Aging by epigenetics--a consequence of chromatin damage?

Abstract

Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases.

Figure 1. A model depicting the proposed impact of heterochromatin on longevity of mammals

Considerable evidence, discussed in the text, supports the idea that heterochromatin redistributes in cells during cellular and organismal aging. The primary purpose of this redistribution might be to extend longevity by promoting tumor suppression (green arrows). According to the idea of antagonistic pleiotropy, this will also lead to decreased renewal of adult tissue stem cells and renewable tissues, and consequently tissue aging (blue arrows). Stochastic errors in the redistribution of heterochromatin (e.g. excessive spreading of heterochromatin along chromosomes) might lead to erroneous silencing of other genes, e.g. tumor suppressor genes. In this case, redistributed heterochromatin will tend to decrease longevity (thin black lines). Actual organismal longevity will ultimately be determined by the balance between these competing processes.