Exploration of Drug Science

Table 1

Summary of cellular localization, target proteins, and functions of sirtuins in aging

Sirtuin	Cellular localization	Molecular weight (kDa)	Enzymatic activity	Target proteins	Function	References
Sirt1	Nuclear Cytoplasmic	81.7	Deacetylation Decrotonylation Delactylation	H1, H3, H4, LKB1, AMPK, MnSOD, NF-κB, FOXO, PGC-1α, mTOR	DNA repair, insulin secretion, glucose metabolism, neuroprotection	[7, 54, 55]
Sirt2	Cytoplasmic Nuclear	43.2	Deacetylation Demyristoylation	H4K16, α-tubulin, FOXO, p53	Cell cycle regulation, DNA repair	[22, 56]
Sirt3	Mitochondrial Nuclear Cytoplasmic	43.6	Deacetylation Decrotonylation Delactylation	H3, H4, FOXO, MnSOD, catalase, p53 GDH	ATP production, regulation of mitochondrial metabolism	[26, 27, 54, 55]
Sirt4	Mitochondrial	35.2	ADP-ribosylation Deacylation Deacetylation	AMPK, Glutamate dehydrogenase malonyl-CoA decarboxylase	Insulin secretion, fatty acid oxidation, apoptosis	[30, 57, 58]
Sirt5	Mitochondrial	33.9	Deacetylation Demalonyation Desuccinylation Deglutarylation	SOD, Succinate dehydrogenase	Fatty acid oxidation, oxidative stress	[36, 59–61]
Sirt6	Nuclear	39.1	ADP-ribosylation Demyristoylation Deacetylation Depalmitoylation	H2B, H3, FOXO, PARP1, NF-κB, IGF-1/AKT	DNA repair, genome stability, telomere maintenance, stress response, energy homeostasis	[38, 45, 62, 63]
Sirt7	Nucleolar	44.8	Deacetylation Desuccinylation ADP-ribosylation	H2A, H2B, H3, FOXO3a, RNA polymerase-1, PARP-1, p53, ELK-4	Regulation of rRNA transcription, stress resistance, DNA repair	[64–66]

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AMPK: AMP-activated protein kinase; MnSOD: manganese superoxide dismutase; FOXO: forkhead box protein O; PGC-1α: peroxisome proliferator-activated receptor-γ co-activator-1α; GDH: glutamate dehydrogenase; SOD: superoxide dismutase; IGF-1: insulin-like growth factor-1