Is Epigenetic Disarray a Cause of Aging?

Your DNA is a blueprint for the protein components of the machinery of your metabolism and structure as a living organism. Gene expression is the process by which a part of the DNA blueprint is interpreted into instructions to build a protein, and epigenetics is the study of ways in which things other than changes in DNA can cause changes in gene expression. The blueprint may be the blueprint, but the execution of that blueprint is a shifting and very complicated process.

Epigenetics, it has to be said, is an unfolding and early-stage field. It's poorly understood. People are still arguing over whether accumulated nuclear DNA damage is significant in human aging, so of course it should be taken as read that there are also debates over whether epigenetic changes are significant in aging. Yes, the blueprint is getting smudged, and yes, the interpretation of that blueprint looks like it's changing - but is that actually important in comparison to the other known forms of age-related biochemical damage?

Here's a review:

Of all the proposed causes of ageing, DNA damage remains a leading, though still debated theory. Unlike most other types of age-related cellular damage, which can hypothetically be reversed, mutations in DNA are permanent. Such errors result in the accumulation of changes to RNA and protein sequences with age, and are tightly linked to cellular senescence and overall organ dysfunction.

Over the past few years, an additional, more global role has emerged for the contribution of DNA damage and genomic instability to the ageing process. We, and others have found that DNA damage and the concomitant repair process can induce genome-wide epigenetic changes, which may promote a variety of age-related transcriptional and functional changes. Here, we discuss the link between DNA damage, chromatin alterations and ageing, an interplay that explains how seemingly random DNA damage could manifest in predictable phenotypic changes that define ageing, changes that may ultimately be reversible.

With the present speed of progress, I doubt we'll be left hanging on a resolution to this debate for decades, awaiting data. Data is abundant in the life sciences nowadays. See this recent publication, for example:

Although the human genome sequence faithfully lists (almost) every single DNA base of the roughly 3 billion bases that make up a human genome, it doesn't tell biologists much about how its function is regulated. Now, researchers at the Salk Institute provide the first detailed map of the human epigenome, the layer of genetic control beyond the regulation inherent in the sequence of the genes themselves.

...

Being able to create high resolutions maps of the human epigenome, Ecker's group will now begin to examine how it changes during normal development as well as examining a variety of disease states. "For the first time, we will be able to see the fine details of how DNA methylation changes in stem cells and other cells as they grow and develop into new cell types," he says. "We believe this knowledge will be extremely valuable for understanding diseases such as cancer and possibly even mental disorders. Right now we just don't know how the epigenome changes during the aging process or how the epigenome is impacted by our environment or diet."

What interesting times we live in. You might recall the circus of triumph that surrounded the Human Genome Project at the turn of the century, but less than ten years later, mapping large segments of the epigenome merits a minor press release and little notice. How fast things do move, thanks to the ferociously competitive market for computing power.

ResearchBlogging.orgSinclair DA, & Oberdoerffer P (2009). The ageing epigenome: damaged beyond repair? Ageing research reviews, 8 (3), 189-98 PMID: 19439199

Comments

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.