Oxidant-Based Cytotoxic Agents During Aging

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Abstract
In humans, aging is an inevitable consequence of diminished growth processes after being full-grown. The high order of biological material in cells and tissues is continuously disturbed by numerous physical and chemical destructive impacts. Host-derived oxidant-based cytotoxic agents (reactive species, transition free metal ions, free heme) contribute considerably to this damage. These agents are under control by immediately acting antagonizing principles, which are important to ensure cell and tissue homeostasis. During aging, energy metabolism and supply of tissues with dioxygen and nutrients are increasingly disturbed. In addition, a chronic inflammatory state is developing, a condition known as inflammaging. In this review, the interplay between oxidant-based cytotoxic agents and protective mechanisms is analyzed in dependence on age-based physiological alterations in ATP production. Disturbances in this balance are associated with the development of age-related diseases and comorbidities. The enhanced production of reactive species from dysfunctional mitochondria, alterations in cellular redox homeostasis, and adaptations to hypoxia are highlighted. Examples are given how disturbances between oxidant-based cytotoxic agents and antagonizing principles contribute to the pathogenesis of diseases in persons of advanced age.

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