Oxidative stress in aging: Theoretical outcomes and clinical evidences in humans

Oxidative damage accumulation in macromolecules has been considered as causative of cellular damage and pathology. Considering early observations of Gershman that oxygen free radicals exist in vivo in the 1950s Denham Harman proposed seminal that reactive oxygen species are a cause of aging (free radical theory of aging). The goal of this review is to analyze recent findings related Harman's theory. In this regard, we have focused primarily on theoretical analyses of oxidative stress and their biological impact. It is not the only theorem proposed to explain the mechanism(s) involved in aging at the molecular level. We also discuss how this theory is related to other areas of research specifically, the mitochondrial hypothesis of aging, molecular and cell basis to chronic inflammation and disease appearance, caloric restriction experiments and the most recent clinical studies in healthy human's populations. We reviewed evidences of alterations in biological events likely account for the age-related decline in the ability of cells to respond oxidant stimuli, which compromises homeostasis, increases vulnerability to OS and contribute to senescence. Clearly further studies will be needed to contribute to strategies elucidation such could offer significant benefits for the aged humans.