More on DNA Methylation and Aging

DNA methylation is a part of epigenetics, one of the mechanisms by which protein machinery produced from DNA creates feedback loops to change the production levels of many different proteins. Genes are decorated with a continually altering array of chemical signals, changing with circumstances and environment. The cell nucleus is a factory, DNA the component blueprints, and DNA methylation one portion of the chaotic parts order list: from moment to moment, how much to make of each piece of protein machinery encoded in the genome.

DNA methylation changes with age, location within the body, and type of cell, a fuzzy and very complicated pattern of decorated genes. Some of the myriad changes are sufficiently similar from person to person to be a possible method to determine age quite accurately. Others are known to reflect the degree to which a person becomes frail with age. Many more are not understood at all, or may be largely random.

A great many debates within aging science revolve around the difference between cause and consequence - and so too with DNA methylation. Is it a part of the expected attempts by the body to adapt to increasing levels of cellular damage caused by aging, or is at least some alteration in DNA methylation a form of damage in and of itself? Good arguments can be made either way, but for my money I'd be surprised to see significant levels of epigenetic changes that were anything other than the results of underlying damage and evolutionary adaptations that try (and ultimately fail) to cope with that damage.

This debate is significant, of course, because of how it directs research and development funding. Will scientists try to patch over the root causes of aging by altering its secondary effects - inevitably doomed to be expensive and comparatively ineffective - or will they work to repair the true causes, and thereby remove the secondary effects for free? There's been a great deal too much work on patching over the cracks in the medicine of past decades, and in this age of biotechnology it seems a sin to continue that way when we don't have to.

In any case, here is news of more recent work on DNA methylation that has been doing the rounds:

DNA Switches Discovered to Decline Significantly with Age

An important element of the DNA is what is known as the epigenome. This refers to the pattern of added chemical tags on the DNA called methyl groups. These tags may alter the expression of genes near or on which they reside. Usually they turn off expression of the gene on which they reside.


A team of researchers decoded and compared the entire epigenome from blood cells in a neonate, a 26 year old, and a 103 year old. The results were striking. The researchers discovered that as the cells aged, the epigenome changed dramatically. They found 80% of all cysteine residues were methylated in the newborn compared to just 73% of them in the centenarian. A 26 year old subject had 78% of them methylated. They also found almost 18,000 locations in the genome where methylation varied the most. About one third of those regions occurred in genes linked to increase risk of cancer. Mostly aging involved loss of methyl groups.

Why do we age? Genomes of baby and 103-year-old may offer clue

The researchers analyzed the genome of the baby's white blood cells (obtained from cord blood). They found more than 16 million spots where methyl groups had been attached to the baby's DNA. But when they did the same thing with the old man's DNA (obtained from his white blood cells), they found nearly 500,000 fewer sites with methyl groups attached. The sites weren't as densely methylated either.

The scientists got a similar result when they looked in a larger group of 19 Caucasian newborns and 19 Caucasian nonogarians (average age 92.6). And they found an intermediate level of methylation when they examined the white-blood-cell DNA of 19 middle-aged people (average age about 60).

The scientists went on to take a closer look at a few specific genes where they'd spotted changes in methylation in their samples and found that the activity of the genes that had been depleted in methyl groups was, indeed, changed. And they noted that some of the genes - such as two called Sirtuin 5 and Sirtuin 7 - are thought from other studies to be involved in the biology of aging.

As I said above, I don't think epigenetic changes have much to say about why we age, as they are not a fundamental change. They may encode many of the details of how we age, however - ways in which low-level damage translates into characteristic changes in the way that cells, systems, and organs operate. This may be very valuable, but equally it doesn't change the basic goal, which is to repair the fundamental forms of damage that drive aging.


I realize this is an older thread, but I am wondering if there is any impact in using methylated b-vitamins. I take a methylated B-complex because I have MTHFR. Is this positive, negative or neutral in terms of aging?

Thank you

Posted by: K at January 12th, 2021 5:56 AM
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