The interplay between autophagy and mitochondrial dysfunction in oxidative stress-induced cardiac aging and pathology.

Aging is accompanied by a progressive increase in the incidence and prevalence of cardiovascular disease (CVD). Prolonged exposure to cardiovascular risk factors, together with intrinsic age-dependent declines in cardiac functionality, increases the vulnerability of the heart to both endogenous and exogenous stressors, ultimately enhancing the susceptibility to developing CVD in late life. Both increased levels of oxidative damage and the accumulation of dysfunctional mitochondria have been observed in a wide range of cardiac diseases, which may therefore represent a common ground upon which many aspects of CVD develop. In this review, we summarize the current knowledge on the mechanisms whereby oxidative stress arising from mitochondrial dysfunction is involved in the process of cardiac aging and in the pathogenesis of CVD highly prevalent in late life (e.g., heart failure and ischemic heart disease). Special emphasis is placed on recent evidence about the role played by alterations in cellular quality control systems, in particular autophagy/mitophagy and mitochondrial dynamics (fusion and fission), and their interconnections in the context of age-related CVD. Cardioprotective interventions acting through the modulation of mitochondrial autophagy (calorie restriction, calorie restriction mimetics, and the gasotransmitter hydrogen sulfide) are also presented. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy".