Carcinogenesis and aging 20 years after: escaping horizon.

Carcinogenesis is a multistage process: neoplastic transformation implies the engagement of a cell through sequential stages, and different agents may affect the transition between continuous stages. Multistage carcinogenesis is accompanied by disturbances in tissue homeostasis and perturbations in nervous, hormonal, and metabolic factors which may affect antitumor resistance. The development of these changes depends on the susceptibility of various systems to a carcinogen and on the dose of the carcinogen. Changes in the microenvironment may condition key carcinogenic events and determine the duration of each carcinogenic stage, and sometimes they may even reverse the process of carcinogenesis. These microenvironmental changes influence the proliferation rate of transformed cells, the total duration of carcinogenesis and, consequently, the latent period of tumor development. 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 two mechanisms: tissue accumulation of cells in late stages of carcinogenesis and alterations in internal homeostasis, in particular, alterations in immune and endocrine system. Aging is associated with number of events at molecular, cellular and physiological levels that influence carcinogenesis and subsequent cancer growth.