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  • Nine years ago, I found myself in a doctor's office, contemplating

  • the nature versus nurture debate from a fresh perspective.

  • You see, I had been trained as a geneticist

  • and had spent my career manipulating DNA

  • and seeing the profound consequences in a lab setting

  • so I'd always put my money

  • more on the nature, or the genetic side of the debate.

  • But, as my doctor revealed to me that I was pregnant with identical twins,

  • I realized that my convictions were about to be put to the test.

  • For starters, we had not budgeted on two daycare bills at once.

  • So I have half-jokingly started to wonder what would be the consequences

  • maybe, if we just sent one twin to daycare

  • and maybe just kind of tuck the other one in my office drawer during the workday.

  • (Laughter)

  • Despite their identical DNA, I somehow doubted

  • that things would turn out all that well for the twin in the office drawer.

  • (Laughter)

  • Identical twins have had a profound impact

  • on scientists' understanding of nature and nurture.

  • Studies on identical twins who were separated at birth

  • and raised in separate households have helped us understand

  • different traits that are more affected by nature, or DNA,

  • versus nurture, or the home environment.

  • For example, some traits, like IQ or criminal tendencies,

  • are more affected by your DNA than the house that you grew up in.

  • On the other hand, other traits, like depression in men,

  • or your preference for a particular political party,

  • are more influenced by your environment than by your genes.

  • What about identical twins who are raised in the same home environment?

  • Their nature and their nurture are almost the same.

  • And yet, any parent of identical twins, myself included,

  • can quickly point out differences in their children.

  • One twin may have more of a preference for certain types of foods,

  • or may have more aptitude for a certain sport or musical instrument.

  • And sometimes, health differences can arise in these children.

  • For example, there are reports of autism,

  • or asthma, or bipolar disorder

  • arising in one twin at a young age while the other one remains unaffected.

  • How do we explain these differences,

  • given that the DNA is the same in these children?

  • And for the large part, their home environment has been the same too.

  • Well, it turns out that some of these differences can be explained

  • by a third, very powerful influence on our lives, besides nature and nurture.

  • This is epigenetics.

  • I'm going to talk to you today about what epigenetics is

  • and how it impacts your life, even if you're not an identical twin.

  • Before we talk about epigenetics, we need to consider our DNA

  • and how it fits into our cells because, believe it or not,

  • of the 50 trillion or so cells in your body,

  • each one contains about six linear feet of DNA.

  • If we were to stretch it out, it would be about as tall as a pretty tall man.

  • So how in the world do we fit that amount of genetic material

  • into something the size of a cell nucleus,

  • which is 400,000 times smaller?

  • Well, the answer is that we do it by wrapping our DNA

  • around clusters of proteins called histones.

  • You can think of histones like molecular spools.

  • There are about 30 million of these spools in each of your cells.

  • So this helps explain how you fit

  • such a tremendous amount of DNA into a small space.

  • We call this combination of histones and DNA, chromatin.

  • While chromatin solves

  • this tremendous packaging problem that the cell has,

  • it also presents a new one for the cell.

  • This is one of DNA accessibility because keep in mind

  • that the functional units of DNA are actually the genes encoded in it.

  • These are the instructions for the cell.

  • There are what tell the cell what to do and who to become

  • and yet, when these genes are tightly compacted into a chromatin structure,

  • the cell in unable to read them, they might as well not even be there.

  • This is where epigenetics comes in.

  • 'Epi' meaning 'on top of' and 'genetics', your 'genes',

  • literally refers to a set of instructions

  • that sits down on top of our DNA and our histones.

  • Epigenetic marks are small chemical tags which sit down on our chromatin

  • and can help instruct it whether to compact or decompact.

  • Those instructions can then affect

  • how the cell reads the underlying genes encoded in the DNA.

  • So, to show this schematically,

  • some Epigenetic marks, shown here in red, can help condense chromatin.

  • When they do this, they obscure the underlying genes,

  • preventing the cell from being able to read them.

  • They turn those genes off.

  • Other Epigenetic marks, shown here in green,

  • can help decondense the chromatin.

  • When they do this, the gene becomes accessible to the cell,

  • the cell is able to read it and turn it on.

  • These types of Epigenetic marks are profoundly influential to our biology.

  • Consider, for example,

  • what is it that makes our cells different from one another,

  • what makes them look and behave differently,

  • what is it that makes a muscle cell, for instance,

  • look different from a neuron?

