Deleterious network hypothesis of aging.

It is becoming increasingly apparent that free-radical damage, mitochondrial defects, glycation/Maillard reaction and calcium dyshomeostasis play crucial roles in cellular and organism senescence. Based on the evidence indicating close relationships among these four aging-promoting factors, a unifying hypothesis of senescence-the deleterious network hypothesis of aging-is proposed: In living organisms, both endogenous and exogenous detrimental factors produce age-dependent accumulation of triggering of a deleterious network, which is constructed on the basis of the interactions among oxidative impairments, mitochondrial defects, calcium mismetabolism and glycation/Maillard reaction. The age-related triggering of the network leads to numerous senescent alterations. It appears that this novel theory has synthesized multiple hypotheses of aging, and is capable of providing consistent explanations to a larger number of senescent changes than any previous hypotheses. Based on the new theory of senescence, it is proposed that the approaches which can inhibit the initiation of the four key age-promoting factors should be applied combinatively to slow down the aging process and to prevent and treat age-associated illnesses.