Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases

Abstract

Age-associated cardiovascular and neurodegenerative diseases lead to high morbidity and mortality around the world. Sirtuins are vital enzymes for metabolic adaptation and provide protective effects against a wide spectrum of pathologies. Among sirtuins, mitochondrial sirtuin 3 (SIRT3) is an essential player in preserving the habitual metabolic profile. SIRT3 activity declines as a result of aging-induced changes in cellular metabolism, leading to increased susceptibility to endothelial dysfunction, hypertension, heart failure and neurodegenerative diseases. Stimulating SIRT3 activity via lifestyle, pharmacological or genetic interventions could protect against a plethora of pathologies and could improve health and lifespan. Thus, understanding how SIRT3 operates and how its protective effects could be amplified, will aid in treating age-associated diseases and ultimately, in enhancing the quality of life in elders.

Pterostilbene in Combination With Mitochondrial Cofactors Improve Mitochondrial Function in Cellular Models of Mitochondrial Diseases

“…Our results confirm pterostilbene's efficacy potential and demonstrate its ability to activate SIRT3 as well as its mitochondrial deacetylase function. We hypothesize that pterostilbene, through SIRT3 activation, in combination with mitochondrial cofactors could boost antioxidant mechanisms, enhance fatty acids' β-oxidation, regulate mitochondrial protein quality control and adapt the OXPHOS system, as previously reported in the literature (van de Ven et al, 2017;Silaghi et al, 2021). In general, pterostilbene improves mitochondrial homeostasis and thus palliates the negative impact of mitochondrial mutations.…”

Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice

“…Recent study reported that LARP7 can ameliorate cellular senescence and aging through enhancing the activity of SIRT1 ( Yan et al, 2021 ). The increase of the expression or activity of SIRT3 can extend the life span of human ( Silaghi et al, 2021 ; Rose et al, 2003 ). Recently, it was found that reduced SIRT3 abundance in mice can exacerbate age-related periodontal disease ( Chen et al, 2021 ).…”

The roles and mechanisms of epigenetic regulation in pathological myocardial remodeling

“…Like SIRT1, the declined activity of SIRT3 associated with aging is associated with endothelial dysfunction, hypertension, and heart failure (48). Emerging evidence demonstrated that the stimulated SIRT3 activity could ameliorate cell death, fibrosis, and the inflammatory response of cardiomyocytes under the hypertrophic stimulus, thus improving health and lifespan (49)(50)(51). Besides, silencing SIRT3 may sensitize overload-induced heart failure by worsening cardiomyocyte glucose utilization (52), whereas the impaired SIRT3-mediated endothelium cell metabolism could even result in cardiac diastolic dysfunction (53).…”