November 13, 2023 • 35 mins
Thanks to technology and the convenience of our modern lifestyle, we are far less active today than previous generations. But how have our bodies adjusted to that massive physical slow-down? In this episode, we speak with endocrinologist and clinical scientist Professor Katherine Samaras, who is working every day to improve lives.
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Episode Transcript
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Dr Viviane Richter (00:01):
Three hundred years ago, our lives were very different. We had
labouring jobs. There were no screens to keep us on
the couch. But today we are much less active and
more than half of us live what you'd call a
sedentary lifestyle. So how have our bodies adjusted to that
massive physical slowdown? Today we meet a researcher who is
(00:24):
an expert in metabolism and is working every day to
improve lives. You're listening to Medical Minds. The podcast that
takes you inside the labs at the Garvan Institute of
Medical Research. I'm your host, Dr Viviane Richter. And with
me here is Professor Katherine Samaras, head of the Clinical Obesity,
Nutrition and Adipose Biology Lab at Garvan and Endocrinologist at
(00:47):
St Vincent's Hospital Sydney. Welcome, Katherine.
Prof Katherine Samaras (00:50):
Thank you Viviane. It's great to be here.
Dr Viviane Richter (00:52):
Katherine. I heard your love for science didn't start at
school or university, but in your dad's back shed. Is
that right? Can you tell us about that?
Prof Katherine Samaras (01:03):
Viviane, you're absolutely right. So picture this. The late 1970s,
suburban backyard. Everybody has one of these garden sheds. It's
the repository of all of the school projects that Mum
won't throw away, all the tools are in there and
there's a great big bench and the radio's on. There's,
you know, the rockstars of the late seventies playing. And
(01:25):
then we've got the rockstars of science there as well.
Marie Curie is there. Alexander Fleming, Louis Pasteur. You know,
I think of 4th class school projects in science. And
so I had set up this little lab in the
back shed, and I had been given a microscope at
some point as a Christmas present. And so everything was
underneath there, and we were mixing. It was a mortar
(01:48):
and pestle, and we were mixing all sorts of things
that we found in the backyard, smashing them to bits,
seeing what they were made of, looking under the microscope
and seeing what the structure of various things were. It
wasn't a great microscope. I've used much better since, but
it was the start and filtered in there along with
(02:08):
stories of spies and adventures and pirate stories. Was this
sort of fantasy around science and the world contained within it.
Dr Viviane Richter (02:18):
So these rockstars of science
You were inspired by them?
Prof Katherine Samaras (02:23):
Oh it was through school. Um school projects. And then we
were allowed to, you know, pick one of these scientists.
So there was Marie Curie. She was the only woman
that they presented. So the whole notion of how science
is really about cooking you start with an experiment and
it takes you somewhere. But sometimes that experiment doesn't go
(02:44):
to plan like in her situation and that leading to
discovery in the same way that Alexander Fleming – his discovery
of penicillin, th at was a fortuitous accident as well. And
that whole how fortune plays a role in science. There's
so much that's well thought through. And then there's a
little bit of fortune. There's a little bit of, um, serendipity,
(03:06):
and there's a little bit of pure luck. And then
there's pure accident. And I love that there's that spontaneity
in science.
Dr Viviane Richter (03:15):
Did you realise you wanted to be a scientist one day?
Prof Katherine Samaras (03:18):
Look, I probably was much more inspired by 99 in
Get Smart. So that's really showing my age. But, um,
you know, I thought she had a fantastic life. I
liked the sports car. I liked her spy lifestyle, the travel,
you know, who didn't like Smart himself. Um, there So
(03:38):
there was all of this other fantasy going on at
the same time, there was the science, and that was
really fascinating. But then there was adventure and other stories. So,
you know, I probably thought, oh spy, the spy life
is for me. Which, of course – I'm a very conservative person –
not at all. But it was science that really caught
my attention in the longer term. And then there were
(04:00):
many more opportunities. As one progresses through schooling to find
science and explore science and really start to understand the
the universes that are contained within it.
Dr Viviane Richter (04:13):
This idea of putting things under the microscope studying things
in great detail is this what led you to your
career as a clinician researcher, in a way?
Prof Katherine Samaras (04:24):
I think definitely. I've always been fascinated by how do
things work. How do they not work? Because most human
disease is where things don't work properly, so understanding what can
go awry, what pathways can take you one way versus
another way. What is fascinating about the human body is
how we have our genes. And we think that that
(04:46):
is like a blueprint. So much can change after that,
we know about epigenetics and how we can modify through
environmental influences the way our genes show themselves. So even
when you have the blueprint, there is so much potential, for
malleability and change, and to change the trajectory and course
of what we think of as a set course. And
(05:09):
these are lessons for life, really. They're things that inspire
me in every way in understanding what happens to disease.
And how can I actually change this person's pathway so
that they have better quality of life and better health
in the longer term?
Dr Viviane Richter (05:26):
Can you tell us what an endocrinologist does?
Prof Katherine Samaras (05:29):
An endocrinologist is a hormone doctor. Now, when we talk hormones,
people think about ovarian hormones. They think about testosterone, they
think about the thyroid. But there are so many other hormones,
and the major hormone in endocrinology is insulin, and insulin
obviously looks after glucose regulation. But it has other effects
(05:49):
on cell ageing, cell proliferation and cancer, aspects of building muscle.
So I see people who have common conditions like diabetes
and thyroid disease, osteoporosis, adrenal conditions, pituitary conditions. I look
after thyroid cancer patients, so some of the pituitary tumours,
(06:12):
the adrenal tumours, the thyroid tumours. They can be cancerous
tumours or they can be benign. So I look after
their care and some of these conditions can be fixed.
And so many of these conditions are long term conditions
where I walk a pathway with patients for decades.
Dr Viviane Richter (06:29):
That sounds extremely busy. Can you tell us what is
involved in your day to day?
Prof Katherine Samaras (06:34):
I sometimes joke that one should have a number of clones.
I'd like six clones, so I could then do things
as fully as I possibly could. There is the patient
side of life, and that intrudes 24/7. I have my
set clinics, and for those you have to be in
the zone. It's me and one person, and I'm trying
(06:56):
to understand how I can improve their quality of life
and change what their likelihood is going to be of
having a disease, experiencing a disease, changing that process and
that can run from 7:30 in the morning till 7:30
at night, sometimes later. Then I put my research hat on,
(07:17):
and that's my protected time in the laboratory. And there
I run studies. We do work that involves people's samples, um,
human samples and that can be tissue. It can be blood.
We are doing a study at the moment that is
looking at the brain and brain metabolism and brain health.
And so that involves a very specialised magnetic resonance imaging
(07:38):
of the brain to look at not only structure but
look at function of the brain, the connectivity of one
neuron to another. It's just so fascinating what technology allows
us to do. The study involves an intervention. It involves
giving the medication metformin to prevent brain ageing. So it's
the nuts and bolts of how the drug works, ow
(08:00):
does it interact with this particular participant? Is this person
experiencing any side effects? And so that has its humanistic element.
