Is Ageing Inevitable? Understanding the Biology of Ageing | Open Lecture | University of Kent

Thank you for coming to this lecture. Today we’re going to talk about the biology of aging, right, which is a topic that myself
and some other researchers in the Bio- sciences Department at Kent as well as a whole community of
scientists worldwide are interested in, OK, and it’s something
that most most of you will also have a vested
interest in because you yourselves will age and you will know
lots of people at different ages And it doesn’t just, it’s not a process that only happens to
humans, it also happens in other species and here we have the honey bee. At the
center is the queen bee who lives for around about six years
whereas her workers only live for about six weeks so within this
one population that has exactly the same genetic background
is a huge discrepancy in the amount of time that an individual
can live for so what scientists are interested in, in bees and in other species, is trying
to find what it is, what are the differences between those that are living for a long
time and those that are not and trying to use these to understand
the aging process and perhaps trying to find ways that we can intervene in it. So back to humans now
for a moment. This is a picture of my son with his dad,
and his granddad, and his great granddad, and he was lucky
enough to meet his great granddad, which not everyone is, and this is because his great granddad lived till he was 96 but he lived a very happy and very healthy life, which is the most
important thing, at least in my opinion, and I think a propos here is an example
of how most people would like to age. They would like to be, they would like to
live as long as they are independent and healthy and happy, and that’s what we
try and do as aging researchers. We’re not
interested in just trying to indiscriminately make everyone live for
hundreds and hundreds of years in a decrepit state. What we want to do is we really want
to do away with this portion of ill life that a lot of elderly people suffer at the end of their lives and instead, you know, we want to improve the amount
of time that people are healthy during their life span, right and, as a result of that, there may well be a
number of years that are added to the end of life, OK, but hopefully most of these will be
healthy ones. And there are examples in nature that
make us think that this could be possible because they’re actually species that
don’t seem to age at all, and this is one of those, this is
a Freshwater Hydra, It’s really quite beautiful. You see it
floating around in the water. Tiny little thing, but if scientists isolate populations of this species from
the wild, which presumably would have a whole
range of different ages in them, and then they take these
populations into the lab, they don’t seem to age at all, and they, a few of them die, but really they seem
to go on for a very long time. OK, so there’s something about this process of aging that doesn’t mean that happens, has to happen So as well as this Hydra, scientists tend to study a range of other
different species and this is because aging studies in
humans tend to be very long and often quite expensive to do. So what scientists do is they use model
organisms so this can range from the baker’s yeast so this is the same yeast that’s used for
making bread and for brewing beer called Saccharomyces Cerevisiae, a very basic organism but we also use C. elegans, which is an nematode worm. The fruit fly, which can be found on any fruit bowl. This is Drosophila Melanogaster, and then you’ve got the mouse, Mus Musculus. And there are a number of advantages to using these organisms and one of the main ones is that we
know their whole genome. Their genomes have all been sequenced,
right, so we can do really good genetics on them, and the populations of each one of
these is homogeneous, right, which again, when you’re dealing with
humans, there’s much more variety to contend with. Much faster to do aging experiments in
these organisms, so for example a worm will only
live for three weeks, the fly for about three months, it also make these experiments a lot
cheaper to do in the lab. But the important thing to remember is
that all of the species, what we learn in these species, can be related to humans because lots of the genes and
lots of the pathways that scientists studying are the same in these organisms as they are in humans.
