Overall

• [ ] Increased expression levels of Sirtuin, especially yeast SIR2 and its homologues, extends the lifespan of budding yeast S. cereviseasae, worms C. elegans, fruit flies D. melanogaster, and mice
• [x] Sirtuins are found to especially interact with all the major conserved longevity pathways, such as AMP-activated protein kinase (AMPK), insulin/IGF-1 signaling (IIS), target of rapamycin (TOR), and forkhead box O (FOXO). Of these, FOXO transcription factor is the most fascinating target of Sirtuin
• [ ] SIRT3, SIRT4, and SIRT5 are mitochondrial proteins. SIRT6 is a nuclear protein and SIRT7 is nucleolar (Liszt et al., 2005; Ford et al., 2006; Figure ​Figure1).1)
• [x] Sirtuins (SIRT1-7) can be divided into nuclear (SIRT1, SIRT6, and SIRT7), mitochondrial (SIRT3, SIRT4, and SIRT5) and cytosolic (SIRT2) forms, and some sirtuins are found in more than one compartment
• [x] Sirtuins (SIRT1–7) are NAD +-dependent deacylases that promote homeostasis
• [x] promote longevity in diverse species
• [ ] sirtuin activating compounds (STACs)
• [ ] Sirtuins are believed to be the major reason why calorie restriction (CR) and exercise improve health (Bordone et al., 2007; Guarente, 2005; Rogina and Helfand, 2004)

Sirt1

• [ ] We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population
• [x] Acts as a transcription factor and a cofactor in addition to being a target for histone and non-histone proteins
• [x] SIRT1 protects cells against oxidative stress, regulates glucose/lipid metabolism, and promotes DNA stability by binding to and deacetylating several substrates. Because of these protective roles against several age-related pathologies, SIRT1 is thought as one of the candidate molecules for promoting healthy aging.
• [x] Also, a previous study performed with SIRT1 knockout mice showed a significantly shorter lifespan compared with wild-type mice
• [ ] Alcendor et al. [9, 10] reported that the protective effects of SIRT1 are because of its inhibitory effect on p53 acetylation which stimulates cell death mechanisms and its stimulatory effect on cytoprotective- and stress resistance-genes activator FoxO1a which prevents oxidative stress by upregulating catalase activity.
• [ ] Nowadays, the epigenetic modification of genes also becomes a hot subject for gene-environment interactions to provide essential life styles by decreasing the risk of age-related diseases
• [ ] A study made in 2015 shows that Sirt1 levels are significantly higher in old adults than in young children
• [ ] Therefore, increased SIRT1 expression and activity may be effective for keeping the cells and organs functioning properly for longer times
• [ ] SIRT1 level between children and adults (from age 3 to 55) may suggest that SIRT1 levels are controlled during a long period of times in our lives and its expression dramatically increases in older ages
• [ ] SIRT1 activation shows promise for the treatment of aging and age-related diseases