Fetal programming

1

5

3

2

Ontogenesis Phylogenesis

Developmental Plasticity

Devo-Evo 4

MismatchDOHA 6

7

XX Century Epidemiological

Transition

Environment

From Genetics to Epigenetics

Epigenetic versus genetic origins of health and diseases the 7 key words

Evolutionary Medicine

Is DNA a sort of Project inscribed in our cells

ERNESTO BURGIO ISDE Scientific Committee ECERI - European Cancer and Environment Research Institute

Insulino-resistance

Diabetes

Cardiovascular Diseases

The XXth Century Epidemiological transition

hellip from a prevalence of acute exogenous (infectious and parasitic)

to a prevalence of chronic endogenous diseases (immunological

neurodegenerative neuro-endocrine cardiovascular and neoplastic)

Barker Hypothesis (1989)

(1989)

a b

c

Letrsquos begin by the seventh key word

ENVIRONMENTAL FACTORS gtgt DNA

TIPE I DIABETES

X 10

amp Non-

Communicable

Diseases

The Obesity

and Diabesity Pandemics

For the first time in human history the number of overweight people rivals the number of underweight peoplehellip While the worldrsquos underfed population has slightly declined since 1980 to 11 billion the number of overweight people has surged to 11 billion

Chronic Hunger and Obesity Epidemic Eroding Global Progress

Obesity Trends Among US Adults 1985

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1987

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1993

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Insulino-resistance

Diabetes

Cardiovascular Diseases

The XXth Century Epidemiological transition

hellip from a prevalence of acute exogenous (infectious and parasitic)

to a prevalence of chronic endogenous diseases (immunological

neurodegenerative neuro-endocrine cardiovascular and neoplastic)

Barker Hypothesis (1989)

(1989)

a b

c

Letrsquos begin by the seventh key word

ENVIRONMENTAL FACTORS gtgt DNA

TIPE I DIABETES

X 10

amp Non-

Communicable

Diseases

The Obesity

and Diabesity Pandemics

For the first time in human history the number of overweight people rivals the number of underweight peoplehellip While the worldrsquos underfed population has slightly declined since 1980 to 11 billion the number of overweight people has surged to 11 billion

Chronic Hunger and Obesity Epidemic Eroding Global Progress

Obesity Trends Among US Adults 1985

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1987

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1993

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

ENVIRONMENTAL FACTORS gtgt DNA

TIPE I DIABETES

X 10

amp Non-

Communicable

Diseases

The Obesity

and Diabesity Pandemics

For the first time in human history the number of overweight people rivals the number of underweight peoplehellip While the worldrsquos underfed population has slightly declined since 1980 to 11 billion the number of overweight people has surged to 11 billion

Chronic Hunger and Obesity Epidemic Eroding Global Progress

Obesity Trends Among US Adults 1985

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1987

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1993

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

The Obesity

and Diabesity Pandemics

For the first time in human history the number of overweight people rivals the number of underweight peoplehellip While the worldrsquos underfed population has slightly declined since 1980 to 11 billion the number of overweight people has surged to 11 billion

Chronic Hunger and Obesity Epidemic Eroding Global Progress

Obesity Trends Among US Adults 1985

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1987

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1993

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Obesity Trends Among US Adults 1985

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1987

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1993

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Obesity Trends Among US Adults 1987

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1993

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Obesity Trends Among US Adults 1993

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Obesity Trends Among US Adults 1995

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Obesity Trends Among US Adults 1997

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Obesity Trends Among US Adults 1999

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Obesity Trends Among US Adults 2001

