Systems biology course 2018 Uri Alon - Lecture 8 C - Dynamic Compensation

Summary

The script delves into the dynamics of glucose and insulin in the body, explaining how insulin resistance can lead to an increase in glucose levels. It discusses the concept of dynamic compensation, where the body adjusts to maintain a steady state despite changes in parameters like insulin sensitivity. The talk also touches on the phenomenon of glucose toxicity and its role in diabetes, highlighting the balance between robust control systems and the risk of mutant cell takeover. The speaker explores the evolutionary purpose of glucose toxicity as a defense against rogue cells and the implications for understanding diabetes and aging.

Takeaways

• 📈 Glucose levels increase immediately due to insulin, leading to cell proliferation until a steady state at 5 millimolar is reached.
• 🔄 Insulin resistance, common in obesity, results in higher glucose and insulin levels, altering the body's compensatory mechanisms.
• 🔄 Dynamic compensation allows the body to maintain normal glucose dynamics despite changes in insulin sensitivity.
• 🔍 The concept of 'steady state' is crucial, where the number of cells dividing and dying is balanced to maintain glucose levels.
• 🧬 The body's feedback loops, like the one involving insulin and glucose, are essential for maintaining homeostasis and can be modeled mathematically.
• 📉 In the presence of insulin resistance, the body compensates by increasing insulin production to maintain glucose tolerance, despite the need for higher insulin levels.
• 🚫 Glucose toxicity occurs when glucose levels are too high, leading to cell death and a vicious cycle that can result in type-2 diabetes.
• ⏳ Aging affects cell proliferation rates, which in turn influences the position of stable and unstable fixed points in glucose dynamics, increasing the risk of diabetes.
• 🧬 Glucose toxicity serves an evolutionary purpose by acting as a selective pressure against cells with mutations that misread glucose levels, thus protecting against uncontrolled cell proliferation.
• 🔄 The body's systems are designed to balance the risk of mutant cell takeover and the onset of diseases like diabetes, influenced by genetic background and lifestyle.

Q & A

What happens to glucose levels in the body when insulin resistance occurs?

When insulin resistance occurs, glucose levels initially increase because the body's cells do not respond effectively to insulin. This leads to a higher glucose concentration in the blood.

How does the body compensate for insulin resistance?

The body compensates for insulin resistance by increasing the number of beta cells, which produce more insulin to try to bring glucose levels back to normal.

What is the role of the 5 millimolar glucose level in cell division?

The 5 millimolar glucose level is a critical threshold for beta cells to stop dividing. When glucose levels reach this point, cell proliferation halts.

What is dynamic compensation in the context of the body's response to insulin resistance?

Dynamic compensation refers to the body's ability to maintain the same physiological response to meals despite changes in parameters like insulin sensitivity, through adjustments in the number of beta cells and insulin production.

How does the body's response to glucose change after insulin resistance has developed?

After insulin resistance has developed, the body initially shows an abnormal glucose tolerance test due to the beta cells not having expanded enough to compensate. However, once a new steady state is reached, the glucose tolerance test becomes indistinguishable from before, but with higher insulin levels.

What is the significance of the hyperbolic relationship between insulin and glucose levels?

The hyperbolic relationship signifies that for every unit increase in insulin, there is a corresponding increase in glucose uptake and utilization, which helps maintain glucose homeostasis.

What is glucose toxicity and how does it relate to diabetes?

Glucose toxicity refers to the phenomenon where high glucose levels lead to the death of beta cells. This can result in a vicious cycle where less insulin is produced, leading to even higher glucose levels, which is characteristic of type-2 diabetes.

How does aging affect the body's ability to handle glucose?

Aging typically reduces cell proliferation rates, which can cause the fixed points in glucose regulation to shift, making it easier for glucose levels to cross the threshold into glucose toxicity.

What is the evolutionary purpose of glucose toxicity?

