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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 theyare
mortals, humanbeings won't betotally 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 exponentiallywith age (gompertz law)
Caleb Finch
Stress & age have multiplicative effects !
Caleb Finch
1E-4
1E-3
,01
,1
1
death
rate
f re
nch
w
om
an
94
0 20 40 60 80 100
age
10
100
1000
med
ical cost
f
ran
ce
0 10 20 30 40 50 60 70 80 90 100
age
Both death rate and medical cost grow exponentially with age
Thus understanding the mechanisms of exponential aging should have huge public health and economic consequences
Mortality increases fast with too rich diets
Mair Sept 2003, Science
Vaupel, 2003, Science
it is never too late… improving the environment increases lifespan at old age
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 betweenmodelling & experiments to test hypothesis
Test other model systems to look for general scenarii
Trade-off between life span and number of offsprings
180
lifespan (years)
Num
ber
of o
ffsp
ring
(lo
g s
cale
)
0 10 20 30 40 60 7050 80
100
50
20
15
10
0
From R. Holliday, Understanding ageing, 1994
Mammals
0
2
4
6
8
10
12
0 10 20 30 40
lifespan (days)
Bacteriophages
Log
(of
fspr
ing/
hour
)
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 liaisonsTransition from one to the other viaenvironmental changeMutation
Time-scales of biological dynamicsMolecular << 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, saltthese 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 onlyspecies endowed with thecapacity to rebel againstthe tyranny of our selfishgenes”
Richard Dawkins“The Selfish Gene” 1976
Cigarettes & cancer
Cairns, matters of life and death
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualisercette image.
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cette image.
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cette image.
Cancer incidence versus the number ofactive p53 genes
(1) No active p53 genes is catastrophic (p53-/-mice).
(1) (2) One p53 gene is better but still toomany cancers too early.
(1) (3) Two p53 gen es (normal mice andhumans): could be better.
(1) (4) Three or four p53 genes (mice): canceris much reduced
Piccinini 2002
S ub -S a ha ranA fr ica
Russia
Japan
USA
Rome
Paleolithic
20
30
50
60
70
80
40
Life Expectancy Trends: Paleolithic On
Present (1990) (1900) 1000 10000 100,000
Y e a r s b e f o r e p r e s e n t ( l o g s c a l e )
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
10-4
10-3
10-2
10-1
1
death
rate
f r
en
ch
w
om
an
1994
0 20 40 60 80 100
age
Gompertz law : mortality rate double every 8 years
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
Why change ?Population geneticsGodelle Gouyon Brown Maynard-Smith
Change where ?Microbial ecology Fons
Who changes ?Molecular epidemiologyBinguen Denamur Picard Brisabois Berche
Interdisciplinary approaches of bacterial variability
GiraudLechatBambou
B. ToupanceO. TenaillonJ-B André
Duriez
Change what?Bio-informaticsRocha
Who has changed ?Molecular PhylogenyLecointre Darlu
How to change ? Molecular biology Matic Radman Vulic Dionisio BjedovBregeon Leroy Hayakawa Sekiguchi Dukan
Change when ?transcriptome analysis Knudsen Cerf
Phenotypic variability & agingLife History Stewart Madden Lindner Paul Gabriel Fontaine Depaepe Bredèche Mosse r Diard
QuickTime™ et un décompresseurPhoto - JPEG sont requis pour visualiser
cette image.
Propagation des idées et des techniques(progrès technologiques, scientifiques, médicaux et communication)
van Leeuwenhoek
