Garbage catastrophe theory of aging: imperfect removal of oxidative damage?

Increasing evidence suggests an important role of oxidant-induced damage in the progress of senescent changes, providing support for the free radical theory of aging proposed by Harman in 1956. However, considering that biological organisms continuously renew their structures, it is not clear why oxidative damage should accumulate with age. No strong evidence has been provided in favor of the concept of aging as an accumulation of synthetic errors (e.g. Orgel's 'error-catastrophe' theory and the somatic mutation theory). Rather, we believe that the process of aging may derive from imperfect clearance of oxidatively damaged, relatively indigestible material, the accumulation of which further hinders cellular catabolic and anabolic functions. From this perspective, it might be predicted that: (i) suppression of oxidative damage would enhance longevity; (ii) accumulation of incompletely digested material (e.g. lipofuscin pigment) would interfere with cellular functions and increase probability of death: (iii) rejuvenation during reproduction is mainly provided by dilution of undigested material associated with intensive growth of the developing organism; and (iv) age-related damage starts to accumulate substantially when development is complete, and mainly affects postmitotic cells and extracellular matrix, not proliferating cells. There is abundant support for all these predictions.