Telomeres explained: role in genomic stability, stem cells, replicative senescence | Elissa Epel
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Telomeres explained: role in genomic stability, stem cells, replicative senescence | Elissa Epel

– [Rhonda]: You mentioned telomeres a few
times. So for people listening or viewing that aren’t
quite familiar with telomere biology, maybe you can give a quick just, you know, background
on what telomeres are, and why they are involved in the aging process, why they’re biomarkers
for aging? – [Elissa]: Sure. So people like to think of them as like the
aglets of the tips of shoelaces, this plastic caps to keep shoelaces from fraying. So when you think of our linear chromosomes,
they’re all capped at the end with this wound up strings of DNA, repeating DNA called telomeres. And they are protecting the genome from damage. So they’re very important that way. They are sensing chemical signals of stress
in the cell. And so if there becomes a toxic situation,
they think the cells in danger, they are going to… well, that cell can shut down to protect
the body. But also the telomeres get worn down very
quickly when there’s a lot of stress. And so stress biology and aging biology are
actually really tied up intimately. – [Rhonda]: They take the hit, so they’re
trying to protect your DNA from potentially acquiring a mutation that could lead to something
like cancer. – [Elissa]: Yes. – [Rhonda]: So they sort of take the hit for
the cell? – [Elissa]: Right. – Rhonda]: In your experience, how much would
you say that telomere length…so, you know, the telomeres get shorter with time and shorter
telomeres are supposed to correspond to aging. How much would you say that telomere length
regulates the aging process, like actually plays an active role, versus just is a biomarker,
something that is just biomarking the aging process? – [Elissa]: That’s a good question. So telomeres are one specific pathway of how
a cell ages, and how our tissue ages. And the pathway is this, it’s called replicative
senescence and it’s basically how long can that cell continue to divide, and divide,
and replenish into new fresh young cells. So the telomeres, when they get too short,
prevent that particular cell, whether it’s an immune cell or a neuron in our hippocampus
or the lining of our cardiovascular system, we need those cells to replenish throughout
the decades. When it to the telomeres gets too short that
cell stops dividing. And so it’s basically a little window into
how long can these cells continue dividing. If the telomeres are long, they have a long
potential for replenishing tissue. – [Rhonda]: So it sounds like the telomeres
are much more important in stem cell populations, populations that are really responsible for
replenishing a variety of cell type including tissue. – [Elissa]: Right, absolutely. – [Rhonda]: You know, would you say that there’s
a difference between how telomeres shorten or, you know, what the attrition rate of telomeres
and stem cells are versus other cell types that are non-stem cells? – [Elissa]: Yes. So if we could measure stem cells more easily,
we would realize that partly what we’re measuring in any tissue is the health and longevity
in telomere length of the stem cell. So the stem cells lead to progenitor cells. And then there’s all the offspring. And so when we look at blood, we’re looking
at the offspring in the different circulating cells that roughly reflect the health of the
stem cell. – [Rhonda]: And there’s a variety of different…so
you’re talking about the damage that happens with age and how that can accelerate telomere
shortening because they sort of take the hit, they’re protecting our DNA. There’s an enzyme that can rebuild telomeres
right? – [Elissa]: Right. – [Rhonda]: Talk a little bit about that enzyme,
but it’s not active in every cell, correct? – [Elissa]: Right. So the telomerase enzyme is a very interesting
enzyme that is intracellular, that it has the ability to actually rebuild telomeres
by adding back base pairs. So it’s an RNA reverse transcriptase. And this was discovered by Liz Blackburn and
Carol Greider and colleagues, you know, over 25 years ago. And they were showing how if you knock it
down, the cells cannot divide anymore. And if you upregulate it, the cells become
immortal. So it is an important regulator of how long
a cell can divide. It’s one of the major determinants of telomere
length because if your telomere is shortening and you have a lot of telomerase, you can
repair them, you may be even can lengthen them. – [Rhonda]: And telomerase, if I remember
correctly, it’s more active in stem cells than in somatic cells, for the most part? – [Elissa]: Yeah, so at UCSF, my colleagues,
Jue Lin actually has an essay. It’s very sensitive and can measure the level
of telomerase in our normal blood cells. They’re not cancerous, they’re not stem cells,
but you can still measure the level. And that is associated with health, with metabolic
health, with social economic circumstances.

3 thoughts on “Telomeres explained: role in genomic stability, stem cells, replicative senescence | Elissa Epel

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