Glucose toxicity serves as a mechanism to eliminate cells that have mutations causing them to misread glucose levels, which could otherwise proliferate uncontrollably and disrupt glucose homeostasis.

How does the body balance the risk of mutant cell takeover and diabetes?

The body balances the risk of mutant cell takeover and diabetes by optimizing the levels of glucose toxicity and the rate of cell proliferation, which can be influenced by genetic factors and lifestyle choices.

Outlines

00:00

💉 Insulin Resistance and Cell Compensation

The paragraph discusses the dynamic relationship between glucose, insulin, and beta cells in the context of insulin resistance. It explains how an increase in glucose levels leads to an increase in insulin production, which in turn affects cell proliferation and death rates. The concept of steady-state equilibrium is introduced, where insulin resistance causes a shift in this equilibrium, leading to higher insulin levels and a compensatory increase in beta cells. The speaker emphasizes the importance of dynamic compensation, where the system adjusts to maintain balance despite changes in parameters like insulin sensitivity. The paragraph also introduces the mathematical concept of rescaling variables to prove the invariance of the system's dynamics.

05:07

🔄 Dynamic Compensation and Biological Systems

This section delves into the broader implications of dynamic compensation in biological systems, beyond just insulin and glucose. It highlights how the body maintains invariant dynamics in response to changes in parameters such as insulin sensitivity and cell division. The speaker uses the example of blood calcium levels and the role of PTH to illustrate similar regulatory mechanisms. The paragraph also touches on how total blood volume can affect insulin dilution and how the body compensates for this. The discussion concludes with the question of how diseases like diabetes arise despite these compensatory mechanisms.

10:18

🚨 Glucose Toxicity and Cell Death

The focus of this paragraph is on the phenomenon of glucose toxicity, where excessively high glucose levels lead to cell death, particularly in beta cells. It explains how high glucose levels can cause an increase in reactive oxygen species, which damage cells and lead to their death. The speaker discusses how this process can create a vicious cycle in diabetes, where cell death leads to less insulin production and subsequently higher glucose levels. The paragraph also introduces the concept of a new fixed point in the system dynamics that is unstable, which can lead to the progression of type-2 diabetes.

15:22

🌡 Aging and the Risk of Diabetes

This section explores how aging affects cell proliferation and the risk of developing diabetes. As people age, cell division slows down, which can shift the stable and unstable fixed points in the system's dynamics. This shift can make individuals more susceptible to glucose toxicity and diabetes. The speaker also discusses the role of genetics and lifestyle in determining an individual's risk for diabetes and how these factors can influence the position of the fixed points.

20:23

🧬 Evolutionary Purpose of Glucose Toxicity

The paragraph delves into the evolutionary rationale behind glucose toxicity, suggesting that it may serve as a protective mechanism against mutations in beta cells. It explains how mutations can lead to cells that misread glucose levels and proliferate uncontrollably, which could be dangerous if not for glucose toxicity. The speaker argues that glucose toxicity acts as a selective pressure against such mutants, preventing them from taking over and causing systemic issues. The discussion also touches on how different genetic backgrounds and historical patterns of feast and famine may influence the positioning of glucose toxicity thresholds.

25:23

🌟 Conclusion and Future Research

In the concluding paragraph, the speaker expresses excitement about the potential to understand complex biological systems through the lens of dynamical systems theory. They highlight the importance of balancing robustness against mutations and other perturbations with the need for flexibility in these systems. The speaker also mentions that their research group is deeply engaged in exploring these phenomena, which have direct implications for understanding aging and disease.

Keywords

💡Glucose

Glucose is a simple sugar that serves as a primary source of energy for the body's cells. In the context of the video, glucose levels are monitored and regulated by the body to maintain homeostasis. The script discusses how an increase in glucose levels can trigger cell proliferation, which is a key mechanism in the body's response to insulin resistance. The video also touches on the concept of 'glucose toxicity,' where excessively high glucose levels can lead to cell death, which is a contributing factor to diabetes.

