Why Do We Age? | Telomere Shortening

Telomeres are pieces of repetitive DNA at the end of our DNA strands. Telomeres prevent the DNA strands from fraying. With each cell division, telomeres become shorter.

The Threads of Life

Telomeres are short pieces at the end of our chromosomes.

You can compare telomeres to the caps on our shoelaces that prevent the laces from raveling out.

With every cell division, telomeres become shorter. When they are too short, cells stop dividing. These cells cannot continue supporting and forming our tissues properly.

When after many cell divisions the telomeres have become too short, the DNA strand starts to unravel: it becomes unstable, leading to damage to the cell. 

Too short telomeres also send out several “damage signals” to the cell, which then starts to function less properly.

You can look at telomeres as a clock that ticks down with every cell division until the time is up. 

The roles of telomeres in aging: misconceptions and outdated ideas

Given that during aging telomeres become shorter after each cell division, it was assumed that telomere length could tell you something about your remaining lifespan. The shorter your telomeres, the less long you would live. 

However, various studies showed that there is no clear correlation between telomere length and lifespan (R). 

Which is not surprising. Mice for example have telomeres that are ten times longer than humans. But mice don’t live ten times longer than humans. 

These insights led a lot of people to believe that telomere length is not important in aging. 

However, studies show that the speed at which telomeres shorten is significantly correlated with the rate of aging (R). In other words:

It’s not telomere length, it’s telomere lengthening that matters in aging

Telomere length is not correlated with lifespan, but the rate at which telomeres shorten is. 

To give a concrete example: mice have telomeres that are much longer than telomeres in human cells. But given that mice telomeres shorten much faster than human telomeres, these little critters age much faster. 

Another misconception is the idea that there are cells in the body that hardly divide (like muscle cells or brain cells), so their telomeres do not really become shorter, but still these cells age.

That is true, but during aging, the telomeres still become damaged (without really becoming shorter), which also contributes to cellular dysfunction. 

Secondly, there are many dividing cells surrounding and supporting the non-dividing brain cells or muscle cells, such as blood vessel cells, fibrous tissue cells, macrophages, and glial cells (these cells support and nurture the brain cells). If these supporting cells become older because of telomere shortening due to their divisions, they will start to malfunction, leading to damage to the non-dividing brain cells or muscle cells. 

Does increasing telomeres increase the risk of cancer?

Another misconception is that lengthening telomeres will automatically result in an increased risk of cancer.

After all, cancer cells are immortal cells that can keep dividing thanks to their ability to lengthen their telomeres with the aid of an enzyme called telomerase.

Studies have indeed shown that in mice with upregulated telomerase there is an increased risk of cancer. 

However, in these studies the telomerase was continuously activated since birth. This results in continuous, uncontrolled telomere activity.

On the other hand, other studies show that if the telomerase is upregulated in adult mice only occasionally, the mice live longer and do not have an increased risk of cancer (R,R).

In other words, upregulating telomerase in a facultative (now and then) manner instead of in a constitutional (continuous) way does not lead to an increased risk of cancer.

Lengthening telomeres could even lead to a decreased risk of cancer given that too short telomeres lead to genetic instability which can in fact increase the risk of cancer. 

Other studies showed that mice with very long telomeres live longer and don’t have an increased risk of cancer (R). In these mice, the telomere activity was not increased, they had extra long telomeres since birth. 

Some people are born with genetic mutations leading to short telomeres. These are diseases like pulmonary fibrosis, aplastic anemia, and dyskeratosis congenita.

These people suffer from problems with the immune system (white blood cells are fast dividing cells of which the telomeres grow short quickly), hair and nails (also fast dividing tissues) and the blood cell formations (the stem cells that create blood cells divide very fast; every second two million red blood cells are created).

Such observations suggest that telomere shortening is especially important for fast dividing cells, like the stem cells that generate white blood cells, red blood cells, hair, and skin cells. 

Another example: Shortly after fertilization of the egg cell by a sperm cell, the telomeres of the embryo are lengthened very significantly, without increasing the risk of cancer.

Also, exercise, healthy food and stress reduction all lengthen telomeres, but these interventions do not increase the risk of cancer, in fact, they decrease cancer risk.

Furthermore, it’s important to note that exercise, nutrition and supplements (like lithium, pterostilbene or magnesium) can extend telomeres somewhat, but far less and far less continuous than via genetic constitutional upregulation of telomerase.

Anyhow, more recent research is putting to rest the outdated idea that lengthening telomeres always automatically leads to more cancer risk.

Lengthening telomeres can sometimes even protect against cancer, enable more genetic stability, or increase lifespan and health span without increasing cancer risk.

NOVOS’ Approach to Telomere Shortening