NOVA | Epigenetics

Summary

The video script explores the concept of epigenetics, revealing how identical twins, with the same DNA, can diverge in appearance and health due to changes in their epigenome. It discusses the influence of environmental factors and lifestyle on gene expression, as demonstrated through studies on mice and twins. The script also highlights the potential of epigenetic therapy in treating diseases like cancer by altering gene instructions rather than killing cells, offering hope for disease management and prevention.

Takeaways

• 👥 Identical twins, despite having the same DNA, can exhibit different physical appearances and health conditions as they age due to epigenetic changes.
• 🧬 Our genes define who we are, but they are not the only factor; epigenetics, which can work with or against our genes, also plays a significant role.
• 🔍 Researchers at Duke University, led by Randy Jirtle, have shown that genetically identical mice can have different physical traits based on the presence of a methyl group, which can turn genes on or off.
• 🐭 The study of mice revealed that the epigenome, a sort of second genome, can be altered by environmental factors such as diet, affecting gene expression and potentially leading to health issues like obesity.
• 🌱 Epigenetic changes can be passed down through generations, meaning that what a mother or even a grandmother ate could affect the health of their descendants.
• 🧬🌿 Epigenetics is the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.
• 🧪 In a study of identical twins, it was found that as they age, their epigenomes can diverge significantly, especially when their lifestyles differ.
• 🧬🔄 Epigenetic instructions can change during critical periods like puberty or pregnancy, which can lead to different gene expressions in cells.
• 🏥 Epigenetic therapy is a new approach to treating diseases like cancer, which focuses on changing the behavior of cells by reactivating genes rather than killing them.
• 💊 Epigenetic drugs have shown promise in clinical trials, with some patients achieving remission without severe side effects.
• 🌱👶 The epigenome is not only influenced by what we do but also by what our ancestors did, emphasizing the importance of lifestyle choices for future generations.

Q & A

What is the main point discussed in the video about identical twins?

The video discusses how identical twins, despite having the same DNA, can exhibit different physical appearances and health conditions due to epigenetics, which involves changes in gene expression that do not involve alterations to the underlying DNA sequence.

What is the role of genes in determining who we are?

Genes play a significant role in determining who we are by providing the instructions for making proteins, which are essential for the structure and function of our bodies. However, genes are not the whole story, as epigenetic factors can influence gene expression and thus our traits and health.

What is the significance of the study conducted by Duke University's Randy Jirtle on mice?

Randy Jirtle's study on mice demonstrated that epigenetic changes can occur even in genetically identical organisms, leading to different physical characteristics such as size and coat color. This suggests that environmental factors and diet can influence the epigenetic marks on our DNA, affecting traits and potentially health.

What is the epigenetic explanation for the differences observed in identical twins as they age?

As identical twins age, their lifestyles, diets, and environmental exposures can lead to the accumulation of epigenetic differences. These differences can result in changes to gene expression, which may manifest as physical or health disparities between the twins.

What is the epigenome, and how does it relate to the genome?

The epigenome refers to the chemical modifications to the DNA and associated proteins that regulate gene expression without changing the underlying DNA sequence. It acts as a layer of information 'above' the genome, influencing which genes are active or silent in different cell types.

How can the epigenome be influenced by environmental factors?

Environmental factors such as diet, exposure to toxins, and lifestyle can influence the epigenome by adding or removing chemical tags like methyl groups to DNA and associated proteins, which can turn genes on or off and affect gene expression.

What is the potential impact of epigenetic changes on human health?

Epigenetic changes can have profound implications for human health. They can influence susceptibility to diseases, including cancer, and may also affect the health of future generations by altering gene expression in ways that are inherited.

What is the concept of epigenetic therapy, and how does it differ from traditional cancer treatments?

Epigenetic therapy aims to modify the epigenetic marks on DNA to reactivate silenced genes or inhibit overactive ones, rather than killing the cells as in traditional cancer treatments. This approach seeks to remind cancer cells of their normal function and behavior, potentially offering fewer side effects.

How were epigenetic differences in identical twins studied in the Madrid research?

In the Madrid study, researchers collected cells from 40 pairs of identical twins and analyzed their DNA for epigenetic modifications. They observed that the epigenomes of older twins, especially those with different lifestyles, showed more dramatic differences compared to younger twins.

What does the video suggest about the responsibility individuals have regarding their epigenome?

The video suggests that individuals have a responsibility to consider how their actions, such as diet and lifestyle choices, can potentially alter their epigenome and that of their future generations, emphasizing the importance of making healthy choices.

What is the potential of epigenetic therapy in treating diseases like cancer?

Epigenetic therapy holds promise in treating diseases like cancer by targeting the chemical tags that control gene expression, rather than the genes themselves. This approach can reactivate normal gene function in cancer cells, potentially leading to remission with fewer side effects compared to traditional treatments.