So I’m going to give you one example now from my own research and this is the nematode worm, Caenorhabditis elegans,
or C. elegans for short and here you can see it crawling
around, this is a picture from the lab, and it crawls
around in bacteria, that’s what it grows on. In the wild you
can find it in compost, composting fruit, but in the lab we grow it on small agar plates which have been
seeded with a little bit of E-coli bacteria. The worms crawl around
in that quite happily. The biggest one that you can see here in
the middle is an adult and it’s now producing eggs, and it’s a
hermaphrodite so it produces both the eggs and the sperm which self-fertilize to go on to produce embryos. And during its lifetime its going to lay around about 300 embryos over about five days, OK, so you get a lot of
worms very fast. And then these eggs, they’re laid onto the
plate and they hatch and they develop through four larval stages until they become adults themselves
again and start the reproductive cycle all over. There are round about 20,000 protein-coding genes in the worm, so
this means the genes that we know what protein is incubating code for, and these have been mapped to a lot of different pathways which a
conserved through from worms all the way up to mammals in a
lot of cases. These animals only live for three weeks so I can do an experiment in the lab in
under a month in an effort to find out the effect of
something on aging and they come with a really good tool kit, especially for genetics. It’s possible to
knock out genes in this worm, and it’s possible to increase the
expression of genes in these worms so you can actually look at the
detailed function of individual individual genes. And of these 20,000 protein-coding genes that it has,
about 75 percent of them a similar to genes that found in
humans. So they live for about three weeks but after the reproductive part of their
life is over, so that first five days of adulthood, what happens to them. Well, the kinda crawl around on the plate a bit,
they start to slow down and if you start to look at them really
carefully you can actually look at lots of markers of aging and some of these are muscle degeneration, or fat
accumulating in their body wall muscle. Their skin gets a bit thicker. You can see that their food, the bacteria,
starts to clog up their gut and slow down their digestive
system. Their neurons branch, and they form tumors in their uterus and also you have some accumulation of yolk from the embryos in the
intestine as well. So let’s have a look at the video and on the left we have a young worm you can see, it’s crawling around the plate
really happily and on the on the right is an old worm, so when you
prod it with the worm pick, that’s what we call the tool that we scientists use to manipulate these animals, if you prod it, it barely moves at all.
It actually looks a bit dead in this picture but I can assure you that it’s
not, it’s alive, I looked at it very carefully and
the microscope. But this just gives you an idea of what
we’re looking at. But what we do, is we generate life span
data so we generate life span curves, as we call them, right, So we start with a population of around
about 100 worms on a plate, and every day, or every two or three
days, we look at them and we determine whether each one is
dead or alive by poking it with that worm pick, and that’s what each point on this
graph is. So every day we figure out the
percentage of worms that is alive. So for quite a long time at the beginning,
everybody’s alive in that population, nobody dies, but then at some point in
the middle starts to drop off pretty fast, so WT stands for wild-type which is a normal
worm. So this is the normal worm’s life
span, on average around about three weeks, OK, but then what we do is because we’re
trying to understand the genes that are involved in this process,
is we start playing around with the worm’s genome, and we start making genetic mutations OK, and
this is a repeat of an experiment that was done by
Cynthia Kenyon in the early nineties which really kick-started the aging
fields, particularly in C. elegans. And what she did, was she made a point mutation in the gene called Daf-2 and she found that with the worms that carried this one
mutation, so this is one tiny change their genome, lived for twice
as long as those that were pretty much normal, that didn’t have this mutation. And she
found that also if you combine this mutation
with another one, called Daf-16, this effect went away, and myself
and others are extremely interested in trying to
understand what it is about this genetic mutation and about
this one here that relates to it that is actually
responsible for this effect on life span. And one of the reasons for this is that
this gene, this Daf-2 gene, is actually the worm
equivalent of the human insulin receptor so it’s its conserved, it’s the same. There
is an equivalent of Daf-2 in flies and in mice and also in humans, and this one
gene, which is a receptor gene, is at the top
of a pathway at the top of a signalling pathway, and the details of this are not important at the moment, this is something that you will learn about as you go through your undergraduate degree at Kent, but these pathways are conserved throughout the
species. So what we learn in the worms about
the role of this pathway in life span can also be applied to the flies, to
the mice and ultimately also to humans. And another really impressive thing about these long-lived worms, so these worms with this one genetic mutation in the Daf-2 gene, is that not only are they living twice
as long, but they’re also incredibly healthy. They’re moving really happily around the plate for a really long time into their life span, much longer than
a normal worm. So they don’t seem to be suffering
from the muscle degeneration, something that could be related to human
Sarcopenia, and they’re not suffering from the accumulation of
lipids in their body wall muscles, they’re not getting as many tumours in in their uterus, and their neurons aren’t branching as much. And we can relate all of these
things, or we can try to relate these things to the human aging condition. So what we’re doing,
going back to the earlier point, is that what we’re trying to do is not have this portion of ill health at the end
of life, but not only extend life span and also increase the amount of time
that an individual is healthy for. Thank you very much for your attention.