Table 1.

Summary of the effects of various mammalian sirtuins, their localization, and intracellular targets

Sirtuin and localization	Enzymatic activity	Targets and substrates			Function	Tissue expression	Ageing and age-related diseases
		Modification	Activation	Inhibition			Increase/involvement in CR	Decrease
SIRT1 nuclear/cytosolic	Deacetylase	H1, H3, H4, (H1K26, H1K9, H3K9, H3K56, H3K14, H4K16) α tubulin, p53-(stabilization)	Suv39h1, LKB1, AMPK, NBS1, XPA, Mn-SOD, WRN, Ku70	NFκB, p300, p66shc, mTOR	DNA repair, glucose metabolism, differentiation, neuroprotection, insulin secretion, vascular protection	Brain, adipose tissue, heart, kidney, liver, retina, skeletal muscle, vessels, uterus	Cell survival, longevity, physical activity/increase in CR	Cellular senescence, oxidative stress, inflammation, neurodegeneration, cardiovascular diseases, adiposity, insulin resistance, liver steatosis
			FOXO, PGC-1α
SIRT2 cytosolic/nuclear	Deacetylase	α tubulin, H4K16	FOXO	NFκB, p53	Cell-cycle control (transition from G2 to M phase), adipose tissue development and functionality	Adipose tissue, brain, heart, kidney, liver, skeletal muscle, vessels	Longevity/increase in CR	Oxidative stress, neurodegeneration
SIRT3 mitochondrial/nuclear/cytosolic	Deacetylase	H3, H4 (H3K9, H4K16)	FOXO, Ku70, Mn-SOD, catalase, IDH2	p53, HIF1α	Regulation of mitochondrial metabolism, ATP production	Adipose tissue, brain, heart, kidney, liver, oocytes, skeletal muscle, vessels	Longevity, metabolic health, glucose homeostasis/increase in CR	Oxidative stress, neurodegeneration, cardiac hypertrophy, adiposity, liver steatosis
SIRT4 mitochondrial	ADP-ribosyl-transferase			GDH, AMPK	Insulin secretion, regulation of mitochondrial metabolism, DNA repair	Brain, heart, kidney, liver, vessels, pancreatic β-cells		Fatty acid oxidation
SIRT5 mitochondrial/cytosolic/nuclear	Deacetylase demalonylase desuccinylase		SOD1		Urea cycle	Brain, heart, kidney, liver, vessels, thymus, testis, skeletal muscle	Increase in CR	Oxidative stress, fatty acid oxidation
SIRT6 nuclear (associated with chromatin)	Deacetylase, ADP-ribosyl-transferase	H2B, H3 (H2BK12, H3K9, H3K56), WRN (stabilization)	FOXO, PARP1, CtIP	NFκB, IGF-1	DNA repair, telomere protection, genome stability, cholesterol homeostasis, regulation of glycolysis and gluconeogenesis	Brain, heart, kidney, liver, vessels, retina, skeletal muscle, thymus, testis, ovary	Longevity, glucose homeostasis/increase in CR	Cardiac hypertrophy, adiposity, liver steatosis, inflammation, insulin resistance
SIRT7 nucleolar/nuclear	Deacetylase	H2A, H2B, H3 (H3K18)	FOXO	RNA poly-merase I	Regulation of rRNA transcription, cell cycle regulation, cardioprotection	Heart, vessels, liver, brain, skeletal muscle, peripheral blood cells, spleen, testis	Increase in CR	Cardiac hypertrophy

AMPK AMP-dependent kinase, CtIP C-terminal binding protein interacting protein, DNA-PKcs DNA-dependent protein kinase catalytic subunit, FOXO (FOXO3a, FOXO1) Forkhead box “O” transcription factor, GDH glutamate dehydrogenase, H1, H2A, H2B, H3, H4 histone; HIF1α hypoxia-inducible factor 1α, IGF-1 insulin-like growth factor 1, IDH2 isocitrate dehydrogenase 2, LKB1 liver kinase B1, Mn-SOD manganese superoxide dismutase, mTOR mammalian target of rapamycin, NBS1 Nijmegen breakage syndrome 1, NFκB nuclear factor κB, PARP1 poly(ADP-ribose) polymerase 1, PGC-1α PPARγ coactivator1α, SOD1 superoxide dismutase 1, Suv39H1 suppressor of variegation 3–9 homolog 1, WRN Werner syndrome ATP-dependent helicase, XPA xeroderma pigmentosum group A