Sirtuins triggered by fasting - potential mediators of longevity

Abstract

Introduction: Studies reveal that caloric restriction (CR) and fasting slow down aging, improve over­all wellbeing and prolong lifespan. Sirtuins (SIRTs) are a family of oxidized nicotinamide adenine dinucleotide (NAD+) - dependent protein deacetylases established to be key molecules that mediate the life-prolonging effects of CR. This study aims to represent a brief summary about the relation be­tween CR and SIRTs activity. Materials and methods: A literature search of relevant publications in PubMed database was conduct­ed, the key words used were aging, CR and aging, fasting, sirtuins, longevity, anti-aging effects of fasting, sirtuins and CR, SIRTs and aging. Articles describing the relation between sirtuins, CR and aging were selected. Results of the research were obtained by comparing a significant amount of ar­ticles regarding studies about the benefits of CR on cell cultures, yeast, mice and human subjects and changes in SIRTs activity in response. Results: In yeast an extra copy of the Silent Information Regulator 2 gene (Sir2) increases lifespan, while deletion of this gene shortens it. In addition, glucose restriction (GR) increases replicative lifes­pan in wild-type, whereas GR in Sir2-deleted model it fails to extend lifespan. Mice undergoing CR have increased lifespan and SIRT expression, while SIRT-deficient mice are irresponsive to CR. More­over, they have metabolic dysfunctions causing diseases and premature death compared to wild-type. SIRT6 play an important role in maintaining telomeric chromatin integrity. In primary human fi­broblasts, removal of SIRT6 causes telomere damage leading to sequence loss. Ultimately, telomere dysfunction triggers premature cellular senescence. Intermittent fasting (IF) has the potential to pro­duce effects similar to CR. It is observed that human subjects undergoing IF have increased SIRT3 ex­pression. Conclusion: Sirtuins are considered as potential target for preventing and treating many aging-relat­ed diseases. The relation between CR and SIRTs activation confirms the possibility of implementing regulated fasting as an approach to improve health and to extend lifespan.