Lecture notes
Class notes BI644 Biology of Ageing Week 4-5
- Institution
- The University Of Kent (UKC)
Class notes for BI644 Biology of Ageing Week 4-5
[Show more]
Seller
Follow
Content preview
4.1 Dietary RestrictionNutrient Regulated Pathways and Processes
It is important to think about the insulin and TOR signalling pathways as they are both nutrient
regulated.
The insulin signalling pathway becomes
important when we eat, as when we eat,
our blood sugar increases, and our
pancreatic beta cells release insulin. This
goes to the adipose cells which then forces
them to take up glucose and blood sugar
levels decrease. During exercise, glucagon is
released from pancreatic alpha cells and the
liver breaks down glycogen to glucose. It is a nutrient sensitive
pathway.
The activity of the TOR pathway is geared towards getting the cells to
grow - it is a growth stimulating pathway. it is stimulated by insulin
through the insulin stimulating pathway, and also amino acids which
come from proteins being broken down. This is a very important
nutrient regulated pathway.
Diet/dietary restriction means you are eating 60-70% of ad libitum food levels, but there is a
sufficient amount of vitamins and minerals. You have cut down the amount of food you normally eat
(fewer calories) but you are not starving or malnourished. The diet can also be manipulated in other
ways where you change the balance of the diet, i.e., change the amount of protein, sugar, etc.
How Do You Dietary Restrict a Model Organism?
Worms
o Worms are grown on agar plates that are seeded with bacteria
o Dilute bacterial food and antibiotics to the medium so the bacteria cannot grow any
further once on the plate
o Genetically using a pumping deficient mutant, e.g., eat-2
Flies
o Serial dilution of yeast and/or sugar in their food and this gives a reduced calorie
intake
Mice
o Reduced chow provided. Normally mice can eat as much chow as they so it is
continuously topped up
Primates
o Reduced amount of food
Dietary Restriction Extends Lifespan
If you decrease the amount of food given
to a worm, fly or mouse, then lifespan will
be extended. (Fully fed organism = blue,
DR = red)
,DR also seems to reduce the incidence of almost all age-related diseases and pathologies.
One of the first experiments done was by McCay et al. in 1935. He showed that if you dietary
restricted rats, there was a 20-40% increase in lifespan.
Primate Lifespan Studies
There were two DR studies conducted on primates. The first of these,
conducted by UoW, showed that if you calorie restrict a primate (a rhesus
monkey), then you can extend the age related mortality, the survival of the
monkeys increased. At the time this study was published, in 2009, the
monkeys had aged to around 30 years. The experiment took place over a long
period of time and several generations of people in a lab were responsible.
The University of Wisconsin followed up on the study
in 2009 and updated the data. They showed that the
trend continued, even with the older monkeys.
Calorie restriction was extending lifespan and also
not only age-related mortality, but also all causes of
mortality as well.
However, shortly after the first primate study was
published, another one was published by the NIA. In this study, they
showed that calorie restriction did not have any effect on the lifespan of
the monkeys. In this experiment, they broke the data down into males
and females. The data shows that the lines for the DR males and females
and their control counterparts are overlapping. The statistics also show
that there is not much of a difference.
Why the Difference?
The two labs worked together to find out why there was such a big
difference in their results. They found that there was a difference in the
starting diets. The diet in the NIA monkeys was a lot healthier to begin
with so they lived for longer, so the DR was not protecting against this.
Whilst the monkeys in the first study were on a high sugar diet, so DR
restriction protected them from this and they lived longer.
The two sets of scientists working on these studies came together and
did an analysis on all the animals together to look at it in more detail
and find the link between dietary restriction and lifespan. When they
put all the data together, they found that calorie restriction did have a
good, positive effect on preventing age related morbidities.
With calorie restricted animals, there was a much larger percentage at
all ages that did not have any age-related morbidities. If you look at
both groups, the calorie restricted group, in red, have a lesser degree of
cancers, better insulin resistance, lower diabetes, and in general
improved cardiovascular disorder.
Overall, calorie restriction does improve the health of primate
populations, or at least rhesus monkeys.
, Another study in mouse lemurs showed that calorie restriction also
extended lifespan.
The experiments in the model organisms show that calorie restriction
extends lifespan. Since these experiments have been done, many
labs have looked at a lot of other species, for example Labradors,
chickens, beetles, yeast, etc. They have shown that dietary restriction
has a positive effect on lifespan and health in all of these animals.
Effects of DR in humans
There was a paper in The Lancet in 2017, which summarises all the positive effects of dietary
restriction on humans.
It is hard to do a human lifespan trial, but it is possible to do a healthspan trial in humans by looking
at groups of people who have undergone
dietary restriction to see the effects on their
health.
If you calorie restrict yourself, you will be able
to preserve brain function, delay osteoporosis,
protect against arthritis, protects against
cardiovascular disease, prevent age related
diabetes and lower the incidence of cancer, as
well as a few other positive effects.
An Example of the Effects of DR on Human Populations
Okinawa is an island found off the coast of Japan. It has the highest fraction of centenarians in the
world. They have a culture where they eat less than most Japanese people. Children only eat around
60% of recommended calories, whilst adults eat 20% less than national average.
It is a self-imposed DR culture and there is a saying called ‘Hara hachi bu’ which means Eat until belly
80% full.
Not only is there a higher population of centenarians, they also have reduced morbidity. Compared
to Americans, they are a lot more likely (75%) to retain their brain function (cognitive ability), much
less cancer incidence (80% fewer breast and prostate cancers and 50% fewer ovarian and colon
cancers), 50% fewer hip fractures and 80% fewer heart attacks.
This shows that there can be a cultural effect on diet, that can have a knock-on effect for health as
well. Sadly, an American airbase was built in Okinawa recently and a lot more fast food came into
the culture. Now, some children have an obesity problem as they are not used to dealing with that
amount of calories in their diets.
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller uniofkentdocs. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £12.99. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
64438 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy revision notes and other study material for 14 years now