December 7, 2021

I, Science

The science magazine of Imperial College

This is the story of how telomeres determine our lifespan, but can they help 'cure' aging? ...


More and more scientists are starting to approach aging as a ‘disease’ that can be ‘cured’. Can this be done? What makes aging so different from other diseases? In fact, what even is aging and why does it have to happen?

Aging is complicated. It happens for many reasons, but essentially over time cells accumulate damage causing our body to physiologically malfunction. Why can’t the body simply renew the damaged cells?

The truth is that almost all of the cells in our body have a finite lifespan. They are programmed to die one day.

Although there are many biological avenues to discuss how and why this happens, in this blog I will (briefly) discuss the remarkable structure called the telomere. Telomeres consist of the bases ‘TTAGGG’ repeated thousands of times at the ends of your chromosomes. These repeats then loop round like a lasso to create a ‘T-loop’ structure.

Telomeres, apart from being exceptionally fascinating, are hugely relevant to aging. In a sense, they are like the little plastic caps on the ends of your shoe laces. They are at the ends of your chromosomes to prevent the DNA (your shoe laces) from fraying; keeping your DNA intact.

Our DNA is linear, and every time the cell divides a piece of DNA is lost from the end of the chromosome (due to the way in which DNA replication proteins function). So without special protection, the telomeres would shorten, fray and break. This is known as ‘telomere attrition’, and occurs when the telomeres lose their protective structure causing chromosome ends to become sticky and fuse to one another, generating genomic instability and gene miss-regulation, leading to cellular ageing and disease.

When telomeres shorten in humans, they send a WARNING signal to the rest of the cell, and the cell begins to senesce: gene expression changes and the cell secretes factors that cause age-related diseases. Much like a candle slowly burning down until the flame goes out, our telomeres shorten as we age.

So essentially, the older you are, the shorter your telomeres. There are other factors that telomere length has been shown to correlate with. For example, those who smoke are more likely to have shorter telomeres for their age, as are those who have experienced immense stress in their life such as childhood trauma, major depression or domestic abuse. Even for babies in the womb whose mothers have experienced immense stress, life is dished out with shorter telomeres.

On the flipside, those who exercise and have reduced stress are more likely to have longer telomeres for their age. Weirdly, greater telomere length in older men and women is even associated with higher educational achievements (and this is after being adjusted for health, income and jobs).

However, for some of our cells, the telomeres do not shorten. These cells are immortal. Our germ cells (those that produce eggs and sperm) and our stem cells are part of this small but significant immortal community. These cells contain a significant abundance of the enzyme telomerase, which is able to extend the telomere length by adding additional copies of the telomere repeat TTAGGG. Why can’t all of our cells have telomerase so we might have a chance of living forever?

There is a very good reason why our cells have evolved to have shortening telomeres. All cancer cells are immortal, and they achieve this by mutating in such a way that allows them to retain their telomere length. Most cancers have reactivated telomerase, allowing them to surpass aging, divide and spread.

So yes, our telomeres shorten and we grow old. But rather that than cancer, right? The abundance of telomerase is exquisitely controlled in our cells by the surrounding biological machinery. You could say that telomerase levels are balanced on a knife edge; increasing telomerase abundance and decreasing it both lead to diseases such as cancer. Although many scientific groups are researching ways to increase telomerase expression to perhaps allow us to keep longer telomerase into older age, I certainly would not let anyone fiddle with my telomerase levels.

How can telomeres help us? We now know that we expect telomere shortness to precede and predict the diseases of aging. Measuring telomere length may thus allow future generations to pre-empt, intercept and even prevent age-related diseases.

IMAGE: Chromosome with telomeres highlighted in green. Courtesy of Dr Joseph Raffaele, co-founder of PhysioAge Medical Group