Short-term calorie restriction protects against renal senescence of aged rats by increasing autophagic activity and reducing oxidative damage

Abstract

To explore the effect of short-term calorie restriction (CR) on renal aging, 8-week CR with 60% of the food intake of the ad libitum group was administered in 25-month-old male Sprague-Dawley rats. Aged rats subjected to short-term CR had lower body weight, level of triglycerides and ratio of urine protein to urine creatinine, respectively. Short-term CR blunted the increased glomerular volume, the degree of fibrosis, p16 and the positive rate of senescence-associated β-galactosidase staining of the kidneys in old ad libitum group. Light chain 3/Atg8 as an autophagy marker exhibited a marked decline in aged kidneys, which was increased by short-term CR. The levels of p62/SQSTM1 and polyubiquitin aggregates, which were increased in older kidneys, were blunted by short-term CR. Short-term CR retarded the level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage. Moreover, we found an increased level of SIRT1 and AMPK, and a decreased level of mTOR in aged kidneys after short-term CR. These results suggested that short-term CR could be considered as a potential intervention for retardation of renal senescence by increasing autophagy and subsequently reducing oxidative damage. Three master regulators of energy metabolism, SIRT1, AMPK and mTOR are associated with these effects.

Keywords: 8-OHdG; 8-hydroxydeoxyguanosine; AL; AMP-activated protein kinase; AMPK; Aging; Autophagy; CKD; CR; Calorie restriction; Kidney; O; Oxidative damage; PAS; SA-β-gal; SDRs; Sprague–Dawley rats; Y; ad libitum; calorie restriction; chronic kidney disease; mitochondrial DNA; mtDNA; old; periodic acid-Schiff; senescence-associated β-galactosidase; young.