It also has quite a lot of due diligence and paperwork,
so we have to make sure everything is done correctly
in a clinical trial. There are the ethics that need
to be continuously thought about, and are we meeting our
(08:22):
ethical obligations and we take those things very, very seriously.
So there are aspects to this that are really quite important.
Dr Viviane Richter (08:31):
So you work with patients every week. What are the
implications of these conditions that people are coming to you with.
Prof Katherine Samaras (08:38):
If we talk about obesity and diabetes, common conditions that
I treat, both of those have consequences long term. For example,
obesity is probably the most common cause of cancer in
Australia today. Diabetes is the most common cause of kidney failure,
renal transplantation and dialysis in Australia. It's the commonest cause
of blindness. Its a very common cause of amputation. And
(09:02):
all of these conditions can be prevented if you get
in early and even prevent diabetes, or at least achieve
remission or excellent control of diabetes. And you can avoid
all these devastating consequences. One of my inspirations was seeing
a man in his sixties who had diabetes, and he
(09:23):
had a festering diabetic ulcer on his foot. It couldn't
have been cured with months of antibiotics and surgeries, and
he needed a below-knee amputation and seeing the impact of
the amputation on him, his mobility, his independence, his struggle
afterwards to deal with a prosthesis and to regain his
(09:44):
independence taught me how important it was to try and
prevent diabetes getting to that stage. And it can be done:
early intervention for prevention as well as when people actually
have these conditions to give them the best possible care.
Dr Viviane Richter (10:00):
Do we know enough about these conditions to prevent them
at this point?
Prof Katherine Samaras (10:05):
So one of the things I've been fascinated about is
how weight management can actually turn around prediabetes to normal
glucose metabolism and even diabetes back to prediabetes or normal
glucose metabolism. So addressing the obesity is a very big
factor in changing the course of diabetes. Not all people
(10:29):
with diabetes are obese. Many people are lean. They have –
there are multiple forms of diabetes. One form is brought
on by obesity. Other forms are clearly genetic, and people
can have diabetes when they are even very lean. However,
a good proportion of the people that we see day
to day have got weight issues, and a 5kg weight reduction
(10:52):
can make such a difference to their diabetes, not only
the markers that we use to know that we're being
successful in our treatment. Blood glucose control, blood cholesterol control,
making sure blood pressure is right, making sure physical exercise
is there, ensuring the quality of the diet. We can
make sure that those things are fine, but to really
(11:14):
change it and get that weight off and keep it
off for the long term makes such a difference. And
that has economic benefit for governments as well. It costs less
when people don't have their heart attack. It costs less
if people can stay in the workforce and participate at
a productive, meaningful level economically, socially, but also for people's
(11:36):
mental health. So there are broad brush benefits from nabbing
a condition like diabetes, especially really early.
Dr Viviane Richter (11:45):
So from your research, what have you discovered about how
we can better prevent diabetes and these terrible associated impacts?
Prof Katherine Samaras (11:55):
So getting in early with obesity management is important being
effective in obesity management, whether that's with medications or with surgery,
if necessary, if lifestyle changes haven't helped people. Getting in
there early with the right kinds of medications. And so
one of my big research interests is metformin. Metformin is
(12:21):
derived from French lilac, the flower. It's been around for
70 years, so it has an incredibly robust safety profile.
We give it to pregnant women, when they have gestational diabetes.
We give it to young women and children who have
got polycystic ovary syndrome. We use it to treat overweight
children with really long term safety data.
Dr Viviane Richter (12:43):
So metabolism is closely linked to many other functions in
the body. How does that work?
Prof Katherine Samaras (12:49):
All cells rely upon energy just like a car. If
you don't have petrol in the tank, the car is
not going to go. All of our cells require fuels,
and the predominant fuel is glucose, and the predominant fuel
needs insulin to work. Fatty acid is a very important
fuel as well. And within all of our cells, the
(13:13):
mitochondria are like the powerhouses that make sure all cell
functions happen and for that, body needs glucose, and it
requires fatty acids. So these two fuels are the things
that actually make our cells work. But an imbalance in
these fuels actually leads to cellular dysfunction and can lead
(13:34):
to cell death as well. And one of the really
interesting things about obesity is how nutrient toxicity actually starts
to operate. So if cells are overwhelmed with energy supply,
the nutrients start to cause toxicity, and this occurs in
different subcellular parts of our cells. The mitochondria, for example,
(13:55):
the endoplasmic reticulum, the sort of the structural parts of
our cells. I don't know how much the audience remembers
of their biology lessons. These little parts of the machine
of every cell require good fuel. And just like any
engine to operate and run smoothly, it needs the right
balance of fuel.
Dr Viviane Richter (14:15):
So these imbalances in metabolism that you're talking about, the
changes that you see, they lead to long term impacts?
Prof Katherine Samaras (14:23):
And you can see these rather quickly. So, for example,
if a cell is overwhelmed with carbohydrate molecules, there are
special receptors on the cells that actually can turn on
inflammation in a huge way through our immune system, but
also through cells secreting hormones that are called adipokines, some
(14:45):
of which actively promote cell inflammation. And when you have
cell inflammation, it's like a war zone. There is death
and destruction and premature ageing of cells. And so if
we look at various ageing processes, inflammation is implicated very
heavily in these. If we look at atherosclerosis, the hardening
(15:07):
of arteries inflammation plays a very prominent part there as well.
If we look at brain ageing, inflammation is implicated in
the development of dementia. Obesity drives that because it's an
excess of nutrient, and it's acting at those cells to
start that inflammatory process and the wearing out of our cells,
(15:30):
so you basically then start to lose cells, and that's
when you start to get cell drop out. Now, cell
dropout occurs and you lose function when you start losing function.
That's where you start to see the pancreas fail and
diabetes developing. It's where one might see the heart starting
to fail. It's when the brain function starts to fail,
(15:50):
and that's when you start to see cognitive impairment, cognitive
decline and eventually, dementia. So those metabolic processes play a
role in every single pathway we have in the body.
Dr Viviane Richter (16:02):
And that's where your research comes in, because you're looking
at a way to potentially prevent or slow down dementia
from developing.
Prof Katherine Samaras (16:11):
That's right, Viviane. We're trying to slow down cognitive decline
in people who have got a mild cognitive impairment already,
repurposing a medication called metformin that we talked about, the
medication that can prevent diabetes and is first line to
treat diabetes. And what we found in the Sydney Memory
and Ageing Study was that people with diabetes on this
(16:34):
medication had much lower rates of dementia. Now diabetes, doubles
or triples, the risk of developing dementia and what we
observed was that people had almost 80% lower rates of
dementia if they were on metformin for their diabetes compared
to people who were not. And it was not related
to the severity of diabetes. Some of these people were
(16:54):
just diet controlled and had really good diabetes control, but
they weren't on metformin. So we're exploring how metformin, acting
through metabolic and inflammatory pathways, can actually turn down that
brain ageing process and halt cognitive decline and try and
prevent its relentless progression to more moderate and extreme cognitive impairment.
Dr Viviane Richter (17:20):
Through your MetMemory study, what are you hoping to achieve?
