Cancer and normal ageing

Abstract

Cancer has a monoclonal origin in a pre-mitotic cell and usually a multistep pathogenesis. The initiation of tumor development and most stages in tumor progression involve point mutations, chromosomal rearrangements, and often changes in gene dosage. Simultaneously, there is continuing selection of the cell clones most resistant to growth-regulating substances and/or lacking specific immunologic markers. Normal ageing is partly pre-programmed as demonstrated by the constancy of the maximum survival time for a species under various external conditions resulting in different mean survival times. Emerging evidence of characteristic DNA changes in post-mitotic cells of old individuals may turn out to be part of the programmed changes. However, random accumulation of mutational defects in both pre- and post-mitotic cells is an unavoidable consequence of physics and therefore contributes to normal ageing and the accompanying increase in cell diversity. Cancer incidence increases with age. Firstly, because extended exposure increases the risk of inflicting the DNA changes prerequisite to oncogenesis; secondly, because the progression from one malignant cell to detectable tumor is a matter of 10–30 per cent of a species maximum life span; and thirdly, because some alterations characteristic of normal ageing increase the susceptibility to carcinogens. There probably is an overlap of etiologic/accelerating factors for cancer and ageing. Such aspects of normal ageing such as decline in DNA repair capacity and decline in cellular immune reactivity should facilitate induction and early growth of neoplasia. Age changes that counteract cancer development include (hormonal) loss of proliferative stimulation and depletion of the pool of immature cells at greatest risk.