Source Mokdad A H et al J Am Med Assoc 199928216 200128610

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

The Childhood Obesity Epidemic

US DHHS 2001 Hedley et al 2004 Ogden et al 2006 2008

Matthew W Gillman MD SM

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

The main difference between the two large

epidemics of malnutrition even symbolically

opposite concerning half of the inhabitants

of the planet is that

-while malnutrition is the effect

of an economic and political

unbalanced and unfair situation

-the pandemic of obesity and diabesity

advancing all over the planet that could

transform into a kind of tsunami able to

disintegrate the public health systems

of the northern hemisphere is a symptom

of a evolutionary dis-adaptation or a

rapidly progressive misprogramming of

the entire endocrine-metabolic (central

hypothalamic and peripheral) which should

regulate income and energy consumption

induced by environmental and

nutritional dramatic transformations

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Many scientists and researchers claim that Autism is

the fastest-growing developmental disorder in the world

with the prevalence of diagnosis having increased

by 600 per cent over the last 20 years And from

11200 to 190 children in US in the last 30 years

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

Such comparisons show large recent increases in rates of autism and autistic

spectrum disorders in both the US and the UK

Reported rates of autism in the US increased from lt 3 per 10000 children in the

1970s to gt 30 per 10000 children in the 1990s a 10-fold increase

In the United Kingdom autism rates rose from lt 10 per 10000 in the 1980s

to roughly 30 per 10000 in the 1990s

Reported rates for the full spectrum of autistic disorders rose from the 5 to 10

per 10000 range to the 50 to 80 per 10000 range in the two countries (1150-200)

Blaxill MF Whats going on The question of time trends in

autism Public Health Rep 2004 119(6)536-51

AUTISME (ASD Autism Spectrum Disorders)

bullNew diagnosed cases of autism (incidence) in US

increased from 15580 in 1992 to 163773 in 2003

bull Estimated prevalence 6-7-12 cases1000 children (2012)

Alzheimer_and_other_dementias_world_map_-_DALY_-_WHO2004_svg

In 1997 the prevalence in the US was 232 million

Increased amyloid

A-deposition

Accumulation of hyperphosphorylated

microtubule associated protein ldquotanglesrdquo

(LEARn) model early environmental factors such as

exposure to Pb nutritional deficiencies (eg folate or

B12) or oxidative stress alter DNA epigenetically by

reducing the activity of enzymes as DNMTshellip

Deaths from urban air pollution in 2000 as estimated by the WHO

World Health Report 2002

The WHO estimates that air pollution is responsible

for 3 million premature deaths each year

No one likes to talk about a CANCER PANDEMIC But we must

not forget that today practically all over the North of the world

one person out of two is likely to have a cancer

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

Th

ou

sa

nd

s p

er

An

nu

m

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

the significant increase in the Less Developed Countries amp in young people all over

the world demonstrates the limits of the SMT (necessary link between aging ampCA)

Increased amyloid

A-deposition

Accumulation of hyperphosphorylated

microtubule associated protein ldquotanglesrdquo

(LEARn) model early environmental factors such as

exposure to Pb nutritional deficiencies (eg folate or

B12) or oxidative stress alter DNA epigenetically by

reducing the activity of enzymes as DNMTshellip

Deaths from urban air pollution in 2000 as estimated by the WHO

World Health Report 2002

The WHO estimates that air pollution is responsible

for 3 million premature deaths each year

No one likes to talk about a CANCER PANDEMIC But we must

not forget that today practically all over the North of the world

one person out of two is likely to have a cancer

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

Th

ou

sa

nd

s p

er

An

nu

m

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

the significant increase in the Less Developed Countries amp in young people all over

the world demonstrates the limits of the SMT (necessary link between aging ampCA)

Deaths from urban air pollution in 2000 as estimated by the WHO

World Health Report 2002

The WHO estimates that air pollution is responsible

for 3 million premature deaths each year

No one likes to talk about a CANCER PANDEMIC But we must

not forget that today practically all over the North of the world

one person out of two is likely to have a cancer

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

Th

ou

sa

nd

s p

er

An

nu

m

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

the significant increase in the Less Developed Countries amp in young people all over

the world demonstrates the limits of the SMT (necessary link between aging ampCA)

