Abstract
Oxidative stress is both the cause and consequence of impaired functional homeostasis characterizing human aging. The worsening efficiency of stress response with age represents a health risk and leads to the onset and accrual of major age-related diseases. In contrast, centenarians seem to have evolved conservative stress response mechanisms, probably derived from a combination of a diet rich in natural antioxidants, an active lifestyle and a favorable genetic background, particularly rich in genetic variants able to counteract the stress overload at the level of both nuclear and mitochondrial DNA. The integration of these factors could allow centenarians to maintain moderate levels of free radicals that exert beneficial signaling and modulator effects on cellular metabolism. Considering the hot debate on the efficacy of antioxidant supplementation in promoting healthy aging, in this review we gathered the existing information regarding genetic variability and lifestyle factors which potentially modulate the stress response at old age. Evidence reported here suggests that the integration of lifestyle factors (moderate physical activity and healthy nutrition) and genetic background could shift the balance in favor of the antioxidant cellular machinery by activating appropriate defense mechanisms in response to exceeding external and internal stress levels, and thus possibly achieving the prospect of living a longer life.
Highlights
The role of the oxidative stress response in healthy aging and longevity is a hot topic in the field of human aging studies
Species (ROS) are chemically reactive molecules containing oxygen that can be formed by external environmental sources such as radiation, ultraviolet light and pollution or as by-products of endogenous enzymatic activities, as in inflammation and more importantly in oxidative phosphorylation, the biochemical process by which energy released by oxidation of nutrients is converted into ATP by mitochondria
The oxidative stress pathway represents one of the crucial mechanisms linked to human aging and longevity along the evolutionary scale, extending from animal models to humans
Summary
The role of the oxidative stress response in healthy aging and longevity is a hot topic in the field of human aging studies. The stress response is defined as the ability of initiating an array of regulatory processes in response to oxidative stress, including the activation of stress-gene expression and modification of stress-responsive signal transcription pathways. This stress response has been reported to be impaired with aging [6]. It appears that the stress response to stress-induced cellular injury quantitatively increases with advancing age, but is less efficient This failure to effectively respond to cellular challenges has been postulated to contribute to a reduction in stress tolerance and the development or worsening of the most relevant age-related diseases, ranging from degenerative [9,10]. Aware of the difficulty of condensing the vast literature available on this topic in a single review, our aim is to underline the importance of genetic and non genetic factors in the aging organism’s ability to counteract the negative effects of oxidative stress and minimize health risks and possibly increase the individual’s possibilities of achieving a longer life
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