- [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.