Table 2.

Summary of the studies on SIRT1 relevance in progeroid syndromes.

Author	Year	Mutation	Population	Key Observations
Kayho et al. [26]	2008	WRN	Sirt1-heterozygous mice, homozygous mutant offspring Sirt1−/− HEK293T cells	CR of rats led to a simultaneous increase in the level of WRN and SIRT1 protein. WRN was decreased in Sirt1-deficient mice and HEK293T cells, treated with sirtuin inhibitors.
Fan et al. [27]	2010	XPA	HeLa, H1299, HEK293T cells and XPA-deficient fibroblasts	UVR augments the XPA and SIRT1 interaction, which leads to cell survival. Phosphorylation works in acute response to UV-induced damage, while acetylation is involved in DNA repair complex Downregulation of SIRT1 delays the removal of CPD, but no 6-4PPs lesion. SIRT1 functions as a tumor suppressor.
Fang et al. [28]	2014	XPA	In silico on-line database www.mitodb.com, accessed on 6 April 2021 (Scheibye-Knudsen et al., 2013)	In XPA, CS, and AT, SIRT1 attenuation leads to decreased mitophagy through the depression of PGC-1α and UCP2. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD+-SIRT1-PGC-1α axis triggered by hyperactivation of the DNA damage sensor PARP1.
Jarrett et al. [29]	2018	XPA	A375 melanoma cells UV-irradiated	SIRT1-dependent deacetylation of XPA augments cAMP-enhanced NER.
Ming et al. [30]	2010	XPC	Human skin tumor samples UV irradiated	Inhibition of SIRT1 impairs global genome NER through suppressing the transcription of XPC in a SIRT1 dependent manner. SIRT1 levels are significantly reduced inhuman skin tumors from Caucasian patients. SIRT1 acts as a tumor suppressor.
Velez-Cruz et al. [31]	2013	XPD subunit of TFIIH	Human primary fibroblast	Transcriptional arrest upon UVR in XP-D/CS cells results from gene repression mediated by SIRT1 and may be restored with a Sirt1-specific inhibitor or downregulation by siRNA.
Scheibye-Knudsen et al. [32]	2014	CSB	Four-month-old mice SV40-transformed CS1AN cells Bristol N2 (WT) and csb-1 worms	Premature aging results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. B-hydroxybutyrate levels are increased by the high-fat diet, and b-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes.
Fang et al. [33]	2016	ATM	Primary neurons, nematodes, Atm−/− mice	A-T laboratory animal models exhibit NAD+ depletion and impaired SIRT1 activity. NAD+ replenishment improves lifespan and healthspan in worms and mice and ameliorates A-T phenotypes through upregulation of mitophagy and DNA repair.
Liu et al. [34]	2012	LMNA	HEK293 cells, mouse embryonic fibroblasts, HDFs derived from HGPS patients and healthy individuals, cells harboring LMNA mutations, Zmpste24/mice, bone marrow stromal cell and hematopoietic stem	Lamin A activates SIRT1 deacetylase. Resveratrol enhances SIRT1 activity by increasing its interaction with lamin A. Prelamin A or progerin has significantly reduced association with SIRT1 in cells. SIRT1 deacetylase activity is compromised in progeroid cells. Resveratrol alleviates progeroid features and extends life span in progeria mice.

Abbreviations: WRN—Werner syndrome ATP-dependent helicase; XPA—xeroderma pigmentosum A gene/protein; XPC—xeroderma pigmentosum C gene/protein; XPD—xeroderma pigmentosum D gene/protein; TFIIH—transcription factor IIH; CSB—Cockayne syndrome B gene/protein; ATM—ataxia telangiectasia mutated kinase serine/threonine; LMNA—lamin A/C gene; CR- caloric restriction; UVR—ultraviolet radiation; CPD—cyclobutane pyrimidine dimers; 6-4PPs—pyrimidine 6-4 pyrimidone photoproducts; PGC1α—Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha; PARP1—Poly[ADP-ribose] polymerase 1; UCP2—mitochondrial uncoupling protein 2; NER—nucleotide excision repair complex; A-T—ataxia telangiectasia; SIRT1—sirtuin 1; HDFs—human dermal fibroblasts; HGPS—Hutchinson Gilford progeria syndrome.