Table 3.
Summary of the studies on SIRT1 relevance in extrinsic aging.
| Author | Year | Population | Key Observation |
|---|---|---|---|
| Extrinsic Aging | |||
| Ohguchi et al. [35] | 2010 | HDFs treated with SIRT1 inhibitor, activator and IL-1β | SIRT1 negatively regulates transcription of MMP-1 and MMP-3 and controls both basal and IL-1β-induced MMP expression |
| Taniguchi et al. [36] | 2012 | HDFs exposed to H2O2, AA, AA-2G | H2O2 reduced SIRT1 in HDFs. Pretreatment with AA-2G significantly inhibits reduction, whereas AA had no effect. |
| Lim et al. [37] | 2020 | HaCaT, HDFs and B16F10 cells exposed to UVB irradiation |
AL has an antiwrinkle activity in damaged skin and can inhibit melanogenesis, regulates baseline MMP expression and induces collagen production in HDFs. AL inhibits elastase and MMP-1 and induces type 1 procollagen. AL increased the expression of SIRT1 |
| Extrinsic Aging–UV Irradiation | |||
| Cao et al. [38] | 2009 | HaCaT, p53 wild-type mouse, MEFs and p53 knockout MEFs | UVR and H2O2 downregulate SIRT1. RSV protects against cell death, whereas SIRT inhibitors enhance it |
| Zhang et al. [39] | 2015 | HDFs exposed to UVA irradiation | PQQ reduces the expression of senescence markers MMP1, MMP3 and beta-galactosidase by up-regulation of SIRT1 |
| Chung et al. [40] | 2015 | HS27 culture cell and HR1 hairless mouse exposed to UVB irradiation | SIRT1 overexpression protects fibroblasts from UVB-induced cell cycle arrest by p53 deacetylation. SIRT1 thorough FOXO3α increases resistance to the oxidative stress. |
| Calapre et al. [41] | 2017 | ex vivo skin models, taken from non-sun exposed skin of healthy donors and NHEKs exposed to UVB plus heat | SIRT1 mediates UVB plus heat induced survival of DNA damaged keratinocytes by: decrease in p-53 acetylation and downregulation of its downstream pathways, including: BAX, ERCC1, XPC Increase in Ki67. |
| Lei et al. [42] | 2018 | Primary HDFs obtained from foreskins of healthy human donors aged 5–20 years exposed to UVA irradiation | Fluorofenidon alleviates HDFs senescence by inhibiting the mTOR and increasing SIRT1 |
| Ding et al. [43] | 2018 | Epidermis isolated from skin biopsies obtained from the outer forearm and the buttock of healthy females | Lower expression of HDAC1 and SIRT1 in sun-exposed skin compared with matched non-exposed skin |
| Li et al. [44] | 2020 | HaCaT exposed to UVA irradiation | α-l-Hexaguluroic acid hexasodium salt (G6) increases mitochondrial metabolism, alleviates oxidative stress, reverses the downregulation of SIRT1 and pGC-1a expression levels |
| UV-Related Carcinogenesis | |||
| Hida et al. [45] | 2007 | Immunohistochemical staining for SIRT1 expression in 87 cases of skin tumors and 20 normal skin samples. | Sun-exposed and sun-protected skin regions did not differ in SIRT1 expression. SIRT1 was overexpressed in all samples of AK, BD, SCC and BCC. SIRT1 overexpression may have some relevance to the early stage of skin carcinogenesis. |
| Ming et al. [46] | 2015 | Sirt1 cKO and cHet, WT mice, and NHEKs exposed to UVB irradiation. Human skin samples of SCC. | Sirt1 cHET promotes UVB-induced skin tumorigenesis, whereas cKO Sirt1 suppresses skin tumor development but sensitizes the mice to chronic solar injury. In mouse skin, Sirt1 is haploinsufficient for UVB-induced DNA damage repair. SIRT1 is downregulated in parallel with XPC in human SCC. cKO deletion of Sirt1 augments p53 acetylation and sensitizes the epidermis to UVB-induced apoptosis in vivo, while heterozygous has no such effect. UVB induced tumor formation in Sirt1 WT and Sirt1 cHet mice but not in Sirt1 cKO mice. |
| Brandl et al. [47] | 2019 | human BCC human and murine normal skin |
The c-MYC-NAMPT-DBC1-SIRT1 positive feedback loop may play a role in the development of BCCs. |
Abbreviations: SIRT1—sirtuin1; HDFs—human dermal fibroblasts; IL-1β—interleukin 1β; MMP1- matrix metalloproteinase 1, MMP3—matrix metalloproteinase 3; AA—ascorbic acid; AA-2G—2-O-α-glucopyranosyl-l-ascorbic acid; UVR—ultraviolet radiation; UVB—ultraviolet B; UVA—ultraviolet A; AL—Lactobacillus acidophilus KCCM12625P; MEFs—mouse embryonic fibroblasts; RSV—resveratrol; H2O2—hydrogen peroxide; PQQ—pyrroloquinoline quinone; NHEKs—neonatal normal human epithelial keratinocytes; BAX—BCL2 Associated X, Apoptosis Regulator; ERCC1—Excision Repair 1, Endonuclease Non-Catalytic Subunit; XPC—xeroderma pigmentosum C protein; FOXO3α—Forkhead Box O3; mTOR—mammalian target of rapamycin kinase; HDAC1—histone deacetylase 1; pGC-1a—peroxisome proliferator-activated receptor gamma coactivator 1-alpha; AK—actinic keratosis; BD—Bowen’s disease; SCC—squamous skin carcinoma; BCC—basal cell carcinoma; cKO—homozygous knockout; cHet—heterozygous deletion; WT—wild type; DBC1—Deleted in Breast Cancer 1; NAMPT—Nicotinamide phosphoribosyltransferase.