No one likes to talk about a CANCER PANDEMIC But we must

not forget that today practically all over the North of the world

one person out of two is likely to have a cancer

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

Th

ou

sa

nd

s p

er

An

nu

m

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

the significant increase in the Less Developed Countries amp in young people all over

the world demonstrates the limits of the SMT (necessary link between aging ampCA)

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

Th

ou

sa

nd

s p

er

An

nu

m

0

2000

4000

6000

8000

10000

12000

14000

2002 2005 2010 2015 2020

Less Developed More Developed

the significant increase in the Less Developed Countries amp in young people all over

the world demonstrates the limits of the SMT (necessary link between aging ampCA)

Cancer incidence in childhood and adolescence - EUROPE ( 1970-1999)

mother

latency

A first draft of the report published on the Lancet in 2004 demonstrates an annual increase of 1-15 for all cancers (with more marked increases in lymphomas soft tissue sarcomas tumors of the nervous systemhellip)

As we may easily argue from the recent project ACCIS (Automated Childhood Cancer Information System) - a comprehensive monitoring conducted by a team of epidemiologists IARC on 63 cancer registries from 19 European countries for a total of over 130 thousand tumors of all types (113 thousand children and 18 thousand teenagers)

Steliarova-Foucher E Stiller C Kaatsch P Berrino F Coebergh JW Lacour B Parkin M Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCISproject) an epidemiological study Lancet 2004 Dec 11-17364(9451)2097-105

httpwww-depiarcfraccishtm

Fetal programming

1

5

3

2

Ontogenesis Phylogenesis

Developmental Plasticity

Devo-Evo

4

MismatchDOHA 6

7 XX Century

Epidemiologic Transition

Environment

From Genetics to Epigenetics

Epigenetic versus genetic origins of

health and diseases the 7 key words Evolutionary Medicine

Is DNA a sort of Project inscribed in our cells

At this pointhaving quickly mapped out

the dramatic epidemiological transition

underway we can briefly examine the other

6 key words

Interphase chromosomes

Mitotic chromosome

Euchromatin

Heterochromatin

revolving

around it and

playing an

important role

in

transferring

information

from outside

to DNA and

in

modulating

the

response to

the extent

that some

scientists

have used

the term

natural

genetic

engineering

The first keyword Epigenetics

Multiple levels of packing are required to fit the DNA into the cell nucleus

Rudolf Jaenisch Whitehead Institute amp Dept of Biology MIT Cambridge MA

Nuclear Receptor DNA Response Element

Histone Lysine Acetylation

Histone Deacetylases

Histone Acetyltransferases

Histone Methyltransferases

ATP-dependent Nucleosome Remodeling Complex

Many toxicants cause rapid alterations in gene expression by activating protein kinase signaling

cascades

The resulting rapid defensive alterations in

gene activity require the transmission of a signal directly to the histones

present in the chromatin of stress response genes

within minutes

of exposure the phosphorylation of serine 10 of histone H3

and the acetylation

of lysines 9 andor 14 take place

H3-K9 H3-S10

P

The ldquomeeting-pointrdquo between the information coming from the environment and the information encoded in the DNA (hardware) is the epigenome (software) mimetic molecules (EDCs) and other pollutants or danger-signals induce the epigenome to change

Chromatin itself is the direct target of many toxicants hellip toxicant-induced perturbations in chromatin structure may precipitate adverse effects Forcing genome to change

In 1997 the well known molecular biologist R Strohman attempted an oblique attack against the central dogma of molecular biology the deterministic linear uni-directional and encapsulated path from DNA to RNA to proteins to phenotype

We have

wrongly

extended the

linear theory of

the gene to the

ldquorealmrdquo

of the gene

management

but the gene

management is

an entirely

different

process

involving

interactive

cellular

processes that

display an

interactive

complexityhellip

which is

epigenetic in

nature 1

2

3

Towards a Kuhnian Revolution in Biology and Cancer Research

httpnewssciencemagorgsciencenow20090421-03html

IN FACT Genes need to be told to switch ldquooffrdquo and ldquoonrdquo bull Genes need to be told how much expression (protein) is required and where bull Genes need to be regulated ndash this regulation is not performed by DNA but by many other controls arranged in a complex network bull DNA has been called the Book of Life by the Human Genome Project scientists but many other biologists consider DNA to be simply a random collection of words from which a meaningful story of life may be assembledhellip bull In order to assemble that meaningful story a living cell uses a second informational system () The key concept here is that these dynamic-epigenetic networks have a life of their own mdashthey follow network-rules not specified by DNA

