Sirtuins and their Biological Relevance in Aging and Age-Related Diseases

Zhao Lijun, Cao Jianzhong, Hu Kexin, He Xiaodong, Yun Dou, Tong Tanjun, Han Limin

Table 2 The substrates/targets and functions of sirtuins.

Substrates/targets Function Modification Activation Inhiibition SIRT1 H3K9ac, H3K26ac, H3K16ac, H1K26, H1K9, H3K56, H3K14, H4K16, α-tubulin, p53 Suv39h1, N-Myc, ER, Sirt6, ADAM-10, LKB1, AMPK, NBS1, XPA, MnSOD, WRN, Ku70, FOXO1/3, PGC-1a, PPARα, FXR NF-KB, p300, p66shc, mTOR, HIF-1a, TNF-1a, Histone acctylation, SREBP-1c Glucose metabolism, fatty-acid and cholesterol metabolism, differentiation, insulin secretion, and neuroprotection, stress responses, DNA repair, vascular protection and other cellular processes SIRT2 α-tubulin, H3K56ac, H4K16ac, FOXO, c-Myc, G6PD, PEPCK NF-KB, p53, FoxO1 Cell-cycle control, carbohydrate and lipid metabolism, tubulin and transcription factors deacetylation and anti-inflammatory SIRT3 H3K9, H4K16, H3K56ac, H4K14ac, Ku70, Mn-SOD, FOXO3a, DH2, FAO, GDH, complexI/III, IDH2 p53, HIF-1a, Ros, lipogcncasis regulation of mitochondrial enzymes deacetylation, ATP production, reactive oxygen species (ROS) management, b-oxidation, ketogenesis, cell death, and carbohydrate and lipid metabolism SIRT4 GDH, AMPK, ROS, PDH Insulin secretion, glutamine and fatty acid metabolism and regulate the ATP homeostasis SIRT5 CPS1 SOD1 GLS Urea cycle, regulation of ATP synthesis, metabolism, apoptosis and intracellular signaling, regulation of ammonia detoxification, fatty acid oxidation SIRT6 H2BK12, H3K9ac H3K56ac, WRN FOXO, PARP1, CtIP, P53, DNA-PKcs, CCNDBP1 NF-KB, RELA, TNF-a, IGF-1, HIF-1a, Myc, c-Jun, PGC-1a, GCN5 Telomeres and telomeric functions, DNA repair, metabolic homeostasis, inflammation, stress responses, and genomic stability SIRT7 H2A, H2B, H3 (H3K18) FOXO RNA-POLY-merase, HIF-1a/2a regulates the transcription of rDNA and mediate histone desuccinylation