Aging and dietary restriction effects on ubiquitination, sumoylation, and the proteasome in the heart.

Dietary restriction (DR), in the absence of malnutrition, is the only intervention known to reliably increase average and maximal lifespan in a variety of organisms including mammals. Because the effects of DR on the heart are poorly understood, in the present study we examined the effects of DR on the ubiquitin-proteasome pathway (UPP) in the heart. In these studies we observed that DR significantly reduced age-related impairments in proteasome-mediated protein degradation, and reduced age-related increases in ubiquitinated, oxidized, and sumoylated protein in the heart. Interestingly, DR did not significantly increase the expression of 20S proteasome subunits or the proteasome maturation factor (POMP-1). These data demonstrate for the first time the effects of aging and DR on proteasome biogenesis and sumoylation in the heart. Cumulatively, our data indicate that DR has many beneficial effects towards the UPP in the heart, and suggests that a preservation of the UPP may be a potential mechanism by which DR mediates beneficial effects on the cardiovascular system.