From directing the fate of stem cells to determining how we grow the genes in our body act in complex networks the whole Genome is a Complex and highly dynamic molecular Network of interacting Genes and non-codifying sequences and proteins

Strohman R April 2001 Beyond genetic determinism hellipGenes Know How to NetworkhellipBUT

Aujourdhui nous savons que le geacutenome est un reacuteseau moleacuteculaire unique complexe et dynamique et quil ya un flux ininterrompu dinformations au sein du geacutenome et entre le geacutenome et lenvironnement

DNA double helix (2-nm diameter)

Metaphase chromosome 700 nm

Tight helical fiber (30-nm diameter)

Nucleosome (10-nm diameter)

Histones

ldquoBeads on a stringrdquo

Supercoil (200-nm diameter)

Campbell NE et al (Eds) Biology Concepts amp Connections 4th Edition 2003

Euchromatin

Heterochromatin

Multiple levels of packing are required to fit the DNA into the cell nucleus

Nuclear DNA is normally tightly wrapped around histones

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

Interphase chromosomes

Mitotic chromosome

Euchromatin

Heterochromatin

revolving

around it and

playing an

important role

in

transferring

information

from outside

to DNA and

in

modulating

the

response to

the extent

that some

scientists

have used

the term

natural

genetic

engineering

The first keyword Epigenetics

Multiple levels of packing are required to fit the DNA into the cell nucleus

Rudolf Jaenisch Whitehead Institute amp Dept of Biology MIT Cambridge MA

Nuclear Receptor DNA Response Element

Histone Lysine Acetylation

Histone Deacetylases

Histone Acetyltransferases

Histone Methyltransferases

ATP-dependent Nucleosome Remodeling Complex

Many toxicants cause rapid alterations in gene expression by activating protein kinase signaling

cascades

The resulting rapid defensive alterations in

gene activity require the transmission of a signal directly to the histones

present in the chromatin of stress response genes

within minutes

of exposure the phosphorylation of serine 10 of histone H3

and the acetylation

of lysines 9 andor 14 take place

H3-K9 H3-S10

P

The ldquomeeting-pointrdquo between the information coming from the environment and the information encoded in the DNA (hardware) is the epigenome (software) mimetic molecules (EDCs) and other pollutants or danger-signals induce the epigenome to change

Chromatin itself is the direct target of many toxicants hellip toxicant-induced perturbations in chromatin structure may precipitate adverse effects Forcing genome to change

In 1997 the well known molecular biologist R Strohman attempted an oblique attack against the central dogma of molecular biology the deterministic linear uni-directional and encapsulated path from DNA to RNA to proteins to phenotype

We have

wrongly

extended the

linear theory of

the gene to the

ldquorealmrdquo

of the gene

management

but the gene

management is

an entirely

different

process

involving

interactive

cellular

processes that

display an

interactive

complexityhellip

which is

epigenetic in

nature 1

2

3

Towards a Kuhnian Revolution in Biology and Cancer Research

httpnewssciencemagorgsciencenow20090421-03html

IN FACT Genes need to be told to switch ldquooffrdquo and ldquoonrdquo bull Genes need to be told how much expression (protein) is required and where bull Genes need to be regulated ndash this regulation is not performed by DNA but by many other controls arranged in a complex network bull DNA has been called the Book of Life by the Human Genome Project scientists but many other biologists consider DNA to be simply a random collection of words from which a meaningful story of life may be assembledhellip bull In order to assemble that meaningful story a living cell uses a second informational system () The key concept here is that these dynamic-epigenetic networks have a life of their own mdashthey follow network-rules not specified by DNA