Prof Katherine Samaras (17:24):
We're hoping that metformin slows down brain ageing in people
who already have mild cognitive impairment. If we can do that,
we will have a super safe therapy that is available
for prescribing today.
Dr Viviane Richter (17:39):
How has our metabolism evolved over time?
Prof Katherine Samaras (17:43):
So don't forget we started as hunter gatherers. We wouldn't
have thought twice about crossing a range of mountains to
hunt for food. We would have had seasonal access to food,
and there would have been periods of seasonal privation. The
crops failed. Perhaps there was a war or a blockade,
and we didn't have access for maybe a year or
two to the amount of food we generally had access to.
(18:06):
We were very much involved with the cycles of the earth,
the spring, winter season, and there would be times where
there would be food, summer, autumn and then times where
there was nothing. And so our body has evolved over
millennia so that we can serve energy when we find it.
And so we are fantastic banks for fat and energy
(18:29):
if we access it and we've been kept safe because
of just the natures of cycle and life and our
work and our environment. But now if you shift forward,
we find ourselves in places where we just press buttons
and the whole of our food can appear. We didn't
sweat a single bead of sweat, but we're also used
(18:52):
to seeing these huge plates of food. And on those
plates are energy-dense food and the energy-dense foods are actually
really cheap these days, and so processing of food, the
presentation of small morsels of very energy-dense food The capacity
of human beings, our wiring is to eat everything in
(19:13):
front of us. It's not because of what Grandma went through
in the war, it's actually we are wired that when
we see food, we secrete hormones that make us seek
and destroy all of it that is in front of us,
and that is human nature. Everybody does this. We are wired.
We don't even have to swallow the food before hormones
are being secreted to store the energy. So we are
(19:35):
magnificent energy storage machines, and we now have ready access
to cheap energy-dense foods. And so, of course, we eat.
We've been encouraged to snack, we've been encouraged to graze,
and there are market forces that are involved in that.
But it leads to energy over-consumption, and on the other hand,
(19:57):
we're not moving. So the energy balance is very much
in the favour of storage, storage, storage and hold on
to that energy. Because maybe there's a famine coming. They're
our genes. And then the environment is providing so much
energy with very little opportunity to expend any energy. How
many people are trapped in the car for an hour
or up to two hours per day, commuting to their workplace,
(20:19):
where they might be chained to a desk for eight hours?
We barely move our the only thing that moves are
our fingers on the keyboard and our mouths on Zoom meetings.
Dr Viviane Richter (20:29):
So what do you think is the answer to somebody
listening to this? Who might think? Well, that's me. I'm
stuck in Zoom meetings all day. I'm stuck in the car.
Prof Katherine Samaras (20:38):
So there are lots of things we can try and do.
The first is contain our food intake or make our
plates smaller, not have visual triggers or stimuli. Where we're
getting food impulse signals all the time. We have to
make our lives more physically inefficient. Let's move the printer
so that we have to walk some distance to pick
something up off the printer. How about making steps? Why
(21:01):
don't we accrue our steps? Everybody has monitors. Are we
getting 10,000 steps per day? What am I doing for
my fun? Why am I just sitting or watching some
stuff on TV or at the computer? Why aren't I
out doing something? Why aren't I playing sport with my friends?
Why aren't I going for walks with my friends? Why
am I going to restaurants constantly and just sitting for
(21:22):
more time of the day? Maybe we can cook together.
Maybe we can go on a picnic.
Dr Viviane Richter (21:28):
So is it just lifestyle? Is that all we have to change?
Prof Katherine Samaras (21:32):
So lifestyle is the bit that we can change the
bit that we can't change is our genetic predisposition. We
just know by looking at our parents and our grandparents,
whether we have those genes for magnificent energy conservation in
a small dose or a very, very big dose, and
so we can prevent by being proactive and preventing ourselves
(21:55):
becoming sedentary, preventing ourselves carrying an extra couple of kilos
through lifestyle intervention. What's really fascinating is if you have
got genetic predisposition to be overweight, if you have genetic
predisposition to have type 2 diabetes that environmental factors can
epigenetically change how those genes manifest so that you can
(22:18):
prevent diabetes, for example, by being active. So everybody who's
got parents or grandparents with type 2 diabetes needs to be as
active as they possibly can. They also have to modify
their diet, knowing that if they eat like Mum and Dad,
they're going to end up like Mum and Dad. So
our future is there. We can see it by looking
at our parents, um, by our grandparents and using that
(22:40):
information we can individualise for our own self and go right.
That needs to be my pathway.
Dr Viviane Richter (22:45):
You mentioned epigenetically. What is that?
Prof Katherine Samaras (22:49):
Epigenetics is the science of how we can either turn
up our genetic inheritance or turn it down. So, for example,
if we look at some of the genes for cancer, BRCA,
for example, is a gene that causes breast and ovarian cancer.
But in many families, if you have the gene, you
(23:12):
don't get the condition. And so it can often skip
generations and appear in a granddaughter, whereas it's avoided the
mother or the father, and it's affected a grandparent or
a great grandparent. Why those genes are turned off is
that they get turned off epigenetically, and the science of
how you can do that is fascinating. We know diet
(23:35):
can affect epigenetic regulation of gene expression. We know exercise
has a big role, and that's been shown best for
people with diabetes. It was the Harvard doctors study that showed this.
If you have two brothers and their father had diabetes
and one is active and one is not active, the
one that's active doesn't get diabetes. The inactive one does.
Dr Viviane Richter (23:59):
Can we talk about what is happening at the cellular level,
you've studied epigenetics of fat cells. Can you tell me
about that research?
Prof Katherine Samaras (24:09):
This was research with one of the premier epigenetics in
the universe who we happen to also have at the
Garvan Institute Professor Susan Clark. With Sue's group of scientists
who are epigenetics. We were able to take fat from
people that were undertaking an uncomplicated surgery, who had diabetes,
(24:31):
did not have diabetes and who were overweight or not overweight.
And we were able to look at where our fat
cells actually come from and what the sequence in the
development of that fat cell was going to be. So,
for example, what we found was that the cells that
become our belly fat and people understand belly fat as
(24:52):
the apple shape, carrying that extra fat in the waistline,
they are different to the type of fat cells you
find elsewhere in the body, and that embryologically the genes
that are regulated start to change at the embryonic level.
So from the time we are in the womb, fat
(25:14):
stores are being started to be regulated and set on
a certain path. Now, other work we know from maternal
nutrition during pregnancy is that if women are obese at
the beginning of their pregnancy, or if they gain a
stack of weight during their pregnancy, by which I mean
(25:36):
like 20+ kilos, that the baby will be born overweight
and at five years it's on a trajectory for being
an overweight child, so very much in the maternal environment,
you can actually set the genes for the embryo and
what's going to happen when it's born and what's going
(25:58):
to happen when it's five years old. So this is
an example of maternal nutrition affecting the offspring that is
epigenetic modulated, so you can have certain genes for obesity.
But then, if those genes are exposed to environments of
super nutrition, then you magnify the genetic effect
Dr Viviane Richter (26:22):
With the work that you're doing with all this research,
do you think we'll all live to 100?
