In these last few weeks leading up to my birthday, I’ve been thinking a lot about the concept of aging. It occurred to me how strange it is to consider how “old” or “young” I feel based on the number of years since my birth. After all, this is just my chronological age, and as the old saying goes, “age is just a number.” But does this number matter? Does my chronological age say anything about my biological age?
Undoubtedly, the two are correlated. As one ages, it becomes more and more difficult to maintain a youthful biological state. Simply put, the pure duration of time gives more opportunities for problems to arise. You may be thinking, of course, we all know that this is the inevitable process of aging, and that this is just how life works. We get old, and we develop certain problems which cause us to decline and eventually die.
What if this didn’t have to be the case? This classic sci-fi question may not be fiction forever. Several different observations and hypotheses have been made regarding so-called “hallmarks of aging,” or molecular signs of the aging process. While these presumed biological indicators of aging are wide-ranging and probably all valid, some of the most intriguing hallmarks concern the genome and the epigenome.
Figure 1: DNA methylation on cytosine bases. The structural formula of a single methylated cytosine is shown (left), as well as a generic representation of methylated DNA (right). (Image: Sigma-Aldrich)
Our genome refers to our DNA itself, the very genetic code that makes us who we are. It consists of a sequence of nitrogenous bases (A, C, T, and G) and encodes all of the materials and proteins necessary to make us. However, any gene in the genome can be turned on or off with certain molecular modifications, constituting our epigenome. In the context of this article, one of the most important modifications that can be made is called methylation, or the addition of a methyl group (-CH3) to a base in the DNA. Methylation interferes with DNA transcription into RNA, thereby “turning off” the expression of genes.
It is crucial that we have certain genes silenced and others activated in different cells of different tissues. For example, in our eye, we would want all of the genes for eye characteristics to be turned on, and all of the skin cell-specific genes to be turned off. This concept is known as tissue-specific expression, and it can become quite nuanced. The smallest cellular details being inappropriate for a certain tissue can have significant harmful effects, and it’s believed that this is one of the primary issues with aging.
At birth, we have a particular pattern of methylation in our epigenome, which should theoretically result in near-optimal cellular function. At this point, every tissue of the body has all the right genes turned on, and all the wrong genes turned off. As we age, we experience certain stresses on our cells that can cause DNA damage, eventually resulting in an unfavorable rearrangement of our epigenetic modifications. It slowly shifts further away from that ideal arrangement we’re born with, as more of the wrong genes get turned on and the right genes turned off.
David Sinclair, Professor of Genetics at Harvard Medical School, has done some remarkable research on this process. He describes how, as methylation patterns change, cells can get their “identities” confused. To go back to the earlier example, you wouldn’t want to turn on the wrong genes and have skin cells in your eye. Signs of aging don’t have to be quite this extreme to be harmful, but the general idea holds true.
A couple of really fascinating ideas emerge from the work of Sinclair and others on this epigenetic theory of aging. The first is that, if we know we’re born with this optimal configuration of methylated and unmethylated genes, then that opens up the possibility of restoring it later in life. Should our epigenome represent a significant mechanism of preserving our good health, doing this would in theory make us biologically “younger.”
The second is that we should also be able to get a pretty accurate idea of our biological age by measuring the difference in methylation of our epigenome in its current state and that we were born with. This is the main concept behind the Horvath aging clock developed by Steve Horvath, Professor of Genetics at the University of California, Los Angeles. This “clock” has demonstrated an impressive ability to predict biological age, producing results that correlate with a patient’s medical records.
A lot of lifestyle habits we discuss at Zone 7 have known mechanisms of modifying this clock, and allow us to slow the biological aging process. Though all of these molecular details will have to wait for future posts, this epigenetic theory of aging would appear to concretely show how these habits (exercise, sleep, caloric restriction, etc.) can improve longevity.
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