From directing the fate of stem cells to determining how we grow the genes in our body act in complex networks the whole Genome is a Complex and highly dynamic molecular Network of interacting Genes and non-codifying sequences and proteins

Strohman R April 2001 Beyond genetic determinism hellipGenes Know How to NetworkhellipBUT

Aujourdhui nous savons que le geacutenome est un reacuteseau moleacuteculaire unique complexe et dynamique et quil ya un flux ininterrompu dinformations au sein du geacutenome et entre le geacutenome et lenvironnement

DNA double helix (2-nm diameter)

Metaphase chromosome 700 nm

Tight helical fiber (30-nm diameter)

Nucleosome (10-nm diameter)

Histones

ldquoBeads on a stringrdquo

Supercoil (200-nm diameter)

Campbell NE et al (Eds) Biology Concepts amp Connections 4th Edition 2003

Euchromatin

Heterochromatin

Multiple levels of packing are required to fit the DNA into the cell nucleus

Nuclear DNA is normally tightly wrapped around histones

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

Rudolf Jaenisch Whitehead Institute amp Dept of Biology MIT Cambridge MA

Nuclear Receptor DNA Response Element

Histone Lysine Acetylation

Histone Deacetylases

Histone Acetyltransferases

Histone Methyltransferases

ATP-dependent Nucleosome Remodeling Complex

Many toxicants cause rapid alterations in gene expression by activating protein kinase signaling

cascades

The resulting rapid defensive alterations in

gene activity require the transmission of a signal directly to the histones

present in the chromatin of stress response genes

within minutes

of exposure the phosphorylation of serine 10 of histone H3

and the acetylation

of lysines 9 andor 14 take place

H3-K9 H3-S10

P

The ldquomeeting-pointrdquo between the information coming from the environment and the information encoded in the DNA (hardware) is the epigenome (software) mimetic molecules (EDCs) and other pollutants or danger-signals induce the epigenome to change

Chromatin itself is the direct target of many toxicants hellip toxicant-induced perturbations in chromatin structure may precipitate adverse effects Forcing genome to change

In 1997 the well known molecular biologist R Strohman attempted an oblique attack against the central dogma of molecular biology the deterministic linear uni-directional and encapsulated path from DNA to RNA to proteins to phenotype

We have

wrongly

extended the

linear theory of

the gene to the

ldquorealmrdquo

of the gene

management

but the gene

management is

an entirely

different

process

involving

interactive

cellular

processes that

display an

interactive

complexityhellip

which is

epigenetic in

nature 1

2

3

Towards a Kuhnian Revolution in Biology and Cancer Research

httpnewssciencemagorgsciencenow20090421-03html

IN FACT Genes need to be told to switch ldquooffrdquo and ldquoonrdquo bull Genes need to be told how much expression (protein) is required and where bull Genes need to be regulated ndash this regulation is not performed by DNA but by many other controls arranged in a complex network bull DNA has been called the Book of Life by the Human Genome Project scientists but many other biologists consider DNA to be simply a random collection of words from which a meaningful story of life may be assembledhellip bull In order to assemble that meaningful story a living cell uses a second informational system () The key concept here is that these dynamic-epigenetic networks have a life of their own mdashthey follow network-rules not specified by DNA

From directing the fate of stem cells to determining how we grow the genes in our body act in complex networks the whole Genome is a Complex and highly dynamic molecular Network of interacting Genes and non-codifying sequences and proteins

Strohman R April 2001 Beyond genetic determinism hellipGenes Know How to NetworkhellipBUT

Aujourdhui nous savons que le geacutenome est un reacuteseau moleacuteculaire unique complexe et dynamique et quil ya un flux ininterrompu dinformations au sein du geacutenome et entre le geacutenome et lenvironnement

DNA double helix (2-nm diameter)

Metaphase chromosome 700 nm

Tight helical fiber (30-nm diameter)

