The natural process of aging determinates several cardiac modifications with increased susceptibility to heart diseases and ultimately converging on development of chronic heart failure as final stage. These changes mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity, as demonstrated in several humans and animal models of aging. While different theories have been proposed to explain the natural process of aging, it is clear that most of the alterations affect mechanisms involved in cell homeostasis and maintenance. Latest research studies have in particular focused on role of mitochondrial oxidative stress, energy production and mitochondria quality control. This article reviews the central role played by this organelle in aging and the role of new molecular players involved into the progression toward heart failure and potentially susceptible of new "anti-aging" strategies.