Oxidant-Based Cytotoxic Agents During Aging: From Disturbed Energy Metabolism to Chronic Inflammation and Disease Progression

In humans, aging is an inevitable consequence of diminished growth processes after reaching maturity. The high order of biomolecules 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, and free heme) contribute considerably to this damage. These agents are under the control of immediately acting antagonizing principles, which are important to ensure cell and tissue homeostasis. In this review, I apply the concept of host-derived cytotoxic agents and their interplay with antagonizing principles to the aging process. During aging, energy metabolism and the supply of tissues with dioxygen and nutrients are increasingly disturbed. In addition, a chronic inflammatory state develops, a condition known as inflammaging. The balance between oxidant-based cytotoxic agents and protective mechanisms is analyzed depending on age-based physiological alterations in ATP production. Disturbances in this balance are associated with the development of age-related diseases and comorbidities. An enhanced production of reactive species from dysfunctional mitochondria, alterations in cellular redox homeostasis, and adaptations to hypoxia are highlighted. Examples of how disturbances between oxidant-based cytotoxic agents and antagonizing principles contribute to the pathogenesis of diseases in persons of advanced age are given.