Nucleosome (10-nm diameter)

Histones

ldquoBeads on a stringrdquo

Supercoil (200-nm diameter)

Campbell NE et al (Eds) Biology Concepts amp Connections 4th Edition 2003

Euchromatin

Heterochromatin

Multiple levels of packing are required to fit the DNA into the cell nucleus

Nuclear DNA is normally tightly wrapped around histones

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

Nuclear Receptor DNA Response Element

Histone Lysine Acetylation

Histone Deacetylases

Histone Acetyltransferases

Histone Methyltransferases

ATP-dependent Nucleosome Remodeling Complex

Many toxicants cause rapid alterations in gene expression by activating protein kinase signaling

cascades

The resulting rapid defensive alterations in

gene activity require the transmission of a signal directly to the histones

present in the chromatin of stress response genes

within minutes

of exposure the phosphorylation of serine 10 of histone H3

and the acetylation

of lysines 9 andor 14 take place

H3-K9 H3-S10

P

The ldquomeeting-pointrdquo between the information coming from the environment and the information encoded in the DNA (hardware) is the epigenome (software) mimetic molecules (EDCs) and other pollutants or danger-signals induce the epigenome to change

Chromatin itself is the direct target of many toxicants hellip toxicant-induced perturbations in chromatin structure may precipitate adverse effects Forcing genome to change

In 1997 the well known molecular biologist R Strohman attempted an oblique attack against the central dogma of molecular biology the deterministic linear uni-directional and encapsulated path from DNA to RNA to proteins to phenotype

We have

wrongly

extended the

linear theory of

the gene to the

ldquorealmrdquo

of the gene

management

but the gene

management is

an entirely

different

process

involving

interactive

cellular

processes that

display an

interactive

complexityhellip

which is

epigenetic in

nature 1

2

3

Towards a Kuhnian Revolution in Biology and Cancer Research

httpnewssciencemagorgsciencenow20090421-03html

IN FACT Genes need to be told to switch ldquooffrdquo and ldquoonrdquo bull Genes need to be told how much expression (protein) is required and where bull Genes need to be regulated ndash this regulation is not performed by DNA but by many other controls arranged in a complex network bull DNA has been called the Book of Life by the Human Genome Project scientists but many other biologists consider DNA to be simply a random collection of words from which a meaningful story of life may be assembledhellip bull In order to assemble that meaningful story a living cell uses a second informational system () The key concept here is that these dynamic-epigenetic networks have a life of their own mdashthey follow network-rules not specified by DNA

From directing the fate of stem cells to determining how we grow the genes in our body act in complex networks the whole Genome is a Complex and highly dynamic molecular Network of interacting Genes and non-codifying sequences and proteins

Strohman R April 2001 Beyond genetic determinism hellipGenes Know How to NetworkhellipBUT

Aujourdhui nous savons que le geacutenome est un reacuteseau moleacuteculaire unique complexe et dynamique et quil ya un flux ininterrompu dinformations au sein du geacutenome et entre le geacutenome et lenvironnement

DNA double helix (2-nm diameter)

Metaphase chromosome 700 nm

Tight helical fiber (30-nm diameter)

Nucleosome (10-nm diameter)

Histones

ldquoBeads on a stringrdquo

Supercoil (200-nm diameter)

Campbell NE et al (Eds) Biology Concepts amp Connections 4th Edition 2003

Euchromatin

Heterochromatin

Multiple levels of packing are required to fit the DNA into the cell nucleus

Nuclear DNA is normally tightly wrapped around histones

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

In 1997 the well known molecular biologist R Strohman attempted an oblique attack against the central dogma of molecular biology the deterministic linear uni-directional and encapsulated path from DNA to RNA to proteins to phenotype

