weakness in aging and extends life span

Abstract

This is the first study to investigate the role of calpastatin overexpression on skeletal muscle specific force in aging rodents. Muscle-specific overexpression of calpastatin, the endogenous calpain inhibitor, prevented aging-induced reductions in both EDL and diaphragm specific force and, remarkably, increased life span. These data suggest that diaphragm dysfunction in aging may be a major factor in determining longevity. Targeting the calpain/calpastatin pathway may elucidate novel therapies to combat skeletal muscle weakness in aging.