The Study of Chromatin in the Context of Aging
Chromatin is the bundled, packaged form of DNA found in the cell nucleus. The behavior of a cell depends on the precise details of the structure adopted by chromatin, because only exposed sequences of DNA can be used to produce proteins - the rest is hidden from the machinery of gene expression. The produced proteins can then lead to adjustments to chromatin structure, and thus a cell is in a constant state of change and feedback between chromatin structure, gene expression, protein activities, and the surrounding environment. Talking about chromatin structure in the context of aging is a very broad topic, much akin to talking about gene expression in the context of aging. Clearly there are changes, a lot of them. Clearly it is very complex. One can still find starting points for a discussion, however.
Chromatin provides an interface between genetic information and the environment, allowing an individual's experiences to shape the course of their life from within their cells. In order to store and protect genetic material, DNA is wrapped around histone proteins inside the nucleus, and this bundle of DNA and histones is termed chromatin. Histones do more than simply package DNA however, as the level of accessibility versus condensation of chromatin can impact the availability of DNA to binding by transcriptional machinery and therefore the expression of genes.
Aging affects nearly all aspects of our cells, from our DNA to our proteins to how our cells handle stress and communicate with each other. Age-related chromatin changes are of particular interest because chromatin can dynamically respond to the cellular and organismal environment, and many modifications at chromatin are reversible. Changes at chromatin occur during aging, and evidence from model organisms suggests that chromatin factors could play a role in modulating the aging process itself, as altering proteins that work at chromatin often affect the lifespan of yeast, worms, flies, and mice. The field of chromatin and aging is rapidly expanding, and high-resolution genomics tools make it possible to survey the chromatin environment or track chromatin factors implicated in longevity with precision that was not previously possible.
In this review, we discuss the state of chromatin and aging research. We include examples from yeast, Drosophila, mice, and humans, but we particularly focus on the commonly used aging model, the worm Caenorhabditis elegans, in which there are many examples of chromatin factors that modulate longevity. We include evidence of both age-related changes to chromatin and evidence of specific chromatin factors linked to longevity in core histones, nuclear architecture, chromatin remodeling, and histone modifications.