Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury

Cells

LjubavaD. Zorova¹  StanislovasS. Jankauskas¹  IrinaB. Pevzner¹  EgorY. Plotnikov¹  DmitryB. Zorov¹  DenisN. Silachev¹  NadezdaV. Andrianova²  VasilyA. Popkov² 

[1] A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia;Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia;

关键词: aging;    dietary restriction;    acute kidney injury;    mitochondria;    autophagy;    mitophagy;    ischemia;    renal tubular cells;   

DOI  :  10.3390/cells7100178

来源: DOAJ

【 摘 要 】

Dietary restriction (DR) is one of the most efficient approaches ameliorating the severity of different pathological conditions including aging. We investigated the protective potential of short-term DR in the model of acute kidney injury (AKI) in young and old rats. In kidney tissue, the levels of autophagy and mitophagy were examined, and proliferative properties of renal cells obtained from rats of different age were compared. DR afforded a significant nephroprotection to ischemic kidneys of young rats. However, in old rats, DR did not provide such beneficial effect. On the assessment of the autophagy marker, the LC3 II/LC3 I ratio, and after staining the tissue with LysoTracker Green, we concluded that in old rats activity of the autophagic-lysosomal system decreased. Mitophagy, as assessed by the levels of PINK-1, was also deteriorated in old animals. Renal cells from old rats showed impaired proliferative capacity, a worse rate of recovery after ischemic injury, increased levels of oxidative stress, accumulation of lipofuscin granules and lower mitochondria membrane potential. The results suggest that the loss of DR benefits in old animals could be due to deterioration in the autophagy/mitophagy flux.

【 授权许可】

Unknown