💡Insulin

Insulin is a hormone produced by the pancreas that regulates blood sugar levels by allowing glucose to enter cells. The video script explains how insulin resistance can lead to higher glucose levels, prompting the body to produce more insulin to compensate. This increase in insulin is part of the body's dynamic compensation mechanism to maintain glucose homeostasis. The script also discusses how insulin resistance can alter the body's steady state, leading to a higher baseline insulin level.

💡Insulin Resistance

Insulin resistance is a condition in which the body's cells do not respond properly to the hormone insulin, leading to higher glucose levels in the blood. The video script uses this concept to explain how the body's cells may proliferate more than they die in response to increased glucose, which is a compensatory mechanism. However, if insulin resistance is not managed, it can lead to a vicious cycle of high glucose and high insulin levels, culminating in type-2 diabetes.

💡Cell Proliferation

Cell proliferation refers to the process by which cells divide and multiply. In the video, it is discussed as a response to increased glucose levels, where the body produces more cells to help regulate glucose. The script mentions that this proliferation is part of the body's feedback loop to maintain glucose levels around five millimolar. However, if cell proliferation becomes uncontrolled, it can lead to glucose toxicity and contribute to the development of diabetes.

💡Steady State

A steady state in the context of the video refers to a stable condition where the rates of certain processes, such as glucose production and consumption, are balanced. The script explains that after insulin resistance, the body reaches a new steady state where the dynamics of glucose and insulin levels are restored, but with a higher baseline insulin level. This new steady state is a result of the body's compensatory mechanisms to maintain glucose homeostasis.

💡Dynamic Compensation

Dynamic compensation is a concept discussed in the video that refers to the body's ability to adjust and maintain the dynamics of a system despite changes in parameters. The script illustrates this with the example of insulin resistance, where the body compensates for reduced insulin sensitivity by increasing insulin production. This compensation ensures that the body's response to glucose remains invariant to changes in insulin sensitivity, thus maintaining glucose homeostasis.

💡Glucose Toxicity

Glucose toxicity is a phenomenon where extremely high levels of glucose lead to cell damage and death. The video script explains that this can occur when glucose levels reach ten millimolar or higher, causing cells to die off. This death of cells can create a new unstable fixed point, leading to a vicious cycle of more glucose and less insulin production, which is characteristic of type-2 diabetes.

💡Fixed Point

In the video, a fixed point refers to a stable state in a system where certain variables, such as glucose and insulin levels, are balanced. The script discusses how changes in the body, such as insulin resistance or aging, can shift these fixed points. For example, with aging, the fixed point for glucose levels may increase, making it more likely for glucose toxicity to occur and potentially leading to diabetes.

💡Reactive Oxygen Species

Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen. In the video, ROS are mentioned as a byproduct of glycolysis, the process by which cells break down glucose for energy. High levels of ROS can cause oxidative stress and damage to cells, particularly beta cells in the pancreas, which can contribute to the development of diabetes. The script discusses how glucose toxicity can lead to an increase in ROS, which in turn can kill beta cells and exacerbate insulin resistance.

💡Mutations

Mutations refer to changes in the DNA sequence that can lead to alterations in the structure or function of genes. The video script suggests that glucose toxicity may have evolved as a protective mechanism against mutations in glucose-sensing mechanisms within cells. By creating a situation where cells with mutations that lead to overproliferation are selectively disadvantaged, glucose toxicity helps to prevent the takeover of these mutant cells, thus maintaining the stability of the glucose regulation system.

Highlights

Glucose levels increase immediately due to insulin, leading to cell proliferation.

Insulin resistance in obesity leads to higher glucose and insulin levels, affecting the body's parameters.

Dynamic compensation occurs when the body adjusts to maintain steady-state glucose levels despite insulin resistance.

The body's response to insulin resistance involves a rescaling of variables to maintain the dynamics of glucose and insulin.

The model demonstrates that the dynamics are invariant to changes in certain parameters, a phenomenon known as dynamic compensation.