We have

wrongly

extended the

linear theory of

the gene to the

ldquorealmrdquo

of the gene

management

but the gene

management is

an entirely

different

process

involving

interactive

cellular

processes that

display an

interactive

complexityhellip

which is

epigenetic in

nature 1

2

3

Towards a Kuhnian Revolution in Biology and Cancer Research

httpnewssciencemagorgsciencenow20090421-03html

IN FACT Genes need to be told to switch ldquooffrdquo and ldquoonrdquo bull Genes need to be told how much expression (protein) is required and where bull Genes need to be regulated ndash this regulation is not performed by DNA but by many other controls arranged in a complex network bull DNA has been called the Book of Life by the Human Genome Project scientists but many other biologists consider DNA to be simply a random collection of words from which a meaningful story of life may be assembledhellip bull In order to assemble that meaningful story a living cell uses a second informational system () The key concept here is that these dynamic-epigenetic networks have a life of their own mdashthey follow network-rules not specified by DNA

From directing the fate of stem cells to determining how we grow the genes in our body act in complex networks the whole Genome is a Complex and highly dynamic molecular Network of interacting Genes and non-codifying sequences and proteins

Strohman R April 2001 Beyond genetic determinism hellipGenes Know How to NetworkhellipBUT

Aujourdhui nous savons que le geacutenome est un reacuteseau moleacuteculaire unique complexe et dynamique et quil ya un flux ininterrompu dinformations au sein du geacutenome et entre le geacutenome et lenvironnement

DNA double helix (2-nm diameter)

Metaphase chromosome 700 nm

Tight helical fiber (30-nm diameter)

Nucleosome (10-nm diameter)

Histones

ldquoBeads on a stringrdquo

Supercoil (200-nm diameter)

Campbell NE et al (Eds) Biology Concepts amp Connections 4th Edition 2003

Euchromatin

Heterochromatin

Multiple levels of packing are required to fit the DNA into the cell nucleus

Nuclear DNA is normally tightly wrapped around histones

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

httpnewssciencemagorgsciencenow20090421-03html

IN FACT Genes need to be told to switch ldquooffrdquo and ldquoonrdquo bull Genes need to be told how much expression (protein) is required and where bull Genes need to be regulated ndash this regulation is not performed by DNA but by many other controls arranged in a complex network bull DNA has been called the Book of Life by the Human Genome Project scientists but many other biologists consider DNA to be simply a random collection of words from which a meaningful story of life may be assembledhellip bull In order to assemble that meaningful story a living cell uses a second informational system () The key concept here is that these dynamic-epigenetic networks have a life of their own mdashthey follow network-rules not specified by DNA

From directing the fate of stem cells to determining how we grow the genes in our body act in complex networks the whole Genome is a Complex and highly dynamic molecular Network of interacting Genes and non-codifying sequences and proteins

Strohman R April 2001 Beyond genetic determinism hellipGenes Know How to NetworkhellipBUT

Aujourdhui nous savons que le geacutenome est un reacuteseau moleacuteculaire unique complexe et dynamique et quil ya un flux ininterrompu dinformations au sein du geacutenome et entre le geacutenome et lenvironnement

DNA double helix (2-nm diameter)

Metaphase chromosome 700 nm

Tight helical fiber (30-nm diameter)

Nucleosome (10-nm diameter)

Histones

ldquoBeads on a stringrdquo

Supercoil (200-nm diameter)

Campbell NE et al (Eds) Biology Concepts amp Connections 4th Edition 2003

Euchromatin

Heterochromatin

Multiple levels of packing are required to fit the DNA into the cell nucleus

Nuclear DNA is normally tightly wrapped around histones

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

DNA double helix (2-nm diameter)

Metaphase chromosome 700 nm

Tight helical fiber (30-nm diameter)

Nucleosome (10-nm diameter)

Histones

ldquoBeads on a stringrdquo

Supercoil (200-nm diameter)

Campbell NE et al (Eds) Biology Concepts amp Connections 4th Edition 2003

Euchromatin

Heterochromatin

Multiple levels of packing are required to fit the DNA into the cell nucleus

Nuclear DNA is normally tightly wrapped around histones

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

The Epigenetic Players

DNA Methylation

Histone modification

Chromatin Remodeling machinery

+

ON OFF

Euchromatin

Heterochromatin

ldquoThe study of heritable changes in gene function that occur without a change in the DNA sequencerdquo