Outlines

00:00

🌟 Identical Twins: Beyond the Genes

This paragraph explores the concept that identical twins, despite having the same DNA, can exhibit different physical traits and health outcomes as they age. It introduces the idea that genes are not the sole determinants of who we are, and that epigenetics—the study of changes in organisms caused by modification of gene expression rather than the alteration of the genetic code itself—plays a significant role. The narrative uses the example of mice with identical DNA but different physical appearances and health statuses due to epigenetic modifications, highlighting the work of Duke University's Randy Jirtle, who investigates how the epigenome can influence gene expression and potentially affect health outcomes, including obesity and disease susceptibility.

05:00

🔬 The Epigenetic Influence on Health and Heredity

The second paragraph delves into the impact of epigenetics on health and how it can be influenced by environmental factors such as diet. It explains the epigenome as a layer of instructions that dictate how and when genes are expressed, differentiating cell types in the body. The Madrid study of identical twins is highlighted, showing how epigenetic differences accumulate over time, especially when twins lead different lifestyles. The research indicates that these epigenetic changes can be inherited by subsequent generations, suggesting that the health of future generations could be influenced by the environmental exposures and behaviors of their ancestors.

10:02

🛡️ Epigenetic Therapy: A New Approach to Disease

The final paragraph discusses the potential of epigenetic therapy in treating diseases like cancer, which can be influenced by the silencing of critical genes. It contrasts the traditional view of cancer as a disease of broken genes with the newer understanding that epigenetic tags can be manipulated to reactivate genes and revert cancerous cells to a normal state. The narrative shares the story of individuals who have participated in clinical trials for epigenetic therapy, resulting in remission for some patients. It concludes with a call to action for individuals to be mindful of their actions, as they have the potential to positively or negatively affect their own and their offspring's epigenome.

Keywords

💡Identical Twins

Identical twins are siblings that develop from the same fertilized egg and therefore have the same genetic material. In the video, the concept of identical twins is central to exploring the theme of epigenetics, as it highlights how two individuals with the same DNA can develop different physical traits and health outcomes. The script mentions how twins may start out looking the same but diverge in appearance and health as they age, exemplified by one twin having more gray hair than the other.

💡DNA

DNA, or deoxyribonucleic acid, is the molecule that contains the genetic instructions for the development, functioning, growth, and reproduction of all known living organisms. The script discusses how identical twins have the 'exact same genes' and thus the same DNA, setting the stage for the exploration of epigenetics and how it can influence gene expression differently in genetically identical individuals.

💡Epigenetics

Epigenetics is the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself. The video emphasizes the role of epigenetics in how environmental factors and lifestyle choices can influence gene expression, leading to differences in health and physical appearance among identical twins. The term 'epigenome' is used to describe the complete set of epigenetic marks on the genome.

💡Gene Expression

Gene expression is the process by which the information encoded in a gene is used by the cell to produce a functional product, like a protein. The video script illustrates how epigenetic changes can turn genes on or off, affecting gene expression. For example, the script describes how a methyl group can attach to a gene, shutting it down and leading to observable differences like obesity in genetically identical mice.

💡Methyl Group

A methyl group is a chemical tag consisting of one carbon atom and three hydrogen atoms (-CH3). In the context of the video, methyl groups are highlighted as epigenetic markers that can attach to DNA and influence gene expression. The script uses the example of a methyl group attaching to the 'AI Gene' in mice, shutting it down and affecting the mouse's coat color and obesity.

💡Histones

Histones are proteins that DNA wraps around to form chromatin, which helps package the DNA into chromosomes within the cell nucleus. The script explains that epigenetic changes can involve histones, where chemical tags can influence how tightly DNA coils around histones, thereby controlling gene expression. This is part of the epigenetic regulation that can lead to different cell types and functions.

💡Epigenomic Tags

Epigenomic tags refer to the chemical modifications on the DNA and histones that do not change the DNA sequence itself but can affect how genes are expressed. The video script describes how these tags, such as methyl groups, can be influenced by diet and environmental factors, and how they can be inherited across generations, affecting traits like coat color in mice.

💡Disease Susceptibility

Disease susceptibility refers to the likelihood that an individual will develop a particular disease based on genetic and environmental factors. The script discusses how identical twins, despite having the same DNA, can have different susceptibilities to diseases like cancer due to epigenetic differences, as seen in the contrasting health outcomes of Anna Marie and Clotilde.

💡Clinical Trials

Clinical trials are research studies that involve human volunteers to test new medical interventions. The video mentions a clinical trial involving epigenetic therapy, which aims to change the behavior of cancer cells by reactivating silenced genes. The script provides an example of patients like Sandra Shelby and Roy Kwell who participated in such a trial and experienced remission.