Prof Katherine Samaras (26:28):
Many of us are actually reaching 100 now. There are
about 5500 centenarians living in Australia currently, and it's fascinating
to think about how they got there. What were the
conditions that they lived in? Obviously, they lived during the
war they lived during a depression. They've lived through times
of privation. They've also survived the periods of excess that
(26:52):
we've had in the last 50 years. I think it
is possible for people to live a long life with
their faculties intact, meaning perfect brain health. Their cognition is sharp.
They are wise, good heart health. They can walk. They
can exercise, normal metabolism and be free of cancer. Because
(27:13):
we have examples of that all the time. Nutrition plays
a huge role in getting there. And if we look
at the data that we have, and that's admittedly from
observational studies, we know that the Mediterranean-style diet is associated
with longer life. And if we break down the nuts
(27:33):
and bolts of the Mediterranean diet, it's getting our fatty
acids from things like olive oil and from fish and
limited meat. It's getting plenty of fresh vegetables every day.
Notice I didn't say fruit, fruit is full of sugar,
and it's important we get some fruit, but not a
(27:55):
lot of fruit. Every single day. It's important we look
at the Mediterranean lifestyle that physical activity has played a
very large part of those activities, and I'm not suggesting
that we become hunter gatherers, though some people choose to,
and that's wonderful. But we have to break down the
sedentariness of our current lifestyle and be more active in
(28:17):
different ways. We can also learn from the data on fasting.
There's really great data that people who fast, regularly and
for religious reasons live a lot longer. And that's when
you even control for things like smoking and alcohol consumption.
So these are not just people who are fasting. These
(28:37):
are people who also smoke and drink and do a
whole range of other things. But periodic fasting actually upregulates.
We know from cellular experiments and small animal experiments worms,
rodents that you periodically calorie restrict or fast animals. They
will live a lot longer, and the way that that
works is it upregulates all of our antioxidant production. So
(29:01):
at a genetic level, we respond to that caloric restriction
by upping the gene expression of genes involved in mopping
up radicals, free radicals and oxidative stress products that actually
cause inflammation and erode our body systems. So the fasting
side is fascinating as well as we start to scientifically
understand how that operates. I think the other factor with longevity,
(29:26):
and it's really important, is the cognitive side, because if
you get to 100 you want a body that works perfectly.
But you also want the brain that can drive the
body around to do all the things you want to do,
and understanding mental health is really important. One of the
challenges that older people have is loneliness and the way
(29:46):
that social isolation plays in to cognitive decline. That's really important.
Simple things like being able to hear properly, plays into
cognitive decline. If you don't hear you become increasingly socially isolated,
you don't pick up on cues in the environment, and
people start to actually have more accelerated cognitive decline associated
(30:07):
with that. The time-restricted eating has recently been shown to
be very beneficial for people who are trying to lose weight.
What's interesting in all of this is how our circadian
rhythms fit into that time restricted eating pattern. Because we
at a hormonal level sync with the daylight phase. We
(30:28):
actually do our eating during the daylight, and our metabolism
works best. If we eat during daylight hours. We're not
meant to eat through the dark phase, and so when
you think about the hormones that are involved in these
circadian rhythm. It involves hormones like cortisol for insulin. Our
insulin sensitivity changes through the day according to the light
(30:51):
and dark phase. So much of our food storage works
best if we eat during daylight hours.
Dr Viviane Richter (30:59):
So, Katherine, what motivates you in your research?
Prof Katherine Samaras (31:02):
My patients do, so I see what happens to them.
I want to understand better what the mechanisms of disease are,
and I want to be able to offer them better
solutions than what we have currently. I also think our
patients show us the natural history of a condition, and
(31:23):
we can learn so much from an individual's experience. One
of the privileges of being a clinician researcher is that
I get to see what's happening in the hospital in
the consulting room, and I can take that to the lab,
and that is a fundamental part, I think, of breaking
down the conditions that we treat and really understanding and
(31:46):
then being able to translate that back to a meaningful
intervention in the clinic. So that's what I love about
the research that I do, and it's what inspires me
to keep writing grants in the middle of the night
and reviewing papers in the middle of the night and
doing the stuff that actually is what makes up the
research and makes the research productive and and fruitful. So,
(32:10):
you know, that's what drives me. It's coming back to
the patient.
Dr Viviane Richter (32:15):
Katherine. Before we let you get back to the lab,
it's time for the Fast Five. What do you do
in your downtime?
Prof Katherine Samaras (32:22):
I garden. I grow vegetables. I'm an enthusiastic vegetable grower. I
would like to be self sufficient in some of our
vegetables if we possibly can. And then I pickle them
as well. I love fermented foods. It's so good for
the gut microbiome. So the prodigious, um, vegetables that manage
to grow in my garden get pickled if they're not
(32:43):
consumed immediately.
Favourite music. The Lark Ascending by Vaughan Williams. And I'll
tell you why. I find it absolutely peaceful and inspiring,
and it's basically a bird flying up into the summer sky.
And so it represents freedom. It represents the ability to soar,
(33:08):
and it's just the most beautiful, tranquil piece of music.
Dr Viviane Richter (33:12):
That's wonderful. Secret skills?
Prof Katherine Samaras (33:15):
Probably what I do in the garden. Um, give me
an axe. Give me a hoe. Yes. Big machinery, hand yielded,
of course. So you can chop down something. Give me
something to chop down.
Dr Viviane Richter (33:28):
You're hands on, Katherine!
Prof Katherine Samaras (33:30):
It's all that time in the shed.
Dr Viviane Richter (33:32):
What's the most challenging thing you've ever had to do?
Prof Katherine Samaras (33:35):
I do lots of challenging things. So it's hard to
say what the most challenging is. I can say what
challenges me. And that was being a young mum with
a screamer who I couldn't get to settle. My goodness,
the adrenaline was going in a way that it doesn't
when I you know, I'm managing somebody where you know,
(33:58):
their transplants failing, and they've had they've had a cardiac
arrest that doesn't raise my heartbeat. But a bad day
with children often did. I must say, um, so that
that challenged me... scarred me.
Dr Viviane Richter (34:14):
Um, kids are another level of challenge, aren't they?
Prof Katherine Samaras (34:17):
I hope my daughter never listens to this.
Dr Viviane Richter (34:20):
Fantastic. What's your dream holiday, Katherine?
Prof Katherine Samaras (34:24):
My dream holiday would be walking in the mountains somewhere.
High mountains. So the Alps in Switzerland, the Dolomites and
and just, you know, with a backpack and 12 hours
of daylight ahead.
Dr Viviane Richter (34:38):
Professor Katherine Samaras, Thank you so much for speaking with
us on Medical Minds today. It's been such a pleasure
having you.
Prof Katherine Samaras (34:46):
Viviane, it's been a privilege. Thank you.
Dr Viviane Richter (34:48):
If you'd like to know more about Katherine's research or
the work we do at Garvan, head over to garvan.org.au.
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter.
Thanks for listening.
