Role of Oxidative and Nitrosative Stress, Longevity Genes and Poly(ADPribose) Polymerase in Cardiovascular Dysfunction Associated with Aging
Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity. Although aging is inevitable, cardiovascular gerontologists recognize that a better understanding of the aging process in the not-so-distant future will lead to pharmacological interventions that considerably delay the functional decline of the cardiovascular system. Since the original publishing of the free radical theory of aging, an increased production of reactive oxygen species has been implicated both in the aging process and the development of age-related cardiovascular diseases. This review focuses on the role of oxidative and nitrosative stress in cardiovascular dysfunction in aging, downstream mechanisms including activation of NF-kB, and the role of poly(ADP-ribose)polymerase (PARP) and longevity genes that are linked to regulation of cellular redox status and oxidative stress resistance (p66shc, sirtuins, FOXO transcription factors).
Keywords: endothelium, heart, coronary circulation, senescence, inflammation, gene expression, redox status, peroxynitrite
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