The oxidative hypothesis of senescence

Abstract

The oxidative hypothesis of senescence, since its origin in 1956, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. Age-increasing oxidative injuries induced by free radicals, higher susceptibility to oxidative stress in short-lived organisms, genetic manipulations that alter both oxidative resistance and longevity and the anti-ageing effect of caloric restriction and intermittent fasting are a few examples of accepted scientific facts that support the oxidative theory of senescence. Though not completely understood due to the complex "network" of redox regulatory systems, the implication of oxidative stress in the ageing process is now well documented. Moreover, it is compatible with other current ageing theories (e.g., those implicating the mitochondrial damage/mitochondrial-lysosomal axis, stress-induced premature senescence, biological "garbage" accumulation, etc). This review is intended to summarize and critically discuss the redox mechanisms involved during the ageing process: sources of oxidant agents in ageing (mitochondrial -electron transport chain, nitric oxide synthase reaction- and non-mitochondrial- Fenton reaction, microsomal cytochrome P450 enzymes, peroxisomal β -oxidation and respiratory burst of phagocytic cells), antioxidant changes in ageing (enzymatic- superoxide dismutase, glutathione-reductase, glutathion peroxidase, catalase- and non-enzymatic glutathione, ascorbate, urate, bilirubine, melatonin, tocopherols, carotenoids, ubiquinol), alteration of oxidative damage repairing mechanisms and the role of free radicals as signaling molecules in ageing.

Reduced extracellular phagocyte oxidative activity, antioxidant level changes and increased oxidative damage in healthy human blood as a function of age

“…The senescent organism has been considered to be in a state of oxidative stress (Gilca et al 2007;Agarwal and Sohal 1994). Oxidative stress causes increased levels of oxidized proteins, lipids and nucleic acids in cells.…”

Biomedical studies on lipid peroxidation and erythrocyte fragility during the process of aging

“…Aging process is due to increased generation of reactive oxygen species and reactive nitrogen species. Normally there is a balance between tissue oxidant and antioxidant activity [2] . Aging progresses are due to increased generation of free radicals in oxidative stress and one of the victims of free radicals is erythrocytes cell membrane integrity.…”

The Relation Between Thiol/Disulphide Homeostasis and Pseudotumor Cerebri

“…Oxidative substances play an important role both in the pathogenesis of senescence-related degenerative diseases (such as Alzheimer's disease and atherosclerosis), and in conditions resulting from the senescence process such as tissue atrophy. 23,24 This has shown the amount of oxidants increases with aging and the antioxidant systems that try to prevent damage are insufficient in PTC patients.…”