PGC-1 α in aging and lifelong exercise training-mediated regulation of UPR in mouse liver.

PGC-1α in aging and lifelong exercise training-mediated regulation of UPR in mouse liver. Exp Gerontol. 2017 Aug 08;: Authors: Kristensen CM, Brandt CT, Ringholm S, Pilegaard H Abstract Aging is associated with changes in several metabolic pathways affecting liver function including the adaptive unfolded protein response (UPR). On the other hand, exercise training has been shown to exert beneficial effects on metabolism including the liver and exercise training has been reported to affect hepatic UPR. PGC-1α is a transcriptional coactivator involved in exercise training-induced adaptations in skeletal muscle and liver. Therefore, the aim of the present study was to examine the impact of PGC-1α in aging and lifelong exercise training-induced hepatic UPR in mice. Liver was obtained from young (3months old), aged (15months old) and lifelong exercise trained old wild-type (WT) and whole-body PGC-1α knockout (KO) mice. BiP, IRE1α and cleaved ATF6 protein content increased, whereas PERK protein content was reduced with aging indicating both increased and decreased capacity of specific UPR pathways and increased activity of the ATF6 pathway with aging. Lifelong exercise training prevented the age-associated change in BiP and IRE1α protein, but not cleaved ATF6 protein and resulted in further decreased PERK protein. Taken together, the present study provides evidence that the capacity and activity of the three UPR pathways are differen...
Source: Experimental Gerontology - Category: Geriatrics Authors: Tags: Exp Gerontol Source Type: research