This podcast was recorded on the traditional country of the
(35:09):
Gadigal people of the Eora Nation. We recognise their continuing
connection to land, waters and community. We pay our respects
to Aboriginal and Torres Strait Islander cultures and Elders past,
present and emerging.
Three hundred years ago, our lives were very different. We had
labouring jobs. There were no screens to keep us on
the couch. But today we are much less active and
more than half of us live what you'd call a
sedentary lifestyle. So how have our bodies adjusted to that
massive physical slowdown? Today we meet a researcher who is
(00:24):
an expert in metabolism and is working every day to
improve lives. You're listening to Medical Minds. The podcast that
takes you inside the labs at the Garvan Institute of
Medical Research. I'm your host, Dr Viviane Richter. And with
me here is Professor Katherine Samaras, head of the Clinical Obesity,
Nutrition and Adipose Biology Lab at Garvan and Endocrinologist at
(00:47):
St Vincent's Hospital Sydney. Welcome, Katherine.
Prof Katherine Samaras (00:50):
Thank you Viviane. It's great to be here.
Dr Viviane Richter (00:52):
Katherine. I heard your love for science didn't start at
school or university, but in your dad's back shed. Is
that right? Can you tell us about that?
Prof Katherine Samaras (01:03):
Viviane, you're absolutely right. So picture this. The late 1970s,
suburban backyard. Everybody has one of these garden sheds. It's
the repository of all of the school projects that Mum
won't throw away, all the tools are in there and
there's a great big bench and the radio's on. There's,
you know, the rockstars of the late seventies playing. And
(01:25):
then we've got the rockstars of science there as well.
Marie Curie is there. Alexander Fleming, Louis Pasteur. You know,
I think of 4th class school projects in science. And
so I had set up this little lab in the
back shed, and I had been given a microscope at
some point as a Christmas present. And so everything was
underneath there, and we were mixing. It was a mortar
(01:48):
and pestle, and we were mixing all sorts of things
that we found in the backyard, smashing them to bits,
seeing what they were made of, looking under the microscope
and seeing what the structure of various things were. It
wasn't a great microscope. I've used much better since, but
it was the start and filtered in there along with
(02:08):
stories of spies and adventures and pirate stories. Was this
sort of fantasy around science and the world contained within it.
Dr Viviane Richter (02:18):
So these rockstars of science
You were inspired by them?
Prof Katherine Samaras (02:23):
Oh it was through school. Um school projects. And then we
were allowed to, you know, pick one of these scientists.
So there was Marie Curie. She was the only woman
that they presented. So the whole notion of how science
is really about cooking you start with an experiment and
it takes you somewhere. But sometimes that experiment doesn't go
(02:44):
to plan like in her situation and that leading to
discovery in the same way that Alexander Fleming – his discovery
of penicillin, th at was a fortuitous accident as well. And
that whole how fortune plays a role in science. There's
so much that's well thought through. And then there's a
little bit of fortune. There's a little bit of, um, serendipity,
(03:06):
and there's a little bit of pure luck. And then
there's pure accident. And I love that there's that spontaneity
in science.
Dr Viviane Richter (03:15):
Did you realise you wanted to be a scientist one day?
Prof Katherine Samaras (03:18):
Look, I probably was much more inspired by 99 in
Get Smart. So that's really showing my age. But, um,
you know, I thought she had a fantastic life. I
liked the sports car. I liked her spy lifestyle, the travel,
you know, who didn't like Smart himself. Um, there So
(03:38):
there was all of this other fantasy going on at
the same time, there was the science, and that was
really fascinating. But then there was adventure and other stories. So,
you know, I probably thought, oh spy, the spy life
is for me. Which, of course – I'm a very conservative person –
not at all. But it was science that really caught
my attention in the longer term. And then there were
(04:00):
many more opportunities. As one progresses through schooling to find
science and explore science and really start to understand the
the universes that are contained within it.
Dr Viviane Richter (04:13):
This idea of putting things under the microscope studying things
in great detail is this what led you to your
career as a clinician researcher, in a way?
Prof Katherine Samaras (04:24):
I think definitely. I've always been fascinated by how do
things work. How do they not work? Because most human
disease is where things don't work properly, so understanding what can
go awry, what pathways can take you one way versus
another way. What is fascinating about the human body is
how we have our genes. And we think that that
(04:46):
is like a blueprint. So much can change after that,
we know about epigenetics and how we can modify through
environmental influences the way our genes show themselves. So even
when you have the blueprint, there is so much potential, for
malleability and change, and to change the trajectory and course
of what we think of as a set course. And
(05:09):
these are lessons for life, really. They're things that inspire
me in every way in understanding what happens to disease.
And how can I actually change this person's pathway so
that they have better quality of life and better health
in the longer term?
Dr Viviane Richter (05:26):
Can you tell us what an endocrinologist does?
Prof Katherine Samaras (05:29):
An endocrinologist is a hormone doctor. Now, when we talk hormones,
people think about ovarian hormones. They think about testosterone, they
think about the thyroid. But there are so many other hormones,
and the major hormone in endocrinology is insulin, and insulin
obviously looks after glucose regulation. But it has other effects
(05:49):
on cell ageing, cell proliferation and cancer, aspects of building muscle.
So I see people who have common conditions like diabetes
and thyroid disease, osteoporosis, adrenal conditions, pituitary conditions. I look
after thyroid cancer patients, so some of the pituitary tumours,
(06:12):
the adrenal tumours, the thyroid tumours. They can be cancerous
tumours or they can be benign. So I look after
their care and some of these conditions can be fixed.
And so many of these conditions are long term conditions
where I walk a pathway with patients for decades.
Dr Viviane Richter (06:29):
That sounds extremely busy. Can you tell us what is
involved in your day to day?
Prof Katherine Samaras (06:34):
I sometimes joke that one should have a number of clones.
I'd like six clones, so I could then do things
as fully as I possibly could. There is the patient
side of life, and that intrudes 24/7. I have my
set clinics, and for those you have to be in
the zone. It's me and one person, and I'm trying
(06:56):
to understand how I can improve their quality of life
and change what their likelihood is going to be of
having a disease, experiencing a disease, changing that process and
that can run from 7:30 in the morning till 7:30
at night, sometimes later. Then I put my research hat on,
(07:17):
and that's my protected time in the laboratory. And there
I run studies. We do work that involves people's samples, um,
human samples and that can be tissue. It can be blood.
We are doing a study at the moment that is
looking at the brain and brain metabolism and brain health.
And so that involves a very specialised magnetic resonance imaging
(07:38):
of the brain to look at not only structure but
look at function of the brain, the connectivity of one
neuron to another. It's just so fascinating what technology allows
us to do. The study involves an intervention. It involves
giving the medication metformin to prevent brain ageing. So it's
the nuts and bolts of how the drug works, ow
(08:00):
does it interact with this particular participant? Is this person
experiencing any side effects? And so that has its humanistic element.
It also has quite a lot of due diligence and paperwork,
so we have to make sure everything is done correctly
in a clinical trial. There are the ethics that need
to be continuously thought about, and are we meeting our
(08:22):
ethical obligations and we take those things very, very seriously.
