TELOMERES AND AGING

Telomeres form the ends of human chromosomes and protect the chromosome from damage.

Think of telomeres like the plastic caps on the end of shoelaces: if the plastic caps break, the shoelace frays. It’s the
same for our DNA. In human cells, the length of the telomere shortens a small amount each time the cell divides.

Figure 1. Left to right: Schematic image showing a human cell with DNA within the nucleus; zoomed image showing a
chromosome with telomere caps; cell division and associated gradual shortening of the protective telomere cap.

So over time when your DNA keeps dividing over and over the telomeres shorten and you get less gene expression
which basically means you're getting less activation of certain genes especially related to repair so when you're very
young your DNA inside your cells have a huge capacity to keep up with the damage when you're older because you
have less telomeres you basically have a hard time keeping up with a repair and that's how it relates to aging.

So telomeres shorten with each cell division, but they also get shorter as you age. Like, even when you’re producing
new cells, your telomeres are now shorter than they once were when you were younger, a trend called ‘telomere
attrition’. This means that your chromosomes are less protected from damage during cell replication. Which is what
scientists believe could be behind the decreased function and wellness of our bodies as we age, and could lead to
degenerative diseases like Alzheimer’s. This info may now have you wondering, what do I have to do to keep my
telomeres from shortening as I age?' On a certain level, there may not be much you can do about it. Your telomeres’
length and how fast they shorten throughout your lifetime is highly variable. Estimates say anywhere from 30-80% of
your telomere’s characteristics could be due to genetic factors and other things out of your control like your father’s
age at the time you were conceived. But, there’s good news: there are some things under our control. While
telomeres are the protectors of our DNA, they are also very susceptible to damage themselves by—most notably—
stress. Stress is an ambiguous word, but can come in a multitude of forms: smoking, obesity, exposure to trauma, a
psychological disorder like major depression, and so much more, all of which can lead to physical effects like higher
levels of stress hormones and the presence of inflammation. Which are associated with acceleration of telomere
shortening. And as we’ve already established, telomere shortening is not good for your health. Just thinking about
telomere shortening is stressing me out and probably shortening my telomeres! Man, I really need to get more
sleep. Exercising, staying away from cigarettes, doing what you can to destress might actually add years to your life
in the form of telomere length preservation. But saving your telomeres from excess shortening won’t necessarily
save you from the things you’re genetically predisposed for. It just means they may happen to you later, rather than
sooner. And aside from making good lifestyle choices, there may be something we can take advantage of to lengthen
our telomeres built right into our cellular machinery. Telomerase is an enzyme that lengthens telomeres.
In our adult stem cells, which is where new cells in our body come from, and our germ cells, which make sperm and
eggs, telomerase is busy building those telomeres back up. If we could somehow get telomerase to build back the
telomeres in our somatic cells, our regular body cells, that would be great! But the problem is that turning
telomerase on is actually associated with cancer because, again, cells aren’t meant to just replicate forever and if
they do, it can be a problem.

Now how do you explain cancer cells that can live forever well they produce an enzyme called telomerase which can
counter this shortening effect so a telomerase is an enzyme that allows for the replacement of these short bits of
DNA.

After many replications, telomeres become critically short, which can lead to ‘genome instability’, and potentially
cancerous changes in our DNA. A short telomere acts as a signal for the cell to stop dividing, and to enter a
protective state called senescence.

Telomeres shorten naturally with normal aging, but they can shorten faster if we have unhealthy lifestyles, including
a poor diet. Therefore, telomere length may be used as an indicator of health, and disease risk.

TELOMERES AND AGEING

Mice models lacking the enzyme telomerase were found to show signs of premature ageing.

According to a research, short telomeres trigger age-related pathologies and shorter lifespans in mice and humans.

Mice with hyper-long telomeres show less metabolic aging and longer lifespans

However, it is not certain whether telomere shortening is responsible for ageing in humans or whether it is just a
sign of ageing, like grey hair.

Premature ageing can be reversed by reactivating an enzyme that protects the tips of chromosomes, a study in mice
suggests.

Mice engineered to lack the enzyme, called telomerase, become prematurely decrepit. But they bounced back to
health when the enzyme was replaced. The finding, published online today in Nature1, hints that some disorders
characterized by early ageing could be treated by boosting telomerase activity.

It also offers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it
has stopped working, says Ronald DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard
Medical School in Boston, Massachusetts, who led the new study. "This has implications for thinking about
telomerase as a serious anti-ageing intervention."

Other scientists, however, point out that mice lacking telomerase are a poor stand-in for the normal ageing process.
Moreover, ramping up telomerase in humans could potentially encourage the growth of tumours.

There are several indications that telomere length is a good predictor of lifespan.

Newborn babies tend to have telomeres ranging in length from around 8,000 to 13,000 base pairs. It has been
observed that this number tends to decline by around 20-40 base pairs each year. So, by the time someone is 40
years old they could have lost up to 1,600 base pairs from their telomeres.

However, looking at the bigger picture, the overall shortening of our telomeres is not significant, even in very old
people.

Cells that divide rapidly, such as germ cells and stem cells, are among the few cell types in our bodies containing
active telomerase.

This means that in these cells’ telomere length is maintained or even lengthened over time.
However, there are a number of other factors that have an effect on the length of our telomeres that all need to be
considered, such as smoking and obesity.

For the majority of our chromosomes, telomere length is finite and cannot be extended. Although it is within our
capabilities to limitlessly propagate telomeric DNA, the activity of the enzyme telomerase, which is responsible for
such extensions, is restricted to a small percentage of stem cell subtypes [7]. Consequently, the inevitable genetic
truncation that occurs during each round of replication is referred to as a ‘molecular clock’ that is a characteristic of
ageing: telomere length and age are negatively correlated.

We lose roughly 26.3 base pairs each year; as our DNA shortens, pro-ageing pathologies including DNA damage, cell
death via apoptosis, and carcinogenic transformation are promoted [8]. These outcomes can drive the emergence of
many ‘age-associated’