  • After all, these cells contain exactly the same DNA

  • but it's their Epigenetic instructions that help tell them

  • which genes to turn on and which ones to turn off.

  • With those different genes at play, these can become very different cells.

  • You might be wondering when does all this Epigenetic information

  • get laid down on our chromatin?

  • The answer is that much of it happens during our embryonic development.

  • Interestingly, when you were first conceived,

  • and you were just comprised of a few, undifferentiated embryonic stem cells,

  • which had the potential to become any cell in your body,

  • your chromatin didn't have many Epigenetic marks on it.

  • It was only as your cells began to divide

  • and receive signals and information from surrounding cells,

  • that the Epigenetic marks began to accumulate

  • and then the genes began to get turned off and turned on,

  • and the muscle cell became very different from the neuron.

  • This brings me to a really important point about epigenetics.

  • Epigenetic marks can be influenced by the environment.

  • When I say environment, I don't just mean the surrounding cells

  • that tell a neuron to become a neuron.

  • I also mean, the environment outside of the developing embryo.

  • So the food that the mom eats, or the pre-natal vitamins that she takes,

  • or the cigarettes that she smokes,

  • or the stresses that she encounters at home or at work,

  • can all be transmitted as chemical signals

  • through her bloodstream to her developing fetus,

  • where they can get laid down as Epigenetic marks

  • that affect the fetus' own genes and long-term health.

  • This has been shown experimentally in mice.

  • Mice contain a gene called agouti, which makes them obese and yellow

  • and susceptible to diseases, like cancer and diabetes.

  • This gene and these traits can be passed down

  • from generation to generation through DNA so that an agouti mother will give rise

  • to a fat, yellow, disease-susceptible offspring,

  • if that offspring contains the agouti gene.

  • Here's something interesting about the agouti gene.

  • It can be turned off, if silencing Epigenetic marks accumulate around it.

  • So, if a pregnant agouti mother is fed a diet

  • which is supplemented with these silencing Epigenetic marks,

  • those marks will be chemically transmitted to the DNA of her embryo,

  • where they'll accumulate around that agouti gene

  • and effectively turn it off.

  • Her embryo will maintain those marks.

  • So it will be born and grow up

  • to be an adult mouse that's thin, and brown, and healthy.

  • Even though this mother is genetically identical

  • at the DNA level to both sets of this offspring,

  • you can see that the diet that she consumed during her pregnancy

  • can affect the health and appearance of her offspring.

  • This has, of course, implications beyond the mouse world,

  • because studies in humans have shown

  • that women who don't eat well during their pregnancy, who eat bad foods,

  • will go on to have children

  • who are more susceptible to developing obesity and cardiovascular disease.

  • Likewise, if women smoke during their pregnancy,

  • their children will grow up to have a greater chance of developing asthma.

  • These correlations between maternal behavior during pregnancy

  • and the long-term health consequences for their offspring

  • are thought to be linked by epigenetics,

  • much as you've seen here in the case of mice.

  • Another important point to make about epigenetics is

  • that these types of marks can be transmitted

  • not only from a pregnant female to her fetus

  • but also from generation to generation

  • if the marks are put down on our sperm or eggs.

  • So, if you're in the audience and you're not pregnant,

  • and you're not even thinking about conceiving, think about this,

  • because the lifestyle decisions that you make today

  • can still affect future generations.

  • For example, a long-term study was conducted in Sweden and England

  • that showed that young boys who overate or started smoking

  • during their pre-pubescent years, as their sperm was starting to develop,

  • went on to have sons and grandsons with significantly shorter lifespans.

  • It's believed that the Epigenetic marks

  • that were transmitted by their diet and smoking decisions,

  • affected the long-term health of their future generations.

  • This type of Epigenetic information, of course, can also be passed

  • through females to their daughters and granddaughters,

  • if the Epigenetic marks are laid down on their eggs.

  • The idea of transgenerational inheritance of Epigenetic marks

  • is still being debated and studied in terms of humans, but I should add

  • that in non-human organisms, mice, flies, worms,

  • there's mounting evidence that this theory holds true.

  • In fact, it's being shown in the lab that over tens of generations,

  • Epigenetic marks can be passed down.

  • Another thing to know about epigenetics is that they don't just affect us

  • when we're a developing embryo,

  • or when the sperm and egg that conceived us were developing,

  • they can also affect us after our birth.

  • This is particularly relevant as we think about our brains

  • which continue to grow and develop throughout our lives.

  • Take this example from rats.

