The relationship between aging and carcinogenesis: a critical appraisal.

The incidence of cancer increases with age in humans and in laboratory animals alike. There are different patterns of age-related distribution of tumors in different organs and tissues. Aging may increase or decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer by several mechanisms: (1) tissue accumulation of cells in late stages of carcinogenesis; (2) alterations in homeostasis, in particular, alterations in immune and endocrine system and (3) telomere instability linking aging and increased cancer risk. Increased susceptibility to the effects of tumor promoters is found both in aged animals and aged humans, as predicted by the multistage model of carcinogenesis. Available evidence supporting the relevance of replicative senescence of human cells and telomere biology to human cancer seems quite strong, however, the evidence linking cellular senescence to human aging is controversial and required additional studies. Data on the acceleration of aging by carcinogenic agents as well as on increased cancer risk in patients with premature aging are critically discussed. In genetically modified mouse models (transgenic, knockout or mutant) characterized by the aging delay, the incidence of tumors usually similar to those in controls, whereas the latent period of tumor development is increased. Practically all models of accelerated of aging in genetically modified animals show the increase in the incidence and the reduction in the latency of tumors. Strategies for cancer prevention must include not only measures to minimize exposure to exogenous carcinogenic agents, but also measures to normalize the age-related alterations in internal milieu. Life-span prolonging drugs (geroprotectors) may either postpone population aging and increase of tumor latency or decrease the mortality in long-living individuals in populations and inhibit carcinogenesis. At least some geroprotectors may increase the survival of a short-living individuals in populations but increase the incidence of malignancy.