So there are aspects to this that are really quite important.
Dr Viviane Richter (08:31):
So you work with patients every week. What are the
implications of these conditions that people are coming to you with.
Prof Katherine Samaras (08:38):
If we talk about obesity and diabetes, common conditions that
I treat, both of those have consequences long term. For example,
obesity is probably the most common cause of cancer in
Australia today. Diabetes is the most common cause of kidney failure,
renal transplantation and dialysis in Australia. It's the commonest cause
of blindness. Its a very common cause of amputation. And
(09:02):
all of these conditions can be prevented if you get
in early and even prevent diabetes, or at least achieve
remission or excellent control of diabetes. And you can avoid
all these devastating consequences. One of my inspirations was seeing
a man in his sixties who had diabetes, and he
(09:23):
had a festering diabetic ulcer on his foot. It couldn't
have been cured with months of antibiotics and surgeries, and
he needed a below-knee amputation and seeing the impact of
the amputation on him, his mobility, his independence, his struggle
afterwards to deal with a prosthesis and to regain his
(09:44):
independence taught me how important it was to try and
prevent diabetes getting to that stage. And it can be done:
early intervention for prevention as well as when people actually
have these conditions to give them the best possible care.
Dr Viviane Richter (10:00):
Do we know enough about these conditions to prevent them
at this point?
Prof Katherine Samaras (10:05):
So one of the things I've been fascinated about is
how weight management can actually turn around prediabetes to normal
glucose metabolism and even diabetes back to prediabetes or normal
glucose metabolism. So addressing the obesity is a very big
factor in changing the course of diabetes. Not all people
(10:29):
with diabetes are obese. Many people are lean. They have –
there are multiple forms of diabetes. One form is brought
on by obesity. Other forms are clearly genetic, and people
can have diabetes when they are even very lean. However,
a good proportion of the people that we see day
to day have got weight issues, and a 5kg weight reduction
(10:52):
can make such a difference to their diabetes, not only
the markers that we use to know that we're being
successful in our treatment. Blood glucose control, blood cholesterol control,
making sure blood pressure is right, making sure physical exercise
is there, ensuring the quality of the diet. We can
make sure that those things are fine, but to really
(11:14):
change it and get that weight off and keep it
off for the long term makes such a difference. And
that has economic benefit for governments as well. It costs less
when people don't have their heart attack. It costs less
if people can stay in the workforce and participate at
a productive, meaningful level economically, socially, but also for people's
(11:36):
mental health. So there are broad brush benefits from nabbing
a condition like diabetes, especially really early.
Dr Viviane Richter (11:45):
So from your research, what have you discovered about how
we can better prevent diabetes and these terrible associated impacts?
Prof Katherine Samaras (11:55):
So getting in early with obesity management is important being
effective in obesity management, whether that's with medications or with surgery,
if necessary, if lifestyle changes haven't helped people. Getting in
there early with the right kinds of medications. And so
one of my big research interests is metformin. Metformin is
(12:21):
derived from French lilac, the flower. It's been around for
70 years, so it has an incredibly robust safety profile.
We give it to pregnant women, when they have gestational diabetes.
We give it to young women and children who have
got polycystic ovary syndrome. We use it to treat overweight
children with really long term safety data.
Dr Viviane Richter (12:43):
So metabolism is closely linked to many other functions in
the body. How does that work?
Prof Katherine Samaras (12:49):
All cells rely upon energy just like a car. If
you don't have petrol in the tank, the car is
not going to go. All of our cells require fuels,
and the predominant fuel is glucose, and the predominant fuel
needs insulin to work. Fatty acid is a very important
fuel as well. And within all of our cells, the
(13:13):
mitochondria are like the powerhouses that make sure all cell
functions happen and for that, body needs glucose, and it
requires fatty acids. So these two fuels are the things
that actually make our cells work. But an imbalance in
these fuels actually leads to cellular dysfunction and can lead
(13:34):
to cell death as well. And one of the really
interesting things about obesity is how nutrient toxicity actually starts
to operate. So if cells are overwhelmed with energy supply,
the nutrients start to cause toxicity, and this occurs in
different subcellular parts of our cells. The mitochondria, for example,
(13:55):
the endoplasmic reticulum, the sort of the structural parts of
our cells. I don't know how much the audience remembers
of their biology lessons. These little parts of the machine
of every cell require good fuel. And just like any
engine to operate and run smoothly, it needs the right
balance of fuel.
Dr Viviane Richter (14:15):
So these imbalances in metabolism that you're talking about, the
changes that you see, they lead to long term impacts?
Prof Katherine Samaras (14:23):
And you can see these rather quickly. So, for example,
if a cell is overwhelmed with carbohydrate molecules, there are
special receptors on the cells that actually can turn on
inflammation in a huge way through our immune system, but
also through cells secreting hormones that are called adipokines, some
(14:45):
of which actively promote cell inflammation. And when you have
cell inflammation, it's like a war zone. There is death
and destruction and premature ageing of cells. And so if
we look at various ageing processes, inflammation is implicated very
heavily in these. If we look at atherosclerosis, the hardening
(15:07):
of arteries inflammation plays a very prominent part there as well.
If we look at brain ageing, inflammation is implicated in
the development of dementia. Obesity drives that because it's an
excess of nutrient, and it's acting at those cells to
start that inflammatory process and the wearing out of our cells,
(15:30):
so you basically then start to lose cells, and that's
when you start to get cell drop out. Now, cell
dropout occurs and you lose function when you start losing function.
That's where you start to see the pancreas fail and
diabetes developing. It's where one might see the heart starting
to fail. It's when the brain function starts to fail,
(15:50):
and that's when you start to see cognitive impairment, cognitive
decline and eventually, dementia. So those metabolic processes play a
role in every single pathway we have in the body.
Dr Viviane Richter (16:02):
And that's where your research comes in, because you're looking
at a way to potentially prevent or slow down dementia
from developing.
Prof Katherine Samaras (16:11):
That's right, Viviane. We're trying to slow down cognitive decline
in people who have got a mild cognitive impairment already,
repurposing a medication called metformin that we talked about, the
medication that can prevent diabetes and is first line to
treat diabetes. And what we found in the Sydney Memory
and Ageing Study was that people with diabetes on this
(16:34):
medication had much lower rates of dementia. Now diabetes, doubles
or triples, the risk of developing dementia and what we
observed was that people had almost 80% lower rates of
dementia if they were on metformin for their diabetes compared
to people who were not. And it was not related
to the severity of diabetes. Some of these people were
(16:54):
just diet controlled and had really good diabetes control, but
they weren't on metformin. So we're exploring how metformin, acting
through metabolic and inflammatory pathways, can actually turn down that
brain ageing process and halt cognitive decline and try and
prevent its relentless progression to more moderate and extreme cognitive impairment.
Dr Viviane Richter (17:20):
Through your MetMemory study, what are you hoping to achieve?
Prof Katherine Samaras (17:24):
We're hoping that metformin slows down brain ageing in people
who already have mild cognitive impairment. If we can do that,
we will have a super safe therapy that is available
for prescribing today.
