Table 2.

Histone modifications in age-related kidney diseases.

Allele	Sample	Dysregulation	Target	Brief Role	Reference
HDAC3	HDAC3 knockout mice	Upregulated	Klotho	Aberrant HDAC3 induction contributes to renal fibrogenesis through inhibiting Klotho, a renal epithelium-enriched aging suppressor.	[26]
Sirt1	Mice (5, and 26–28 months)	Downregulated	PGC1α, FOXO3/4, NF-κB	Podocyte-specific Sirt1 knockdown accelerates kidney injury in aging mice through Sirt1-mediated deacetylation of downstream targets.	[121]
Sirt1	Mice (3 and 24 months)	Downregulated	FOXO3	Long-term calorie restriction-induced upregulation of Sirt1 in aged kidney attenuated hypoxia-associated mitochondrial and renal damage by enhancing Bnip3-dependent autophagy.	[122]
Sirt1	Mice (24 months)	Downregulated	AMPK and PPARα signaling	Pharmacological activation of Sirt1 by resveratrol attenuates age-related renal injury through activation of AMPK and PPARα signaling.	[123]
Sirt1	Mice (5 weeks and 24 months)	Downregulated	HIF-1α	Sirt1-induced deacetylation of HIF-1α may have protective effects against tubulointerstitial damage in aged kidney.	[124]
Sirt1	Mice (12 weeks and 15 months)	Not mentioned	MMP-14	Endothelial Sirt1 deficiency contributes to nephrosclerosis through downregulation of MMP-14, which is primarily associated with vascular aging and fibrosis.	[125]
Sirt1	Mice (3–4, 11–12, and 22–25 months)	Down-regulated	Not mentioned	Angiotensin II type 1 receptor-associated protein (ATRAP) plays an important role in inhibiting kidney aging, possibly through sirt1-mediated inhibition of oxidative stress.	[127]
Sirt3	Mice (15 months WT and Sirt3-KO)	Downregulated	Glycogen synthase kinase-3 beta (GSK3β)	Sirt3 blocks aging-associated renal fibrosis through deacetylating and activating GSK3β.	[128]
Sirt6	Mice (6 and 24 months)	Downregulated	NF-kB signaling	CR-induced Sirt6 activation delays age-dependent renal degeneration through suppressing the NF-kB signaling pathway.	[129]
Sirt6	Mice (1, 2, 7 months WT and Sirt6-KO)	Downregulated	Unknown	Sirt6 deficiency results in progression of glomerular injury in the aged mice kidney	[130]