DELETERIOUS NETWORK HYPOTHESIS OF AGING

It is becoming increasingly apparent that free-radical damage, mitocho ndrial 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-promoti ng factors, a unifying hypothesis of senescence - the deleterious netw ork hypothesis of aging - is proposed: In living organisms, both endog enous and exogenous detrimental factors produce age-dependent accumula tion of triggering of a deleterious network, which is constructed on t he basis of the interactions among oxidative impairments, mitochondria l defects, calcium mismetabolism and glycation/Maillard reaction. The age-related triggering of the network leads to numerous senescent alte rations. It appears that this novel theory has synthesized multiple hy potheses 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 approa ches which can inhibit the initiation of the four key age-promoting fa ctors should be applied combinatively to slow down the aging process a nd to prevent and treat age-associated illnesses.