💡Epigenetic Therapy

Epigenetic therapy is a type of treatment that targets the epigenetic modifications of cells, rather than the genetic mutations themselves, to treat diseases. The video script describes this therapy as a 'diplomacy' approach that aims to change the instructions of cancer cells by reactivating genes, leading to remission in some patients without the severe side effects associated with traditional cancer treatments.

💡Genome

A genome is the complete set of genetic information of an organism, including all of its genes. The script uses the analogy of a computer to explain the relationship between the genome and the epigenome, with the genome being the hardware and the epigenome being the software that dictates how and when the genetic information is used to create different cell types and functions.

Highlights

Identical twins, though sharing the same DNA, can exhibit subtle differences in appearance and health as they age.

Genes alone do not fully determine who we are; epigenetics plays a crucial role.

Epigenetics refers to changes in gene expression that can be influenced by factors like diet and environment.

Researchers at Duke University have discovered that a methyl group can modify genes, affecting traits such as obesity in mice.

The epigenome, a collection of chemical tags, can control gene expression and is considered a 'second genome'.

Epigenetic changes can be passed on as cells divide, but they are not necessarily permanent and can change during critical periods like puberty or pregnancy.

Feeding pregnant mice a diet rich in methyl groups can alter the coat color of their offspring, indicating epigenetic changes.

Environmental toxins in the diet can lead to epigenetic changes that result in health issues like obesity in the next generation.

Epigenetic studies in humans, particularly identical twins, show that epigenetic differences can accumulate over time, especially with different lifestyles.

A study in Madrid aimed to determine the epigenetic similarities and differences among identical twins of various ages.

Epigenetic changes can be triggered by what we eat, smoke, or drink, potentially leading to diseases like cancer.

Cancer can be viewed as a disease stemming from epigenetic changes rather than solely from broken genes.

Epigenetic therapy is a new approach that aims to change the behavior of cancer cells by reactivating genes, rather than killing the cells.

Clinical trials using epigenetic therapy have shown promising results, with many patients achieving remission.

While it may be easier to fix our epigenome than our genome, it is also easier to mess it up, highlighting the importance of lifestyle choices.

Individuals have a responsibility for their epigenome, which can potentially be altered and impact future generations.

Epigenetic changes offer hope for disease prevention and treatment, as they are more malleable than genetic changes.

Transcripts

you ever noticed that if you get to know

two identical twins they might look

alike but they're always subtly

different yeah whatever as they get

older those differences can get more

pronounced two people start out the same

but their appearance and their health

can diverge for instance you have more

gray hair no no I don't identical twins

have the same DNA the exact same genes

yeah and don't our genes make us who we

are well they do yes but they're not the

whole story some researchers have

discovered a new bit of biology that can

work with our genes or against them yeah

you're heavier and I'm better looking

yeah

whatever imagine coming into the world

with a person so like yourself that for

a time you don't understand

mirrors as a child when I looked in the

mirror i' say that's my sister

and my mother will say no that's your

reflection and even if you resist this

cookie cutter

existence cultivate individual Styles

and abilities like cutting your hair

differently or running

faster uncanny similarities Bond you

together facial

expressions body

language the way you

laugh or dress for an interview perhaps

when you hadn't a clue what your sister

was going to wear

go the synchrony in your lives

constantly confronts

[Music]

you when I see my sister I see myself if

she looks good I think I look pretty

today but she's not wearing makeup I say

my God I look

horrible it's hardly surprising because

you both come from the same egg you have

precisely the same

jeans and you're literally

clones better known as identical

twins but now imagine

this one day your twin your clone is

diagnosed with

cancer if you're the other twin what can

you do except wait for the symptoms

I have been told that I am a high risk

for

cancer HS over

me and yet it's not uncommon for a twin

like Anna Marie to get a dread disease

while the other like clotilde

doesn't but how can two people so alike

be so unalike

well these mice May hold a

clue their DNA is as identical as Anam

Marie and clotilde's despite the

differences in their color and

[Music]