Dr Viviane Richter (17:39):
How has our metabolism evolved over time?
Prof Katherine Samaras (17:43):
So don't forget we started as hunter gatherers. We wouldn't
have thought twice about crossing a range of mountains to
hunt for food. We would have had seasonal access to food,
and there would have been periods of seasonal privation. The
crops failed. Perhaps there was a war or a blockade,
and we didn't have access for maybe a year or
two to the amount of food we generally had access to.
(18:06):
We were very much involved with the cycles of the earth,
the spring, winter season, and there would be times where
there would be food, summer, autumn and then times where
there was nothing. And so our body has evolved over
millennia so that we can serve energy when we find it.
And so we are fantastic banks for fat and energy
(18:29):
if we access it and we've been kept safe because
of just the natures of cycle and life and our
work and our environment. But now if you shift forward,
we find ourselves in places where we just press buttons
and the whole of our food can appear. We didn't
sweat a single bead of sweat, but we're also used
(18:52):
to seeing these huge plates of food. And on those
plates are energy-dense food and the energy-dense foods are actually
really cheap these days, and so processing of food, the
presentation of small morsels of very energy-dense food The capacity
of human beings, our wiring is to eat everything in
(19:13):
front of us. It's not because of what Grandma went through
in the war, it's actually we are wired that when
we see food, we secrete hormones that make us seek
and destroy all of it that is in front of us,
and that is human nature. Everybody does this. We are wired.
We don't even have to swallow the food before hormones
are being secreted to store the energy. So we are
(19:35):
magnificent energy storage machines, and we now have ready access
to cheap energy-dense foods. And so, of course, we eat.
We've been encouraged to snack, we've been encouraged to graze,
and there are market forces that are involved in that.
But it leads to energy over-consumption, and on the other hand,
(19:57):
we're not moving. So the energy balance is very much
in the favour of storage, storage, storage and hold on
to that energy. Because maybe there's a famine coming. They're
our genes. And then the environment is providing so much
energy with very little opportunity to expend any energy. How
many people are trapped in the car for an hour
or up to two hours per day, commuting to their workplace,
(20:19):
where they might be chained to a desk for eight hours?
We barely move our the only thing that moves are
our fingers on the keyboard and our mouths on Zoom meetings.
Dr Viviane Richter (20:29):
So what do you think is the answer to somebody
listening to this? Who might think? Well, that's me. I'm
stuck in Zoom meetings all day. I'm stuck in the car.
Prof Katherine Samaras (20:38):
So there are lots of things we can try and do.
The first is contain our food intake or make our
plates smaller, not have visual triggers or stimuli. Where we're
getting food impulse signals all the time. We have to
make our lives more physically inefficient. Let's move the printer
so that we have to walk some distance to pick
something up off the printer. How about making steps? Why
(21:01):
don't we accrue our steps? Everybody has monitors. Are we
getting 10,000 steps per day? What am I doing for
my fun? Why am I just sitting or watching some
stuff on TV or at the computer? Why aren't I
out doing something? Why aren't I playing sport with my friends?
Why aren't I going for walks with my friends? Why
am I going to restaurants constantly and just sitting for
(21:22):
more time of the day? Maybe we can cook together.
Maybe we can go on a picnic.
Dr Viviane Richter (21:28):
So is it just lifestyle? Is that all we have to change?
Prof Katherine Samaras (21:32):
So lifestyle is the bit that we can change the
bit that we can't change is our genetic predisposition. We
just know by looking at our parents and our grandparents,
whether we have those genes for magnificent energy conservation in
a small dose or a very, very big dose, and
so we can prevent by being proactive and preventing ourselves
(21:55):
becoming sedentary, preventing ourselves carrying an extra couple of kilos
through lifestyle intervention. What's really fascinating is if you have
got genetic predisposition to be overweight, if you have genetic
predisposition to have type 2 diabetes that environmental factors can
epigenetically change how those genes manifest so that you can
(22:18):
prevent diabetes, for example, by being active. So everybody who's
got parents or grandparents with type 2 diabetes needs to be as
active as they possibly can. They also have to modify
their diet, knowing that if they eat like Mum and Dad,
they're going to end up like Mum and Dad. So
our future is there. We can see it by looking
at our parents, um, by our grandparents and using that
(22:40):
information we can individualise for our own self and go right.
That needs to be my pathway.
Dr Viviane Richter (22:45):
You mentioned epigenetically. What is that?
Prof Katherine Samaras (22:49):
Epigenetics is the science of how we can either turn
up our genetic inheritance or turn it down. So, for example,
if we look at some of the genes for cancer, BRCA,
for example, is a gene that causes breast and ovarian cancer.
But in many families, if you have the gene, you
(23:12):
don't get the condition. And so it can often skip
generations and appear in a granddaughter, whereas it's avoided the
mother or the father, and it's affected a grandparent or
a great grandparent. Why those genes are turned off is
that they get turned off epigenetically, and the science of
how you can do that is fascinating. We know diet
(23:35):
can affect epigenetic regulation of gene expression. We know exercise
has a big role, and that's been shown best for
people with diabetes. It was the Harvard doctors study that showed this.
If you have two brothers and their father had diabetes
and one is active and one is not active, the
one that's active doesn't get diabetes. The inactive one does.
Dr Viviane Richter (23:59):
Can we talk about what is happening at the cellular level,
you've studied epigenetics of fat cells. Can you tell me
about that research?
Prof Katherine Samaras (24:09):
This was research with one of the premier epigenetics in
the universe who we happen to also have at the
Garvan Institute Professor Susan Clark. With Sue's group of scientists
who are epigenetics. We were able to take fat from
people that were undertaking an uncomplicated surgery, who had diabetes,
(24:31):
did not have diabetes and who were overweight or not overweight.
And we were able to look at where our fat
cells actually come from and what the sequence in the
development of that fat cell was going to be. So,
for example, what we found was that the cells that
become our belly fat and people understand belly fat as
(24:52):
the apple shape, carrying that extra fat in the waistline,
they are different to the type of fat cells you
find elsewhere in the body, and that embryologically the genes
that are regulated start to change at the embryonic level.
So from the time we are in the womb, fat
(25:14):
stores are being started to be regulated and set on
a certain path. Now, other work we know from maternal
nutrition during pregnancy is that if women are obese at
the beginning of their pregnancy, or if they gain a
stack of weight during their pregnancy, by which I mean
(25:36):
like 20+ kilos, that the baby will be born overweight
and at five years it's on a trajectory for being
an overweight child, so very much in the maternal environment,
you can actually set the genes for the embryo and
what's going to happen when it's born and what's going
(25:58):
to happen when it's five years old. So this is
an example of maternal nutrition affecting the offspring that is
epigenetic modulated, so you can have certain genes for obesity.
But then, if those genes are exposed to environments of
super nutrition, then you magnify the genetic effect
Dr Viviane Richter (26:22):
With the work that you're doing with all this research,
do you think we'll all live to 100?
