Swimming exercise activates peroxisome proliferator-activated receptor-alpha and mitigates age-related renal fibrosis in rats.

Aging results in progressive decline of renal function as well as histological alterations including glomerulosclerosis and interstitial fibrosis. The objective of current study was to test the benefits of moderate swimming exercise in aged rats on renal function and structure and investigate its molecular mechanisms. Aged rats of 21-months old were given moderate swimming exercise for 12 weeks. Swimming exercise in aged rats led to reduced plasma levels of creatinine and blood urea nitrogen. Periodic acid-Schiff staining results revealed reduced renal injury scores in aged rats after swimming exercise. Swimming exercise in aged rats mitigated renal fibrosis and downregulated the mRNA expression of Acta2, Fn, Col1a, Col4a, and Tgfb1 in kidneys. Swimming exercise in aged rats attenuated lipid accumulation and reduced levels of triglyceride in kidneys. Swimming exercise in aged rats abated oxidative stress, evidenced by reduced MDA levels and increased MnSOD activities in kidneys. Swimming exercise in aged rats inhibited NF-κB activities and reduced renal expression of pro-inflammatory cytokines including MCP-1, IL-1β and IL-6. Mechanistically, swimming exercise restored mRNA and protein expression of PPAR-α in kidney of aged rats. Furthermore, swimming exercise in aged rats increased expression of PPAR-α-targeting microRNAs including miR-21 and miR-34a. Collectively, swimming exercise activated PPAR-α, which partly explained the benefits of moderate swimming exercise in aging kidneys.