Aging and Cancer: The Waning of Community Bonds

Abstract

Cancer often arises in the context of an altered tissue landscape. We argue that a major contribution of aging towards increasing the risk of neoplastic disease is conveyed through effects on the microenvironment. It is now firmly established that aged tissues are prone to develop clones of altered cells, most of which are compatible with a normal histological appearance. Such increased clonogenic potential results in part from a generalized decrease in proliferative fitness, favoring the emergence of more competitive variant clones. However, specific cellular genotypes can emerge with reduced cooperative and integrative capacity, leading to disruption of tissue architecture and paving the way towards progression to overt neoplastic phenotypes.

Keywords: aging; cancer; clonal growth; microenvironment; tissue ecology.

Figure 1

Protective mechanisms against cancer. The survival and proliferation of altered cells can be prevented by three main mechanisms. Cell competition (left panel) is a tissue intrinsic mechanism, where unfit cells can be actively eliminated by fitter surrounding cells; cell senescence (central panel) is a cell intrinsic mechanism, where altered cells enter a permanent state of mitotic block; immune surveillance (right panel) represents an important tissue extrinsic mechanism for the elimination of senescent or otherwise altered cells.

Figure 2

Aging and cancer: an ecological view. If an altered cell emerges in a normal tissue environment (left panel), it will be most likely cleared or kept at bay by mechanisms outlined in Figure 1. On the other hand, widespread alterations in the tissue environment, such as during aging (central panel), can select for the emergence of more fit, phenotypically normal cells, forming histologically normal clones. The combined presence of altered cellular phenotypes in an altered tissue environment (right panel) can set the stage for the evolution of neoplastic disease.