Hallmarks of Aging: Telomere Attrition

Hallmarks of Aging: Telomere Attrition

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

  • What telomere attrition is
  • Why it happens
  • The consequences of telomere attrition

The Hallmarks of Aging describes telomere attrition as the erosion of the protective telomeres that cap the ends of our chromosomes. This gradual shortening of the telomeres is thought to be one of the reasons we age and is linked to a number of age-related diseases including idiopathic pulmonary fibrosis.

Telomeres perform two broad functions: a protective cap and an aging clock. Don’t worry–it’s not as complicated as it sounds (ok, maybe a little).

Protecting the DNA from damage

The building blocks of our DNA are very good at bonding with each other, which is useful on one hand, but is also dangerous on the other. For example, a chromosome could bond with another chromosome, or it could even bond to something completely different!

Fortunately, our cells have an answer to this problem. Our chromosomes which store our genetic code are protected at each end by a cap-like structure known as a telomere. This structure is actually a specific DNA sequence that is repeated thousands of times and stops our DNA from unraveling, kind of like an aglet on the end of a shoelace or the cap on the end of a pen.

Because the cap bonds to DNA like an opposing DNA strand would, via the base pairs, the chromosomes must be the same. Otherwise, each chromosome would need a unique cap and a mutation to the end of a gene could potentially lead to a chromosome fraying. The sequence in the telomere caps does nothing but signal that it is the end of the chromosome and so avoids this issue.

Finally, DNA damage can change one pair to another. This is more likely to happen at the exposed end of a chromosome.

As a final method of protection, every time a chromosome is copied, the DNA is a bit shorter. Having a non coding sequence at the end means that section can shorten without altering the function of the coding DNA.

They are also an aging clock

Telomeres are also a kind of “aging clock” and with each division of a cell the telomeres shorten. An enzyme called telomerase can reverse that shortening but this only normally happens in our germline and some stem cells.

Normal (somatic) cells do not have access to telomerase so they cannot restore the lost repeats on the ends of their chromosomes. Ultimately this means that each division makes the telomeres shorter and shorter. Once it becomes critically short the cell stops dividing and enters cellular senescence, a state where the cell shuts down and destroys itself.

This cellular clock is thought to be an anti-cancer measure to remove old and potentially damaged cells from the system. Also, if all our somatic cells had access to telomerase it could open the door to cancer, so this is why in most cells it is turned off.

Normally this safety measure is a positive thing, but as we grow older more and more cells reach this replicative limit. This ultimately means there are no new cells to replace those lost which leads to tissue and organ failure.

What causes telomere attrition?

  • Oxidative stress
  • Chronic inflammation
  • Exposure to infectious agents
  • Cell division

Oxidative stress there have been a number of studies suggesting that oxidative stress is associated with accelerated telomere shortening and dysfunction. This is a problem as not only can the environment provoke oxidative stress, but our own metabolism can generate it as a byproduct of its normal operation.

Chronic inflammation is also associated with telomere attrition. As we age the level of persistent inflammation from sources such as senescent cells, immune system dysfunction and more, typically rises. This smoldering background of inflammation is often referred to as “inflammaging” and contributes to the shortening of telomeres.

Exposure to infectious agents is another way in which telomeres can be shortened. Exposure to Salmonella and other infectious agents has been associated with faster telomere erosion.

Cell division is also another way in which telomeres shorten. With each new cell division, the telomeres shorten in all our cells with the exception of germline and some stem cells.

What can we do about telomere attrition?

There are a number of approaches being developed by researchers to restore lost telomeres and there are even things you can do yourself to potentially help.

  • Good lifestyle choices such as healthy diet, exercise, and meditation
  • Inserting extra copies of the telomerase gene into the DNA
  • Transient induction of telomerase gene using drugs
  • Injecting telomerase RNA into cells to transiently induce telomerase

Successfully slowing down how fast our telomeres erode, or even replacing those losses, could help reduce our risk for developing diseases such as fibrosis and keep our organs and tissues healthy.