Hallmarks of Aging: Epigenetic Alterations

Hallmarks of Aging: Epigenetic Alterations

Quick overview of what you’ll learn from this blog post:

  • What are epigenetic alterations?
  • What causes epigenetic alterations?
  • What are the consequences of epigenetic alterations?

Epigenetic alterations are described in the Hallmarks of Aging as age-related changes in gene expression that harm cellular function and increase the risk of cancer and other age-related diseases.

Changes to gene expression drives the aging process

Every single cell in our bodies have the same DNA but they often look and function very differently. So why is that?

The reason is that various alterations in our cells happen that change the expression of our genes, without changing their contents. Gene expression varies between cell types which causes them to produce different proteins and allows them to perform different functions.

So once a cell has settled into its role and become the correct cell type, its gene expression profile becomes fixed. This means that its daughter cells also have the same gene expression and remain the same cell type as its parent. This is what lets liver cells stay as liver cells, kidney cells stay kidney cells, brain cells to remain brain cells, and so on.

Unfortunately, as we age these established gene expression patterns begin to change. A gene can be turned on or off and that change will then be passed down to the next generation of cells too. These changes gradually mean that daughter cells begin to stop resembling their parent cell as closely.

They can develop new epigenetic alterations and lose old ones. This means that these cells can start producing proteins that are unsuited for the type of cell or loose proteins needed for the cell to function properly.

How do epigenetic alterations happen?

Epigenetic alterations can occur in various ways, the most common ways are:

  • Changes to methylation state
  • Histone modifications
  • Non-coding RNA
  • Telomere shortening
  • Increased transcriptional noise

Changes to methylation state are frequently how epigenetic alterations can happen. This is a biological process where methyl groups are added to or removed from the DNA molecule. A methyl group is a small molecule made from one carbon and three hydrogen atoms. Generally speaking, methylation turns genes “off” and demethylation turns genes “on” and can change how proteins behave.

These changes to methylation state can lead to a number of serious consequences. For example, if tumor suppressing genes become methylated, it opens the door for cancer to develop. In the case of demethylation, it can cause a loss of chromosomal stability which again paves the way for cancer.

Histone modification is another way in which epigenetic alterations can happen. Histones are spherical shaped proteins that our DNA wraps around to form the chromosomes. For gene expression to happen the wrapped DNA must be unwound.

Changes to the histones can sometimes prevent the DNA from unwinding and stops gene expression from happening. Turning off genes can lead to dire consequences if the particular gene is producing proteins critical to the cell’s function.

Non-coding RNA is another way in which changes occur. It serves as a messenger and acts as a copy of a gene to facilitate protein production during a process called translation. However, some DNA is recorded as RNA but does not get translated, this is a problem as some RNA sequences regulate gene expression.

Telomere shortening is also another way in which epigenetic alterations can happen. Originally thought to be just a biological clock controlling the number of times a cell can divide, new evidence suggests they do more than this.

They also up and down regulate gene expression, both near to and further away from the telomeres. Some of the genes they influence include ISG15, which relates to antiviral defense response and C1S, which is also involved in the immune system.

Over time as telomeres shorten their regulation of gene expression also changes and it is those changes that are believed to contribute to epigenetic alterations. It also highlights just how interconnected the aging hallmarks are and that one influences another as we age.

Increased transcriptional noise, a primary cause of variance in the gene expression happening between cells, can lead to epigenetic alterations. Transcriptional noise can cause genes to be interpreted differently depending on its level which can again lead to incorrect protein production and other dysfunctional behavior.

Various lifestyle factors have been identified that likely negatively change epigenetic patterns, such as poor diet, obesity, lack of physical activity, smoking, alcohol consumption, environmental pollution, psychological stress, and working night shifts.

There are a number of age-related diseases linked to epigenetic alterations, though cancer is probably the most well-known.

What can we do about epigenetic alterations?

Researchers are testing a number of approaches which might help to address epigenetic alterations. There is also some evidence suggesting that caloric restriction may slow down the rate of epigenetic alterations.

  • Partial cellular reprogramming to reverse epigenetic alterations
  • Fasting or caloric restriction to slow the rate of change

Epigenetic alterations appear to play a key role in the aging process. Therapies that can slow or even reverse the rate at which these changes happen have huge potential to increase healthy human lifespans.