Epigenetic Alterations: Change Is Inevitable – Part 1
Dear Longevity Insider,
Change is inevitable, but your choices can alter the path.
Epigenetics literally means "above genetics." Epigenetics can’t change your DNA, but it has the potential to change the way your genes are expressed.
Epigenetics is one of my favorite topics. I have written about different aspects of epigenetics in the past. This week, we will explore the more technical side of the third hallmark of aging, epigenetic alterations, and how it contributes to the acceleration of aging.
In their landmark paper, The Hallmarks of Aging, Lopez-Ortiz et al composed three requisites and criteria that each hallmark should fulfill: “(i) it should manifest during normal aging; (ii) it’s experimental aggravation should accelerate aging; and (iii) its experimental amelioration should retard the normal aging process and, hence, increase healthy lifespan.” While each of the nine hallmarks meets these criteria in varying degrees, epigenetic alterations give us significant examples of all three.
Our DNA’s Package
Before we elaborate, we must delve a little deeper into our biology lessons to get to the foundation of this hallmark of aging.
If you took a single DNA molecule and spread it out in a linear fashion, it would measure about six feet in length! In a human cell, this must be packaged into the nucleus of a cell with a diameter less than a human hair. So it goes without saying that our bodies have to do some pretty miraculous work to fit 46 of our 6-foot DNA molecules into the nucleus of every cell. And remember, we have approximately 30-40 trillion cells in our bodies!
In order to do this, the DNA must obviously be condensed. We’ve mentioned that our double-helix DNA is tightly woven around proteins. These proteins are called histones, and our cells wrap about 150 base pairs of DNA around a group of eight of these histones together – known as the histone octamer – to form what’s called the nucleosome. These resemble beads on a string, and they continuously spiral to form what’s known as the solenoid, which then supercoils further and stacks together to form a single fiber known as the chromatin. The end result is compacted DNA, histones, and a percentage of RNA, and the final condensed structure of this process results in the chromosome.
Chromatin is important because it strengthens the DNA to withstand cell division. It also allows for DNA replication, transcription (the process of making an RNA copy of a gene’s DNA sequence), DNA repair, and genetic recombination (diversity).
Our Genetic On/Off Switch
There are many epigenetic alterations that affect our cells throughout our lifetime. The first change is what has been observed in DNA methylation patterns.
Remember that DNA is made up of nucleotide bases that form pairs of adenine (A), guanine (G), thymine (T), and cytosine (C), which in turn spell out our genetic code. One way that the body regulates how those genes are expressed is through a process called methylation. DNA can be tagged, or marked, with tiny molecules called methyl groups at some of its cytosine (C) locations. Like a switch, this literally silences that section of the gene, which can allow for normal cellular differentiation when we are developing as a fetus.
As we age, methylation can be thought of as a way for DNA to adapt to the never-ending changes in our environment – for better or for worse. The methyl groups need to be in the right place at the right time. It is when the methylation patterns become disrupted that things start to go awry. For example, some cancer cells are known for methylating areas of the DNA that are usually protected, and vice versa, which ultimately leads to abnormal suppression of activity in our DNA and thus, our gene expression.
On Thursday, we'll dive into our "genetic volume control."
To your longevity,
Anil Bajnath MD
CEO/Founder, Institute for Human Optimization
Chief Medical Officer, Longevity Insider HQ
P.S. Here is my most prized research on genes and aging.