Prof Katherine Samaras (26:28):
Many of us are actually reaching 100 now. There are
about 5500 centenarians living in Australia currently, and it's fascinating
to think about how they got there. What were the
conditions that they lived in? Obviously, they lived during the
war they lived during a depression. They've lived through times
of privation. They've also survived the periods of excess that
(26:52):
we've had in the last 50 years. I think it
is possible for people to live a long life with
their faculties intact, meaning perfect brain health. Their cognition is sharp.
They are wise, good heart health. They can walk. They
can exercise, normal metabolism and be free of cancer. Because
(27:13):
we have examples of that all the time. Nutrition plays
a huge role in getting there. And if we look
at the data that we have, and that's admittedly from
observational studies, we know that the Mediterranean-style diet is associated
with longer life. And if we break down the nuts
(27:33):
and bolts of the Mediterranean diet, it's getting our fatty
acids from things like olive oil and from fish and
limited meat. It's getting plenty of fresh vegetables every day.
Notice I didn't say fruit, fruit is full of sugar,
and it's important we get some fruit, but not a
(27:55):
lot of fruit. Every single day. It's important we look
at the Mediterranean lifestyle that physical activity has played a
very large part of those activities, and I'm not suggesting
that we become hunter gatherers, though some people choose to,
and that's wonderful. But we have to break down the
sedentariness of our current lifestyle and be more active in
(28:17):
different ways. We can also learn from the data on fasting.
There's really great data that people who fast, regularly and
for religious reasons live a lot longer. And that's when
you even control for things like smoking and alcohol consumption.
So these are not just people who are fasting. These
(28:37):
are people who also smoke and drink and do a
whole range of other things. But periodic fasting actually upregulates.
We know from cellular experiments and small animal experiments worms,
rodents that you periodically calorie restrict or fast animals. They
will live a lot longer, and the way that that
works is it upregulates all of our antioxidant production. So
(29:01):
at a genetic level, we respond to that caloric restriction
by upping the gene expression of genes involved in mopping
up radicals, free radicals and oxidative stress products that actually
cause inflammation and erode our body systems. So the fasting
side is fascinating as well as we start to scientifically
understand how that operates. I think the other factor with longevity,
(29:26):
and it's really important, is the cognitive side, because if
you get to 100 you want a body that works perfectly.
But you also want the brain that can drive the
body around to do all the things you want to do,
and understanding mental health is really important. One of the
challenges that older people have is loneliness and the way
(29:46):
that social isolation plays in to cognitive decline. That's really important.
Simple things like being able to hear properly, plays into
cognitive decline. If you don't hear you become increasingly socially isolated,
you don't pick up on cues in the environment, and
people start to actually have more accelerated cognitive decline associated
(30:07):
with that. The time-restricted eating has recently been shown to
be very beneficial for people who are trying to lose weight.
What's interesting in all of this is how our circadian
rhythms fit into that time restricted eating pattern. Because we
at a hormonal level sync with the daylight phase. We
(30:28):
actually do our eating during the daylight, and our metabolism
works best. If we eat during daylight hours. We're not
meant to eat through the dark phase, and so when
you think about the hormones that are involved in these
circadian rhythm. It involves hormones like cortisol for insulin. Our
insulin sensitivity changes through the day according to the light
(30:51):
and dark phase. So much of our food storage works
best if we eat during daylight hours.
Dr Viviane Richter (30:59):
So, Katherine, what motivates you in your research?
Prof Katherine Samaras (31:02):
My patients do, so I see what happens to them.
I want to understand better what the mechanisms of disease are,
and I want to be able to offer them better
solutions than what we have currently. I also think our
patients show us the natural history of a condition, and
(31:23):
we can learn so much from an individual's experience. One
of the privileges of being a clinician researcher is that
I get to see what's happening in the hospital in
the consulting room, and I can take that to the lab,
and that is a fundamental part, I think, of breaking
down the conditions that we treat and really understanding and
(31:46):
then being able to translate that back to a meaningful
intervention in the clinic. So that's what I love about
the research that I do, and it's what inspires me
to keep writing grants in the middle of the night
and reviewing papers in the middle of the night and
doing the stuff that actually is what makes up the
research and makes the research productive and and fruitful. So,
(32:10):
you know, that's what drives me. It's coming back to
the patient.
Dr Viviane Richter (32:15):
Katherine. Before we let you get back to the lab,
it's time for the Fast Five. What do you do
in your downtime?
Prof Katherine Samaras (32:22):
I garden. I grow vegetables. I'm an enthusiastic vegetable grower. I
would like to be self sufficient in some of our
vegetables if we possibly can. And then I pickle them
as well. I love fermented foods. It's so good for
the gut microbiome. So the prodigious, um, vegetables that manage
to grow in my garden get pickled if they're not
(32:43):
consumed immediately.
Favourite music. The Lark Ascending by Vaughan Williams. And I'll
tell you why. I find it absolutely peaceful and inspiring,
and it's basically a bird flying up into the summer sky.
And so it represents freedom. It represents the ability to soar,
(33:08):
and it's just the most beautiful, tranquil piece of music.
Dr Viviane Richter (33:12):
That's wonderful. Secret skills?
Prof Katherine Samaras (33:15):
Probably what I do in the garden. Um, give me
an axe. Give me a hoe. Yes. Big machinery, hand yielded,
of course. So you can chop down something. Give me
something to chop down.
Dr Viviane Richter (33:28):
You're hands on, Katherine!
Prof Katherine Samaras (33:30):
It's all that time in the shed.
Dr Viviane Richter (33:32):
What's the most challenging thing you've ever had to do?
Prof Katherine Samaras (33:35):
I do lots of challenging things. So it's hard to
say what the most challenging is. I can say what
challenges me. And that was being a young mum with
a screamer who I couldn't get to settle. My goodness,
the adrenaline was going in a way that it doesn't
when I you know, I'm managing somebody where you know,
(33:58):
their transplants failing, and they've had they've had a cardiac
arrest that doesn't raise my heartbeat. But a bad day
with children often did. I must say, um, so that
that challenged me... scarred me.
Dr Viviane Richter (34:14):
Um, kids are another level of challenge, aren't they?
Prof Katherine Samaras (34:17):
I hope my daughter never listens to this.
Dr Viviane Richter (34:20):
Fantastic. What's your dream holiday, Katherine?
Prof Katherine Samaras (34:24):
My dream holiday would be walking in the mountains somewhere.
High mountains. So the Alps in Switzerland, the Dolomites and
and just, you know, with a backpack and 12 hours
of daylight ahead.
Dr Viviane Richter (34:38):
Professor Katherine Samaras, Thank you so much for speaking with
us on Medical Minds today. It's been such a pleasure
having you.
Prof Katherine Samaras (34:46):
Viviane, it's been a privilege. Thank you.
Dr Viviane Richter (34:48):
If you'd like to know more about Katherine's research or
the work we do at Garvan, head over to garvan.org.au.
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter.
Thanks for listening.
This podcast was recorded on the traditional country of the
(35:09):
Gadigal people of the Eora Nation. We recognise their continuing
connection to land, waters and community. We pay our respects
to Aboriginal and Torres Strait Islander cultures and Elders past,
present and emerging.
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