Fraga et al PNAS 2005

1

4

3 2

MicroRNAs

DNA methylation

Covalent modification of the DNA is also important for gene silencing human cells Most genes have GC rich areas of DNA in their promoter regions referred to as CpG islands Methylation of the C residues within the CpG islands leads to gene silencing

(highly unstable base)

2

The Histone tails are a critical determinant of chromatin structure

1

Histone Tails are subject to a variety of covalent modifications

Histone Coderdquo hypothesis modifications of the Histone tails act as marks read by other proteins to control the expression or replication of chromosomal regions

Eg generally Histone Acetylation is associated with transcriptionally active genes Deacetylation is associated with inactive genes (= gene silencing)

3

httpwwwgene-quantificationdemicro-rna-1htmlnature

TCDD

Viruses

HERVs

EMF

3

2

1

SYNERGISM

ldquoFLUID EPI-GENOMErdquo

4

We may represent the environment as a continuous stream of information (simple photons individual packages of E = M = Information) or complex (organic molecules viruses etc) interacting with our cells [membrane transmembrane receptors signal transduction proteins nuclear receptors genome (DNA + Epigenome)] forcing them to adapt

The second keyword Environment

The Histone tails are a critical determinant of chromatin structure

1

Histone Tails are subject to a variety of covalent modifications

Histone Coderdquo hypothesis modifications of the Histone tails act as marks read by other proteins to control the expression or replication of chromosomal regions

Eg generally Histone Acetylation is associated with transcriptionally active genes Deacetylation is associated with inactive genes (= gene silencing)

3

httpwwwgene-quantificationdemicro-rna-1htmlnature

TCDD

Viruses

HERVs

EMF

3

2

1

SYNERGISM

ldquoFLUID EPI-GENOMErdquo

4

We may represent the environment as a continuous stream of information (simple photons individual packages of E = M = Information) or complex (organic molecules viruses etc) interacting with our cells [membrane transmembrane receptors signal transduction proteins nuclear receptors genome (DNA + Epigenome)] forcing them to adapt

The second keyword Environment

Histone Tails are subject to a variety of covalent modifications

Histone Coderdquo hypothesis modifications of the Histone tails act as marks read by other proteins to control the expression or replication of chromosomal regions

Eg generally Histone Acetylation is associated with transcriptionally active genes Deacetylation is associated with inactive genes (= gene silencing)

3

httpwwwgene-quantificationdemicro-rna-1htmlnature

TCDD

Viruses

HERVs

EMF

3

2

1

SYNERGISM

ldquoFLUID EPI-GENOMErdquo

4

We may represent the environment as a continuous stream of information (simple photons individual packages of E = M = Information) or complex (organic molecules viruses etc) interacting with our cells [membrane transmembrane receptors signal transduction proteins nuclear receptors genome (DNA + Epigenome)] forcing them to adapt

The second keyword Environment

3

httpwwwgene-quantificationdemicro-rna-1htmlnature

TCDD

Viruses

HERVs

EMF

3

2

1

SYNERGISM

ldquoFLUID EPI-GENOMErdquo

4

We may represent the environment as a continuous stream of information (simple photons individual packages of E = M = Information) or complex (organic molecules viruses etc) interacting with our cells [membrane transmembrane receptors signal transduction proteins nuclear receptors genome (DNA + Epigenome)] forcing them to adapt

The second keyword Environment

TCDD

Viruses

HERVs

EMF

3

2

1

SYNERGISM

ldquoFLUID EPI-GENOMErdquo

4

We may represent the environment as a continuous stream of information (simple photons individual packages of E = M = Information) or complex (organic molecules viruses etc) interacting with our cells [membrane transmembrane receptors signal transduction proteins nuclear receptors genome (DNA + Epigenome)] forcing them to adapt

The second keyword Environment