The role of SIRT6 in the regulation of exercise metabolism and the aging process in the skeletal muscle and the central nervous system (CNS).

Life expectancy has significantly increased in the 21st century. However, with longevity, many health concerns became more common, such as neurovegetative diseases, sarcopenia and other metabolic disfunctions. Physical exercise encompasses whole body homeostasis and activates many tissues, organs and physiological systems in addition to benefit in body health, therefore the importance of physical exercise and the need to study its physiological and metabolic effects became relevant in recent years.

In addition to the beneficial effects of physical exercise on healthy life span, sirtuins, an NAD+ dependent deacetylase, plays a major role in genomic stability, gene expression, glucose and fat metabolism, stress response, circadian rhythm and cancer, in addition to increase life span and health span. Hence physical exercise and sirtuins have a common denominator influencing the hallmarks of aging.

In accordance with previous results, forced and voluntary exercise resulted in higher expression of PGC1a, NRF-2 and tFAM and in activation of AMPK. Those factors plays a role in the regulation of mitochondrial biogenesis in the skeletal muscle, in contrast to AKT and p70S6K which control muscle hypotrophy and showed a decreased activation. In addition, forced and voluntary exercise showed an increase in activated AKT in hippocampal brain region that helps in the repression of neuronal cell death. This plays a vital role in slowing the aging process. By finding the interaction between exercise and sirtuins, we will be able to deal with age-related diseases and improve life quality in old age.