Insulin resistance can initially cause abnormal glucose tolerance, but the body can compensate over time.

The body's feedback loop involving glucose and insulin is crucial for maintaining glucose homeostasis.

Glucose toxicity occurs when glucose levels are too high, leading to cell death and a vicious cycle in type-2 diabetes.

The body's response to glucose toxicity is a key factor in the development of type-2 diabetes.

Aging affects cell proliferation rates, which in turn influences the body's ability to maintain glucose homeostasis.

Gluco toxicity serves an evolutionary purpose by providing a selective disadvantage to cells with mutations that misread glucose levels.

The body must balance the risk of mutant cell takeover with the need for dynamic stability, influenced by factors like genetics and lifestyle.

The concept of dynamic compensation is not only applicable to glucose and insulin but also to other body systems like blood calcium regulation.

The mathematical model of glucose and insulin dynamics can help predict and understand the body's response to various health conditions.

The interplay between glucose sensitivity, cell proliferation, and insulin resistance is complex and influenced by multiple factors.

The lecture concludes by emphasizing the importance of understanding the body's dynamic systems in the context of health and disease.

Transcripts

glucose over weeks increases right away

because of the insulin X now says oh

look glucose is increasing I proliferate

more than I die and you get more better

cells more better cells get more insulin

for insulin you get less glucose when

does it stop it stops when glucose

reaches five millimolar again because

that's the only time the cells stop

dividing and so what you have is when

you have insulin resistance like in

people with obesity they have five of

the more glucose I have more better

cells and also more insulin so their

parameter goes down s went down and I

steady-state went up and exactly s times

I steady-state equals constant turns out

because you want and I will prove that

in a second so this gives you this

compensation and if I'm not going to

zoom into the first time skill so I'm

gonna zoom in here so before insulin

resistance so you look at this day here

so this here is weeks right now I want

to look at this day and then this day I

ate three meals fine right now every one

day I get five more glucose I get some

response to these meals and some insulin

response to these meals

now insulin resistant changed and if I

look at a day here not too long after

insulin resistant change this is I'm

still not compensate it's still not at

steady state I give the same meals and I

get so I see something wrong I get long

and slow insulin so here this is

okay this is not okay

so after insulin resistance I see

something changed but then it X goes

back up in this point here I eat the

same meals and I get back exactly intact

the dynamics everything to normal but my

insulin is higher because that's how

compensation works have more insulin and

to get back to the normal state and to

prove that the dynamics are invariant

you need to use just like last time

rescale variables so if you call if you

make a new insulin that's s times

insulin and the new cells that's s time

cells so rescale the variables then you

can notice that this equations are built

so here I write I this is just this this

includes I if I multiply by s here here

in here I get these rescaled parameters

and if I multiply by s here in here I

get rescale parameters and that's

because cells are always make cells

that's the reason you can have X and

then these equations are invariant

equations are invariant to s and also

invariant to Q by the way you can also

rescale make you and so you can prove

just like the ability for change

detection that there's something about

the symmetry of this equation that makes

it that are the fast time scale after

they reach steady state they do cause

glucose of T forgets about s but insulin

remembers so you get higher insulin a it

for lower insulin sensitivity that

exactly met it balances out the

basically you get I twiddle steady state

is some constant and

exactly s times I which gives you this

hyperbolic relationship because these

equations are invariant so that's that's

talked about the nice knife's edge just

better cell insulin glucose model the

right plot and we could see this this

feature which this feature of being

completely invariant to a parameter is

really a very unusual in fact quite

amazing and this feature of being

invariant to parameter it's called

dynamic compensation and the reference

Carine 2016 almost alleyne here

advisement

so in fact we actually solved two

problems at once here one is that we can

now forget about how well other tissues

are listening to me insulin sensitivity

and still get exactly the same meal

response after we compensated so that's

one problem the second problem is the

number of better cells which divide and

die is maintained at a certain size the

certain amount that amount make sure

