An unprecedented increase in human life expectancy has taken place over the past centuries, thus raising the number of elderly people globally. Despite advances in medicine, cardiovascular disease remains the major cause of mortality and morbidity among elderly people and poses a great burden to health care services. As aging is inevitable and represents a risk factor for cardiovascular disease, a better understanding of its underlying mechanism will be crucial to design tailored therapeutic options. Indeed, the dysregulation of aging and longevity genes has been implicated in lifespan by regulating numerous cellular processes, which alter both structural and functional aspects of the cardiovascular system. In this review, several lifespan-determining genes are reviewed, in particular, for their involvement in regulating cardiovascular health via inflammation and oxidative stress. Lastly, several promising prevention and treatment approaches such as an anti-aging and age-associated cardiovascular disease intervention are also described.