size the human who studies them is Duke

University's Randy

jle So Randy I see here you have skinny

mice and fat mice what have you done in

this lab well these animals are actually

genetically identical the fat ones and

the skinny ones that's correct cuz these

are huge they're huge can we weigh them

to find out so if you take this is looks

like they can barely walk they they

can't walk too much they're not going to

be running very far so that's about 63 G

63 G let's look at the other

one so it's half the weight right this

gets even more mysterious when you

realize that these identical mice both

have a particular Gene called ay but in

the yellow Mouse it stays on all the

time causing

obesity just look at

this so what accounts for the thin Mouse

exercise

Atkins no a tiny chemical tag of carbon

and hydrogen called a methyl group has a

fixed to the AI Gene shutting it

down creatures possess millions of tags

like

these some like methyl groups attach to

genes directly inhibiting their

function other types grab the proteins

called histones around which genes coil

and tighten or loosen them to control

gene

expression distinct methylation and

histone patterns exist in every cell

constituting a sort of second

genome The epig

genome

epigenetics literally translates into

just meaning above the genome so if you

would think for example of the genome as

being like a computer the hardware of

the of of a computer The epig genome

would be like the software that tells

the computer when to work how to work

and how

much in fact it's the EP genome that

tells our cells what sort of cells they

should be skin Hair Heart

you see all these cells have the same

genes but their epigenomes silence the

unneeded ones to make cells different

from one another epigenetic instructions

pass on as cells divide but they're not

necessarily permanent researchers think

they can change especially during

critical periods like puberty or

pregnancy jles mice reveal how the

epigenome can be

altered to produce thin Brown mice

instead of fat yellow ones he feeds

pregnant mothers a diet rich in methyl

groups to form the tags that can turn

genes

[Music]

off and I think you can

see that we dramatically shifted the

coat color and we get many many more

Brown animals and that matters because

your coat color is a tracer it's it's an

indicator that's correct of the the fact

that you have turned off that Gene

that's

right this epigenetic fix was also

inherited by the next generation of mice

regardless of what their mothers

ate and when an environmental toxin was

added to the diet instead of nutrients

more yellow babies were born doomed to

grow fat and sick like their

mothers it seems to me this has profound

implications for our health it does for

human health if there are genes like

this in humans basically what you eat

can affect your future Generations so

you're not only what you eat potentially

what your mother ate and possibly even

what your grandparents ate so how do you

go to humans to do this experiment when

you have these mice and they're

genetically identical on purpose that's

right who is your perfect Lab

human well then we look for identical

humans which are identical twins

[Music]

twins and that brings us to the reason

why were showing you Spanish

twins in 2005 they participated in a

groundbreaking study in

Madrid its aim to show just how

identical epigenetically they are or

aren't one of the question of twins is

that if my twin has this disease I will

have the same disease and genetics tell

us that there is a high risk of

developing the same disease but it's not

really sure they're going to have it

because our genes are just part of the

story something has to regulate these

genes and part of the explanation is

epigenetics estellar wanted to see if

the twins epigenomes might account for

their

differences to find out he and his team

collected cells from 40 pairs of

identical twins Age 3 to

[Music]

74 then began the laborious process of

dissolving the cells until all that was

left were wispy strands of DNA the

master molecule that contains our

[Music]

genes next researchers Amplified

fragments of the DNA until the genes

themselves became

detectable those that had been turned

off epigenetically appear as dark pink

bands on the

gel now notice what happens when the

genes from a pair of twins are cut out

and

overlapped the results are far from

subtle especially when you compare the

epigenomes of two sets of twins that

differ in

[Music]

age here on the left is the overla DNA

of 6-year-old Javier and

Carlos the yellow indicates where their

gene expression is

identical on the right is the DNA of

66-year-old anamarie and

clotilde in contrast to the younger

twins hardly any yellow shines

through their epigenomes have changed

dramatically the study suggests that as

Twins age epigenetic differences

accumulate especially when their

Lifestyles

differ one of the main findings of our

research is that episomes can change in

function of what we eat of what we smoke

or what we drink and this is one of the

key uh difference between epigenetics

and

genetics as the chemical tags that

control our genes

change cells can become abnormal

triggering diseases like

cancer take a disorder like MDS cancer

of the blood and bone

marrow it's not a diagnosis you'd ever

want to hear

when I went in then he started patting

my hand and he was going your blood work

does not look very good at all and that

I had um MDS leukemia and uh that there

was not a cure for it and basically I

had 6 months uh to live Char

coar was epigenetics the reason could

the silencing of critical genes turn

normal cells into cancerous

ones it's scary to think that a few

misplaced tags can kill

you but it's also good news because

we've traditionally viewed cancer as a

disease stemming solely from broken

genes and it's a lot harder to fix

damaged genes than to rearrange

epigenetic

tags in fact we already have a few drugs

that will

work recently Sandra Shelby and Roy

kwell participated in one of the first

clinical trials using epigenetic

therapy the idea of epigenetic therapy

is to stay away from killing the cell

rather what we are trying to do is

diplomacy trying to change the

instructions of the cancer cells

reminding the cell hey you're a human

cell you shouldn't be behaving this way

and we try to do that by reactivating

genes the results have been incredible

and I didn't have really any horrible

side

effects I am in

remission and going in the plus

direction is a whole lot better than the

minus

Direction in fact half the patients in

the trial are now in

[Music]

remission but while it may be easier to

fix our epigenome than our

genome messing it up is easier

too we've got to get people thinking

more about what they do they have a

responsibility for their epig genome

their genome they inherit but their epig

genome they potentially can alter and

particularly that of their children and

that brings in responsibility but it

also brings in hope you're not

necessarily stuck with this you can

alter this