that look of the five millimolar so the

amount better selves adjusts itself

according to the biological parameters

but doesn't explode to infinity or go to

zero it's exactly the right size so this

circuit does two things right it makes

the dynamics invariant to us and solves

the problem of the knife's edge because

of this feedback loop where the growth

rate is determined by the parameter that

those cells but by the variable that

those cells control we added here X mix

insulin you have this motif here

and and I went to the same motif in

principal seems to happen in other body

systems for example when you look at

control of a blood calcium which is

another very important parameter it's a

fix it around 10 millimolar between

different people that's controlled by

special gland power thyroid gland which

makes a hormone called PTH it's the same

idea

calcium PTH except that the signs are

different PTH makes calcium go down and

calcium increases the production so

these arrows are flipped and calcium

inhibits the production of cells that

make PTH so some of these arrows of -

science but it's exact it's the same

property and indeed parathyroid glands

can grow it's very famous actually you

can have this hyperparathyroidism

diseases of calcium etc similar to

diabetes but so we think is the same

kind of mathematics is compensating

different organ systems I also want to

say that and things like total blood

volume so as you growing up as a kid or

when you become pregnant blood volume

can change that enters this parameter Q

because now it's as if you when you

crease blood volume insulin gets diluted

out you can see and it turns out that

this same way better cells can expand

and shrink to compensate for blood

volume exactly also so as you're growing

your organs can grow just measuring

through their blood glucose that make

exactly enough insulin to be diluted in

your total blood volume so when you

think about it after you think about you

have to say how can the body work with

all these changes and these are very

essential kind of feedbacks that you

have to have on organs feeding back on

their activity they explain myself and

then you say if this is so perfect how

do we get diabetes where these disease

come from

what's going on with diabetes right so I

have more glucose

cells can expand go back everything's

fine so how can you get disease so

that's the last thing I want to tell you

in a in a few minutes how we get there

biddies hear about this just to explain

and say what what what is it here what I

try to say thanks so what I try to say

is so here we have an event of insulin

resistance so before and you have you

had a good glucose towards you necessary

drink 75 grams of glucose and you have a

good glucose tolerance glucose in the

blood

now there's an insulin resistance so in

a scale of a few let's say about a week

after this insulin resistance happens

you'll have an abnormal glucose

tolerance test but that's because better

cells have not yet expanded it takes him

a long time right to grow to exactly

balance out to make it so during and

after you reach steady state after

better cells have reached their new size

the glucose tolerance test is

indistinguishable from before even

though the parameters change what is

different is insulin so you reach the

same glucose stores with higher insulin

why because this is the sensitivity is

lower so you need more insulin to bounce

out it's lower effect now explain

yourself now

that's that's

yes yeah anyway and these arrows are

dependent on sense sensory systems

inside inside the better cells then look

how much glucose there is basically how

much glycolysis they're making and in

the cells you can see they kill

themselves if they're making too much

glycolysis and the reason they're

killing themselves is because the

Colossus makes these reaction reactive

oxygen species the damage to them and

peda cells are extremely sensitive to

this much more than almost any other

cell and then they so oh maybe I should

so they I want to talk about a so if you

change the glucose sensitivity or

anything in the circuit basically this

makes you have too much glucose the

cells were now proliferate more than die

and the end will return back to and

expand and pushing glucose back though

they have to get the glucose back to

five millimolar and otherwise they keep

proliferating

ah okay so let me tell you about why

could there be the questions about where

you get diabetes in general well end

Tony didn't have compensation model

and that's because I basically totally

you only have the truth here there is

unfortunately another or fortunately

another part of this graph again very

well known where if you reach the

regions of ten ten milli molar glucose

debt they start dying

that's called glucose toxicity and

that's very well known phenomenon the

glucose like I said before the better

cells seem to be very raised very very

sensitive to oxidative stress and caused

by glycolysis and they die and that's a

problem because why

and that's related very much to diabetes

