Long-term dietary restriction ameliorates ageing-related renal fibrosis in male mice by normalizing mitochondrial functions and autophagy
Backgrounds: During the progression of renal aging, a gradually changes in structures and functions of mitochondria are noticed. Dietary restriction (DR) displays a protective role on aging associated renal decline, however, the exact mechanisms involved is still unclear. The aim of present study is to elucidate whether life-long DR delays renal aging, and explores the potential mechanisms regarding mitochondrial homeostasis. Methods and Results: Eight-week-old C57BL/6 male mice (n=30) were randomly divided into three groups, Young-AL (AL, ad libitum), Aged-AL, and Aged-DR (60% intake of AL). Mice were sacrificed at the age of 7 months (Young) or 20 months (Aged). Heavier weights of body and kidney were accompanied with aging, and DR declined these increases in aged mice. Aging caused extensive tubulointerstitial fibrosis and glomerulosclerosis in kidney. Giant mitochondria with looser and irregular crista were observed in Aged-AL kidney. DR retarded these morphological alterations in aged kidney. In addition, DR reversed the increase of MDA and the decrease of ATP caused by aging. Mitochondrial-related proteins were analyzed to elucidate their involvements. Aging downregulated the renal expressions of VDAC, FOXO1, SOD2, LC3I and II, and upregulated the renal expressions of MFN2 and PINK1. While DR elevated the expressions of VDAC, FOXO1 and LC3I, and reduced the ratio of LC3II to LC3I in aged kidney. Conclusion: Energy deficit, increased oxidative stress and severe fibrosis were noticed in the aged kidney, and DR ameliorated these damages during aging via increasing functional mitochondria, promoting autophagic clearance and reducing oxidative stress.