Chronic diseases are the leading drivers of the nation’s $3.8 trillion in annual health care costs. International laboratories are increasingly focused on fitness and preventive strategies because prolonging healthy survival is not only desirable, but also represents a moral goal of any modern and responsible society. In fact, in addition to preventing human suffering, extension of healthy lifespan could save over $7 trillion in the United States alone. Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD+) dependent protein deacetylases enzymes that play an important role in maintaining cellular homeostasis. Among those, the most studied are nuclear SIRT (SIRT1) and mitochondrial SIRT (SIRT3), which significantly impact humans’ lifespan by modulating metabolic cellular processes. These proteins begin to decrease after 35 years of age, and after 60 years of age they are minimally produced by the human body. The progressive decrease of SIRTs leads to a series of overall inefficiencies in the human body, contributing to the loss of personal autonomy, with deterioration and shortening of healthy lifespan and overall longevity. SIRTs can be activated by caloric restriction, resulting in a doubling of lifespan in preclinical model systems; however, they can also be activated by exercise and plant-derived natural compounds.

Exercise is certainly still beneficial in older individuals to maintain fitness and overall wellness but may become insufficient for SIRTs activation. Nevertheless, older individuals could still benefit from selected protective factors needed to restore SIRTs and their capacity to correct altered methylation patterns, to improve the function and prevent dedifferentiation of specialized tissues like the Central Nervous System. Those SIRTs activating substances are contained in common foods but can be taken also in the form of supplements that could help decrease the extra calories associated with the intake of an effective amount of fruit and vegetables containing natural SIRTs activators. This review outlines the potential synergistic and complementary role of exercise and supplementation with selected protective substances in SIRTs activation and wellness, to prevent or delay progression of age-related chronic diseases.

Sirtuins, SIRT, Exercise, Sirtuin Activators, Polyphenols, Healthspan, Aging