because the situation this creates a new

fixed point you see here you have a new

crossing of these two lines and this

fixed point is a big problem because as

long as you're here proliferation is

bigger than death and who and more

better cells and less glucose but if

you're here if because it's very high

over weeks very high over weeks check

out what happens in this rate here death

this region here is bigger than

proliferation death is bigger than

proliferate that means better cells die

here better cells die there's less

insulin less insulin more glucose and

this is an unstable fixed point so this

glucose explicitly leads to an unstable

fixed point I just want to give credit

to the people who just discussed this

glucose oxy city in terms of diabetes

and that's a vicious cycle cycle cycle

more glucose less better cells more

glucose because it less insulin more so

that's a problem and that's that's you

can say a definition of what's called

type-2 diabetes and it happens when

you're better cells get

exhausted insufficient is it so we have

to you have to be here for weeks if

you're if you go back here you can be

fine right before you lost all your

better cells if you go back change your

diet you go back here you can be fine

you flow back but if you're here for too

long you can in principle lose your

better cells and you are unable to

compensate for Google you have big

problems you can have the this vicious

cycle here is caused by glucose toxicity

so this rising iron here creates another

fixed point and that is a big topic of

research as to how to deal with Google

toxicity we said do what is it - what is

Google exists how it happens is this

reactive oxidant species into damage but

I want to ask ya know I didn't say that

I said that in fact that is in this

region they go there number goes down

down down down down

and so you basically don't have enough

insulin to balance your insulin

resistance and you have high glucose

yeah yeah so for example yeah if you

change that's why even if you have tied

to the business you wanna change your

diet to be here

let's blue coats oh you can you can

there you can have in certain stages if

you change your Google you go here you

you you get really big improvement in

your but maybe you think oh maybe you

think of type one diabetes

yeah let's analyze it see why yeah we

say so the quick problem is age is a big

risk factor for type 2 Davies and what

happens with the age is also very

interesting for the age the universal

thing happens in our body is cell

proliferation goes down cells divide by

less quickly so what happens if

proliferation goes down here it is graph

let's just analyze it this is what

happens with age

so one thing you can observe is if for

healthy people the fixed point creeps up

so that's well known with age instead of

five you have five point five five point

six but this one the unstable fixed

point moves to lower glucose levels see

so that's like now this Google toxicity

is really depending on genetics you can

get it at higher or lower glucose level

so here is genetics plays in right where

the position of these fixed points and

your lifestyle accent determines the

fluctuations and glucose so all this

together

tie into like we can start to understand

why these risk factors affect something

so complex like a diabetes like a

disease like that yeah how they can be

understood in terms of dynamical system

at least a very simplified way but you

can can give you some ideas right do you

explain myself with this points aging

proliferation goes down the fixed points

come closer together and it's more risky

that glucose will cross this threshold

and you get all white okay so let's

finish up with this question just fish

it why does our body have gluco toxicity

is it just an annoying byproduct of

cells the cells are weak and lazy right

- my high glucose they eat a lot early

that's maybe like why is it does it have

to be that way they'd have to be that

way and so what is the evolutionary

purpose of side of Google toxicity yes

right because in biology at least we

want to not reject the hypothesis we

want I think we should start with a

positive if you see something important

it has a reason it has a reason and

maybe you find out that there's no

reason okay but the initial philosophy

should say there is a reason let's find

out and it turns out that it has a

really crucial reason and that is to

address the third problem mutations look

if we didn't have bucco toxicity if this

was our perfect control circuit with

just one stable fixed points suppose I

can engineer would build it right great

an engineer would build it but engineer

doesn't have to worry that the little

thermostat gets mutations okay well she

have to worry so the bad cells are

dividing dividing dividing they make

themselves better cells or stem cells

apparently they do now once in a while

so they transport glucose and they have

like proteins like Luca kinase it

phosphorylates glucose and you know once

in a while in this division you get a

