A form of inherited gene regulation known as parental imprinting, which was originally thought to be maintained in a stable form by the body, may actually be more dynamic. This form of inherited methylation may actually contribute to changes in the brain and other tissue that occur during aging and human development.
In Brief: Inherited Methylation
“Methylation” refers to when a molecule is attached to DNA to affect how it governs gene expression. You inherit DNA from your parents, but you can also inherit methylation that DNA undergoes during either sperm and egg cell formation or after fertilization. This is known as “parental imprinting”. Methylation can change over time as genes are turned on and off, but the methylation from inheritance was thought to be largely stable. It was believed that the body would try and maintain these methylated elements rather than dynamically regulate them.
Although gene mapping technology has improved over the years, it is largely only able to take “snapshots” of genes and methylation. This makes tracking ongoing changes difficult. The researchers wanted to see if they could track potential changes in inherited methylation, so they devised a sort of reporter and marker system that could monitor individual cells in real-time.
The simplified version of how this worked is that a “reporter” was inserted into the cell and tied to the gene the researchers wanted to look at. When the gene was methylated (“inactive”), so was the reporter. When the gene was un-methylated (“active”), the reporter was as well, and the active reporter would then glow.
Through this method, the researchers found that the inherited methylation was being actively regulated throughout development and into adulthood. The fact that some of these imprints were in neural cells meant that parental imprinting could potentially have a role in the shaping of the adult brain.
What This Means
To say that gene regulation is complicated is a spectacular understatement. It is a complex dance of intertwining factors that are not always intuitive or obvious. The idea that inherited methylation could be actively regulated and have a role in aging is one thing, finding a way to determine whether this is true or what kind of role is another. Right now, the research is basically at the stage of “we have this neat thing, but no idea what it means”. Understanding the consequences and implications of parental imprinting, on aging or anything else in the body, will take time and dedication.
“Inherited Parental Methylation Shifts over Time, May Have Functional Effects in the Brain and Other Tissues,” Whitehead Institute web site, September 20, 2016; http://wi.mit.edu/news/archive/2016/inherited-parental-methylation-shifts-over-time-may-have-functional-effects-brain, last accessed September 21, 2016.
Stelzer, Y., et al., “Parent-of-Origin DNA Methylation Dynamics during Mouse Development,” Cell Reports, 2016; http://dx.doi.org/10.1016/j.celrep.2016.08.066