Biological aging of skeletal muscle in humans

Aging is characterized by changes in body composition and particularly by a gradual loss of skeletal muscle mass, a phenomenon known as Sarcopenia. This age-related decline in muscle mass is accompanied by a loss of strength and a decline of physical performance, named Dynapenia. Both events decrease the autonomy and the quality of life of the individuals affecting about 40-50% of people over the age of 80. Nonetheless, inter-individual differences in prevalence of sarcopenia/dynapenia exist, as some remain fit and strong, whereas other become frail and weak when they get old. Until now, no study has examined the inter-individual variations of muscle tissue and its biomarkers. At the fiber level, age-related variations in skeletal muscle mass induce typological and capillarization modifications. Furthermore, the loss of muscle mass with aging could be associated with serious metabolic consequences or accumulation of intramyocellular lipid droplets. Immunohistochemical studies were performed with muscle biopsies from 30 healthy elderly men, aged 80 ±0.5 years selected from the PROgnostic indicator of cardiovascular and cerebrovascular events (PROOF) cohort, classified into three groups. On the basis of appendicular mass variation between two DEXA at mean interval of seven years, some people lose more muscle mass, named ”Lost”, others remain ”Stable”, and others ”Gain” muscle mass. The loss of skeletal muscle mass was associated with a reduction in Type-I fibers surface area (-24.6%), accompanied by a proportional loss of capillaries number around each fiber-type (CAF) and capillary-to-fiber perimeter exchange index (CFPE) (-15%, -10% respectively), compared to ”Stable” and ”Gain” groups. Also subjects from the ”Lost” group exhibited significant accumulation of intramyocellular lipid droplets in Type-I fibers compared to the ”Gain” (+23%). Lastly, this decline in muscle mass induced a remodeling of the extracellular matrix with an increase in the endomysium area (+12.2% vs Gain). If usually, it is recognized that chronological aging mainly affects Type-II motor units, our results suggest that biological aging is characterized by impairment of Type-I muscle fibers, their microvascular environment and oxidative metabolism for elderly men on their eighties.