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.