Table 1.
Summary of the studies on SIRT1 relevance in intrinsic aging.
| Author | Year | Population | Key Observation |
|---|---|---|---|
| Intrinsic Aging–Basic Information | |||
| Sommer et al. [16] | 2006 | ∆Np63α transgenic mice Normal lung epithelial cells transfected with a vector containing∆Np63α |
transgenic mice exhibited an accelerated aging phenotype in the skin accompanied by a decrease in longevity correlated with levels of SIRT1. In cell culture beta-galactosidase accumulation and typical senescent morphology was rescued by SIRT1. |
| Yang et al. [17] | 2011 | HDFs, Hs68 cell culture exposed to 2-DG and DHEA | 2-DG, but not DHEA, at non-cytotoxic concentrations extends lifespan in parallel with increased intracellular NAD+ levels and SIRT1 activities |
| Kalfalah et al. [18] | 2014 | Skin biopsies of females aged 20–67 | Age-dependent decrease in SIRT1 |
| Kim et al. [19] | 2015 | Passaged HDFs culture | SIRT 1 is down regulated by increasing passage of HDFS. |
| Lee et al. [20] | 2016 | HaCaT keratinocytes | Melatonin-induced autophagy play a protective role through SIRT1 pathway against skin cell damage as a result of hydrogen peroxide-induced cell death. |
| Golubtsova et al. [21] | 2017 | Skin biopsies retrieved from deceased donors: fetuses at pregnant age 20–40 week, people from birth to 85 years old | Age-related decrease in sirtuin 1 content in HDFs is correlated with age-dependent decrease in fibroblasts proliferation. The highest level of SIRT1 is found between 20- to 40-week of pregnancy. |
| Sutter et al. [22] | 2019 | NHEKs and N/TERT-1 | Decreased glucose metabolism increases keratinocytes differentiation by SIRT1 activation. |
| Systemic Sclerosis | |||
| Wei et al. [23] | 2015 | Skin biopsy samples of healthy adults and patients with SSc. Sirt1−/− and wild-type mouse embryonic fibroblasts |
Reduced SIRT1 expression and protein level in SSc skin biopsy samples compared to healthy. Activation of Sirt1 attenuated fibrosis, while inhibition had profibrotic effects. |
| Zerr et al. [24] | 2016 | Skin biopsies of patients with SSc and healthy volunteers Sirt1−/− and wild-type mice |
SIRT1 is decreased in TGF- β-dependent manner in patients with SSc and in experimental fibrosis. SIRT1 activation enhances the profibrotic effects of TGF-β with increased Smad reporter activity, elevated transcription of TGF-β target genes and raised release of collagen. Sirt1 KO inhibited TGF-β/SMAD signaling and reduced release of collagen in fibroblasts. Sirt1−/− mice were less susceptible to fibrosis |
| Zhu et al. [25] | 2017 | Skin biopsy specimens of SSc patients and healthy controls Mice treated with BLM |
SIRT1, activated by RSV, ameliorated cutaneous inflammation and fibrosis in BLM- induced scleroderma. The enhancement of mTOR expression in the skin of the mice was significantly inhibited by Sirt1 activation. |
Abbreviations: SIRT1—sirtuin 1; HDFs—human dermal fibroblasts; 2-DG—2-deoxyglucose; DHEA—dehydroepiandrosterone; NHEKs—Neonatal normal human epithelial keratinocytes; N-TERT1—immortalized keratinocytes; SSc—systemic sclerosis; RSV—resveratrol; BLM—bleomycin; Mtor—mammalian target of rapamycin kinase.