Epigenetic regulation of caloric restriction in aging

Table 2 Selected genes regulated by epigenetic factors during caloric restriction^a

Genes	Gene functions in aging	Epigenetic regulation	CR effects	References
p16 ^INK4a	Tumor suppressor gene that inhibits cell cycle and accumulates during aging	DNA methylation, histone acetylation (mediated by SIRT1 and HDAC1) and histone methylation	Downregulation	[31, 84]
p53	Tumor suppressor gene that induces cell cycle arrest, apoptosis and senescence; increased p53 promotes aging	Histone acetylation (mediated by SIRT1)	Downregulation	[88–90]
H-ras	Oncogene that accelerates aging	DNA methylation	Downregulation	[30]
RUNX3	Transcription factor that plays important roles in development; increases methylation with aging	DNA methylation	Up regulation	[53, 55]
Foxo	Forkhead transcription factors that control various biological functions and involve SIRT1-related longevity	Histone acetylation (mediated by SIRT1)	Downregulation	[91, 92]
Ku70	A component of the NHEJ pathway for DSB repair that regulates apoptosis and DNA repair during aging	Histone acetylation (mediated by SIRT1)	Downregulation	[99, 100]
PGC-1α	Regulates mitochondrial function and glucose homeostasis and interacts with SIRT1 to regulate glucose metabolism during CR	Histone acetylation (mediated by SIRT1)	Upregulation	[34, 83, 93, 94]
hTERT	Tumor promoting gene; increased hTERT expression is correlated with telomerase activation and aging delay	Histone acetylation (mediated by HDAC1) and histone methylation	Upregulation	[31]

^aCR, caloric restriction; hTERT, human telomerase reverse transcriptase; HDAC1, histone deacetylase 1; SIRT1, Sirtuin (silent mating type information regulation 2 homolog) 1; NHEJ, non-homologous end joining; DSB, DNA double-strand break.

ISSN: 1741-7015