Intro to Epigenetics and How it’s Connected to Aging
Shoutout @etc.9625! Keep sending me article ideas everyone :))
Epigenetic changes are changes in genetic material that don't result from DNA sequence, but rather from chemical and physical modifications impacting the DNA's structure.
DNA can be directly methylated, which suppresses DNA expression. A cool example of DNA methylation's effects on gene expression is genetic imprinting, which is how the genes from one parent are expressed and the other suppressed (via methylation). Here's an article I wrote about imprinting a while back, although the PWS/AS section at the end is slightly scuffed: https://www.sixfootscience.com/brain-snips/how-genetic-imprinting-works-mechanisms-and-diseases.
Histone modifications are another common epigenetic change. Histones are proteins that DNA is wrapped around to condense vast amounts of genetic material into the tiny nucleus. There are various levels of wrapping, diagrammed below.
Commonly discussed histone modifications include acetylation (addition of a COCH3 group), phosphorylation (addition of a PO3 2- group), methylation (addition of a CH3 group), and ubiquitylation (addition of a ubiquitin protein). Because acetyl and phosphoryl groups are polar and negatively charged, they mask the positive charge of histones, and the negatively-charged DNA is no longer attracted to histones. By contrast, addition of the uncharged methyl or ubiquityl groups re-strengthens the histone-DNA ionic attraction by occupying the acetyl/phosphoryl's spot. Point is, acetylation and phosphorylation loosen up the DNA and free up space for transcriptional enzymes, while methylation and ubiquitylation recondense the DNA.
All these epigenetic modifications and different states of chromatin (DNA+histones) condensation have important implications on aging. Harvard researchers have discovered that DNA breakage and repair drive aging symptoms. Each time repair enzymes try to fix a DNA break, the DNA has to loosen up locally to allow the enzymes to come through. Because break repair requires epigenetic changes, frequent breaks, or many breaks accumulating over time, can mess with chromatin structure. This contributes to the symptoms of aging. In the mouse studies of this experiment, researchers found that even cumulative DNA break-induced chromatin changes in introns (DNA sequences that don't code for protein; opposite are exons) resulted in aging symptoms. Thus, it doesn't matter if the chromatin changes in a coding or noncoding region; changes in the structure of genetic material contribute to aging. The mechanisms behind this are still under study. Additionally, there are many other factors being studied relating to epigenetics' effects on aging, including lifestyle (on a related note, pls drop LyfëStyle, Yeat), histone properties (which are very well evolutionarily conserved, so altering these is very interesting), and more.
To learn more about this topic, please visit the links below. Thanks <3
Harvard researchers' experiment video: https://youtu.be/PYjPqq8P70s.
Article on effects of lifestyle on epigenetics of aging: https://www.nature.com/articles/s41392-022-01211-8.
Another article about epigenetics and aging: https://www.science.org/doi/10.1126/sciadv.1600584.