mutant now you get a lots of measles but

if you get a mutant in the sensory

system of glucose for example a gluco

kinase that phosphorylates glucose too

much seven in the cell this mutant self

thinks there's more glucose than there

actually is okay so once in a while

you'll get a mutant that thinks or

senses miss reads I'll call it miss

reads glucose as it's more than the

actual level so it could be in other

contexts would be a receptor that's

firing too much or acceptor that's lost

you always have to worry about those

cells and this occurs very often so once

every and estimated anagram of tissue

okay over a 80-year lifespan you'll get

every possible mutation in the genome a

thousand times you have an example of a

cell with agitation a thousand

times just because Tichenor is ten to

the minus nine if ten to the nine cells

per gram you have this a division once

per month you multiply everything how

many of months in the lifetime if not

thousands 100 or 10,000 bits a lot right

now what's the problem those mutants the

body as in the blood everything is fine

is 5 milli molar

but those mutants think there's 20 milli

molar so what will they do what will

they do now proliferate so certain

mutants because of this feedback loop

will proliferate will grow they have an

advantage over their brothers and

sisters and eventually they'll take over

that little island now ok so yeah but

that's not so good because now you have

all these better cells it's you really

have five in the mode but all their

cells think there's twenty millimolar

what will they do they'll create so much

insulin to push insulin back to what

they think is five millimolar but

exactly I'd say 1 millimolar and then

you die so meters will proliferate take

over push glucose down to what they

sense as 5 millimolar and then you die

so that's not good so what is glucose of

Sicily do

look at accessory basically kills the

strong strong mutants because for them

they die more than the right so it gives

mutants that mystery the signal a

selective disadvantage and that's the

way we think that if because of organ

sized problems and robust is to

parameters you need to have a feedback

loop over cell proliferation it's based

on the control signal glucose but then

inherently mutants in that read the

signal certain mutants will have a

growth advantage and will spoil the

system is very dangerous so you need to

have a biphasic situation where you have

to have like a to art like a drop and

then arise and death rate or a

proliferation or something in order to

get rid of those strongest mutants it's

just that there's still sensitivity to

mutants that miss read here which is

still these mutants here that miss read

the signal from five it's still a

problem so you can do certain things to

deal with that like make these islands

so that Amita takes over only an island

or not the entire thing and make the

proliferation rate small there and slow

down proliferation we think that's what

sets the slope will appear in race to

the age for example you can yeah is

there less and less of a problem but

they're still then you can basically

I've need to optimize how close you put

this glucose accessory how wide you to

optimize it because in one hand it

protects you against mutants on the

other hand makes you prone to diabetes

so it's like and that depends on your

lifestyle so there's a certain rodents

called a some onyx someone some both o

besos right now

they roll in to live here in the desert

and if you give them you into a lab and

you give them a regular food for mice

they get a Google Doc City and they die

basically so because they're used to

very they're really fasting diet and

what happens well as evolution pushed

this vice this

toxicity very close here this is in this

Simonis or basis because they rarely go

above they don't a problem with their

lifestyle you can see because they eat

they show shits my Lewis all these like

very great and so in different genetic

backgrounds probably also push this in

differently and we see that in different

ethnic backgrounds depends on a recent

pass of a starvation in history and

feast famine so so you can balance they

see the risk between a mutant take over

and dynamic instability this this is a

big lecture we talked about robustness

to three different things organized

controlled vibration and parameters

dynamic compensation how we can have

equations that whose dynamics is

invariant to a parameter of a distant

issue resistant to mutation and more

generally how to take our way of

thinking to the level of not proteins

and cells same way of thinking two level

of balance between different organs in

the body

hormonal systems that this field is very

fresh and of course much more to explore

as you can see it's linked directly to

aging diseases and that's say right now

taking major research interest in my

group is just to understand these

phenomena and basically I'm kind of in

love with this possibility right now I

hope you enjoyed it

I wish you a lot of health and see you

next week