Summary 　Calorie restriction（CR）extends life-span in a wide variety of organisms. It has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species, and that the increased longevity induced by calorie restriction requires the activation of Sir2 by NAD. Moreover, an energy-sensing AMP pathway mediates the lifespan extension induced by a dietary restriction in C. elegans. Importantly, CR, without malnutrition, delays aging and extends life span even in primates by lowering the incidence of aging-related deaths and pathologies such as diabetes, cancer, cardiovascular disease, and brain atrophy. 　We showed that adiponectin induces extracellular Ca influx by AdipoR1, which was necessary for subsequent activation of CaMKKb, AMPK and SIRT1, increased expression and decreased acetylation of PGC-1α, and increased mitochondria in skeletal muscle. Moreover, muscle-specific disruption of AdipoR1 resulted in decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance. Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes. Moreover, agonism of AdipoR1 in muscle could be exercise-mimetics.