Changes in DNA and Aging

Do changes in nuclear DNA significantly affect the course of aging? A good question, and one that is still open and energetically debated in the scientific community. How about epigenetic changes, mechanisms that alter the process of producing proteins from genetic blueprints without changing the genes themselves, such as those involving DNA methylation? Insofar as degenerative aging is concerned, are epigenetic changes a cause, a consequence of other, more fundamental changes, or a mix of both cases? These are also good questions, and still open to debate or new evidence.

I noticed two open access papers on epigenetic changes in aging today, the first of which begins with this statement:

Aging is arguably the most familiar yet least-well understood aspect of human biology.

Which is quite true. Fully understanding aging - a set of massively complex changes in a massively complex system - will take a long time, biotechnology revolution or no biotechnology revolution. But full understanding is not needed for significant progress to occur in the development of medical technologies to repair and reverse the damage of aging. Just as for other fields, there are engineering strategies that can sidestep ignorance and build good solutions based upon what is actually known. Our ancestors built good, working bridges for thousands of years prior to the advent of modern architectural and materials science, for example - they didn't have a full understanding, yet got the job done by forging ahead and building upon what they did know. Today, life science researchers know more than enough about the forms of damage caused by aging to proceed with development: it is perfectly possible to work towards biological repair in the absence of a complete understanding of all the interactions and processes of aging. Fixing the damage we see will be sufficient - we don't have to fully understand all of the very complicated ways that this damage progresses into disease and death.

But take a look at the papers - I think you'll find them an interesting example of an open and debated question in aging science.

The Janus face of DNA methylation in aging

The role of epigenetics in aging and age-related diseases has gained interest given recent advances in the understanding of how epigenetic mechanisms mediate the interactions between the environment and the genetic blueprint. While current concepts generally view global deteriorations of epigenetic marks to insidiously impair cellular and molecular functions, an active role for epigenetic changes in aging has so far received little attention.

In this regard, we have recently shown that early-life adversity induced specific changes in DNA methylation that were protected from an age-associated erasure and correlated with a phenotype well-known to increase the risk for age-related mental disorders. This finding strengthens the idea that DNA (de-)methylation is controlled by multiple mechanisms that might fulfill different, and partly contrasting, roles in the aging process.

Age-associated epigenetic modifications in human DNA increase its immunogenicity

Chronic inflammation, increased reactivity to self-antigens and incidences of cancer are hallmarks of aging. However, the underlying mechanisms are not well understood. Age-associated alterations in the DNA either due to oxidative damage, defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible. Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells.

...

Investigations into the mechanisms revealed that DNA from aged subjects is not degraded, neither is it more damaged compared to DNA from young subjects. However, there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity. Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation, autoimmunity and cancer.

In the context of that second paper, you might firstly look at a recent post on age-related damage to the innate immune system. Very little if anything in our biochemistry changes in isolation. Secondly, you should wander back into the Fight Aging! archives for a refresher on why chronic inflammation in aging is such a bad thing:

ResearchBlogging.orgMurgatroyd C, Wu Y, Bockmühl Y, & Spengler D (2010). The Janus face of DNA methylation in aging. Aging, 2 (2), 107-10 PMID: 20354272

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