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Do defects amplify in a self-replicating
self-correcting & self-maintaining machine
Do defects amplify in a self-replicating
self-correcting & self-maintaining machine
« As long as they
are
mortals, human
beings won't be
totally relaxed»
Woody Allen
Survival curves improved drastically since the XVIII century
Riley, Rising life expectancy
As all phenotypes, survival depends on
genotype and environment and …
Garsin, Science Juin 2003
Since the 18th century, life expectancy increased at all ages
Riley, Rising life expectancy
After childhood mortality,
mortality grows exponentially
with age (gompertz law)
Caleb Finch
Stress & age have multiplicative effects !
Caleb Finch
1
france
1000
,1
medical cost
death rate f rench woman 94
Both death rate and medical cost grow exponentially with age
,01
1E-3
1E-4
100
10
0
20
40
age
60
80
100
0
10
20
30
40
50
60
70
age
Thus understanding the mechanisms of exponential aging
should have huge public health and economic consequences
80
90
100
Mortality increases fast with too rich diets
Mair Sept 2003, Science
it is never too late…
improving the environment increases lifespan at old age
Vaupel, 2003, Science
A general trend:
mortality
first grows
exponentially
and then slower
aging projects
• Follow individuals throughout life span and look for
markers associated with timing of death
• Analyse mutants leading to faster/slower death
analysing the whole distribution of mortality patterns
• Develop rapid feedback between
modelling & experiments to test hypothesis
Test other model systems to look for general scenarii
Trade-off between life span and number of offsprings
Bacteriophages
180
12
Log (offspring/hour)
Number of offspring (log scale)
Mammals
100
50
20
15
10
0
10
8
6
4
2
0
10
20
30
40
50
lifespan (years)
From R. Holliday, Understanding
ageing, 1994
60
70
80
0
0
10
20
lifespan (days)
30
40
Main evolutionary transitions
J. Maynard-Smith & E. Szathmary
Prebiotic chemistry -------> Autocatalytic Replication
Self-replicated molecules -------> cell
Cell -------> multicellular organism
Organism -------> Society
Innate individual behavior -------> culture
Each transition is associated with a « conflict » between replicators
Co-evolution lead to interaction of organisms of interests that
• Diverge (competition, predator/prey, host/parasites) red queen & arm races
• Converge (cooperation, mutualism)
John Maynard Smith developped evolutionary game theory
to study their instability due to short term benefit of cheaters
Dangerous liaisons
Transition from one to the other via
environmental change
Mutation
Time-scales of biological dynamics
Molecular << life span < < ecological << evolution
The coevolving replicators can have different time scales
Conflicts between replicators as
causes of individuals death
•
•
•
•
Molecules vs cellule eg prion, aggregate
Cellular vs multi-cellular eg cancer
Individual vs society eg nihilism, wars
Idea vs individual eg suicide
Main causes of deaths today
• infectious diseases and hunger (3rd world)
• aging related disease (cancer, neurodegeneration)
• behaviorally associated causes:
suicide, wars, accidents, tobacco, alcool, drugs…
Junk food
our genomes have evolved in lack of food, sugar, animal fat, salt
these tendencies are used by food/marketing industry
the current world wide epidemic of obesity could
decrease life expectancy by 9 years.
Prevention is generally easier/cheapier than curing
“We humans are the only
species endowed with the
capacity to rebel against
the tyranny of our selfish
genes”
Richard Dawkins
“The Selfish Gene” 1976
Cigarettes & cancer
Cairns, matters of life and death
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Cancer incidence versus the number of
active p53 genes
(1) No active p53 genes is catastrophic (p53-/mice).
(1) (2) One p53 gene is better but still too
many cancers too early.
(1) (3) Two p53 gen es (normal mice and
humans): could be better.
(1) (4) Three or fou r p53 genes (mice): cancer
is much reduced
Piccinini 2002
Japan
80
70
Life Expectancy Trends: Paleolithic On
USA
60
Russia
50
40
30
Paleolithic
S u b -S a h a r a n
A f r ic a
Rome
20
Present
(1990)
(1900)
1000
10000
100,000
Ye a r s b e f o r e p re s e n t ( l o g sc a le )
Courbe de survie chez les chasseurs-cueilleurs
L’espérance de vie décroît à Rome…
(les épidémies sont favorisées par la fréquence des contacts)
L’espérance de vie croît dès le 18e siècle…
Life expectancy still grows steadily & linearly
Oepen, Science 2002
Gompertz law : mortality rate double every 8 years
death rate f rench woman 1994
1
10-1
10-2
10-3
10-4
0
20
40
age
60
80
100
Tuberculosis : environment before medicine ?!
Cairns, matters of life and death
Tuberculose : effet modéré des antibiotiques ?!
Being rich helps but is not the only secret to long life
Mieux vaut être riche et en bonne santé !?
Effet de l’éducation sur la survie
Cairns, matters of life and death
Interdisciplinary approaches of bacterial variability
Who changes ?
Molecular epidemiology
Why change ?
Population genetics
Binguen Denamur Picard Brisabois Berche
Godelle Gouyon Brown Maynard-Smith
B. Toupance
O. Tenaillon
J-B André
Change what?
Bio-informatics
Rocha
Change where ?
Microbial ecology
Fons
Duriez
How to change ?
Molecular biology
Matic Radman Vulic Dionisio Bjedov
Bregeon Leroy Hayakawa Sekiguchi Dukan
Who has changed ?
Molecular Phylogeny
Lecointre Darlu
Giraud
Lechat
Bambou
Change when ?
transcriptome analysis
Knudsen Cerf
Phenotypic variability & aging
Life History
Stewart Madden Lindner
Paul Gabriel Fontaine
Depaepe Bredèche Mosse r Diard
Propagation des idées et des techniques
(progrès technologiques, scientifiques, médicaux et communication)
QuickTime™ et un décompresseur
Photo - JPEG sont requis pour visualiser
cette image.
van Leeuwenhoek