  • Rats contain a gene called the glucacorticoid receptor

  • and this gene can be expressed, or read, in a certain region of the rat's brain.

  • When it is, it helps the rat cope with stressful situations.

  • So, the more receptor that the rat has in this region of the brain,

  • the better it will handle stress.

  • There are studies that have shown that interactions

  • between a rat mother and her pups during the first week of their life

  • can have long-term consequences for how much glucacorticoid receptor

  • those pups will grow up to have in their brains

  • and therefore how well they will handle stress.

  • This is how this works.

  • When rat pups are born, their glucacorticoid receptor gene

  • is surrounded by a number of these silencing Epigenetic marks.

  • This effectively turns the gene off.

  • Yet, if a rat mother extensively licks and grooms on her pups,

  • basically takes good care of them, during the first week of their life,

  • those Epigenetic silencing marks can be removed from the gene.

  • This allows the glucacoid receptor gene to turn back on,

  • and it stays on in those pups' brains throughout their lives.

  • So they grow up to be well-adjusted animals

  • who deal well with stress.

  • If a rat mother ignores her pups

  • (Laughter)

  • that glucacoid receptor gene will maintain those silencing Epigenetic marks,

  • they won't go away, and they'll stay in those pups' brains throughout their lives.

  • These rats will grow up to be very anxious in stressful situations.

  • This actually brings up a really encouraging point about epigenetics

  • in that Epigenetic marks are reversible.

  • So, if you've been sitting in the audience

  • cursing your parents and your grandparents

  • for their poor lifestyle decisions, or for the lack of licking and grooming

  • (Laughter)

  • that you've received as a baby, take heart

  • because scientists are making terrific progress

  • in designing drugs that can reverse toxic Epigenetic marks

  • to help combat certain diseases.

  • This is especially looking promising in the case of certain cancers

  • which happen to be affected or turned on by aberrant Epigenetic marks.

  • This is how this can work.

  • Our bodies have certain genes in them called tumor-suppressor genes.

  • The job of these genes is to protect cells from becoming cancerous.

  • But if too many silencing Epigenetic marks start to accumulate around these genes,

  • the genes get turned off,

  • and they can no longer perform their job of protecting the cell.

  • So scientists have developed drugs which have undergone FDA approval,

  • and they're in a clinical setting, which can target these silencing marks

  • effectively removing them from the tumor-suppressor genes

  • and allowing these genes to go back to their job of protecting the cell.

  • Now think about it.

  • This is a radical departure from traditional cancer therapy.

  • Historically, we've always been focused on killing cancer cells.

  • This, however, is taking the approach of restoring cells to their original nature,

  • reminding them of what they're supposed to do.

  • This type of therapeutic approach is showing great promise

  • in terms of other diseases as well, besides cancer,

  • diseases that are also similarly affected by aberrant Epigenetic marks,

  • like diabetes, and lupus, and asthma,

  • and certain neurological disorders, Huntington's and Alzheimer's diseases.

  • I'm optimistic that this type of therapy is going to hold great promise

  • for our health in upcoming years,

  • but I should caution that one of the challenges as we go forward

  • is figuring out how to target these drugs toward toxic Epigenetic marks

  • while leaving alone the beneficial ones that help maintain our health.

  • I want to conclude by emphasizing

  • that there are things that we can do now to positively influence our epigenome.

  • It's not too late to start eating healthier foods,

  • foods that we already know are good for us,

  • like leafy vegetables, whole grains, avoiding cigarettes, cocaine, stress

  • all of which have been shown experimentally

  • to impact our epigenomes negatively.

  • These are things that you can do

  • to impact your genes and your long-term health.

  • And if that's not incentive enough,

  • they can also impact the health of your future children and grandchildren.

  • I think this concept, that we can positively impact our genes,

  • is really profound and empowering

  • because we've always worked under the assumption

  • that our genes are set in stone, that they're beyond our influence.

  • I want to end today by challenging you, and myself,

  • to take the opportunity that we have before us

  • to positively impact our long-term health

  • by treating our epigenome kindly, through healthy lifestyle decisions.

  • Thank you.

  • (Applause)

Nine years ago, I found myself in a doctor's office, contemplating

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【TEDx】表觀遺傳學和我們基因的影響|Courtney Griffins|TEDxOU (【TEDx】Epigenetics and the influence of our genes | Courtney Griffins | TEDxOU)

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    Kelvin 發佈於 2021 年 01 月 14 日
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