Proposed tandem effect of physical activity and sirtuin 1 and 3 activation in regulating glucose homeostasis

Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD⁺)-dependent protein deacetylases enzymes (SIRT1-7) that play an important role in maintaining cellular homeostasis. Among those, the most studied are SIRT1 and SIRT3, a nuclear SIRT and a mitochondrial SIRT, respectively, which significantly impact with an increase in mammals’ lifespan by modulating metabolic cellular processes. Particularly, when activated, both SIRT1 and 3 enhance pancreatic β-cells’ insulin release and reduce inflammation and oxidative stress pancreatic damage, maintaining then glucose homeostasis. Therefore, SIRT1 and 3 activators have been proposed to prevent and counteract metabolic age-related diseases, such as type 2 diabetes mellitus (T2DM). Physical activity (PA) has a well-established beneficial effect on phenotypes of aging like β-cell dysfunction and diabetes mellitus. Recent experimental and clinical evidence reports that PA increases the expression levels of both SIRT1 and 3, suggesting that PAmay exert its healthy contribute even by activating SIRTs. Therefore, in the present article, we discuss the role of SIRT1, SIRT3, and PA on β-cell function and on diabetes. We also discuss the possible interaction between PA and activation of SIRTs as a possible therapeutic strategy to maintain glucose hemostasis and to prevent T2DM and its complications, especially in the elderly population.