Do defects amplify in a self-replicating self-correcting & self-maintaining machine

1. Do defects amplify in a self-replicating self-correcting & self-maintaining machine

2. Do defects amplify in a self-replicating self-correcting & self-maintaining machine

4. Survival curves improved drastically since the XVIII century Riley, Rising life expectancy

5. As all phenotypes,survival depends on genotype and environment and … Garsin, Science Juin 2003

6. Since the 18th century, life expectancy increased at all ages Riley, Rising life expectancy

7. After childhood mortality, mortality grows exponentially with age (gompertz law) Caleb Finch

8. Stress & age have multiplicative effects ! Caleb Finch

9. Both death rate and medical cost grow exponentially with age 1 1000 ,1 death rate f rench woman 94 medical cost france ,01 100 1E-3 1E-4 10 0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100 age age Thus understanding the mechanisms of exponential aging should have huge public health and economic consequences

10. Mortality increases fast with too rich diets Mair Sept 2003, Science

11. it is never too late… improving the environment increases lifespan at old age Vaupel, 2003, Science

12. A general trend:mortality first grows exponentially and then slower

13. 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

14. Bacteriophages 12 10 Log (offspring/hour) 8 6 4 2 0 0 10 20 30 40 lifespan (days) Trade-off between life span and number of offsprings Mammals 180 10 0 5 0 Number of offspring (log scale) 2 0 15 1 0 0 0 10 20 30 40 50 60 70 80 lifespan (years) From R. Holliday, Understanding ageing, 1994

15. 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

16. Co-evolution lead tointeraction 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

17. 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

18. 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

20. Cigarettes & cancer Cairns, matters of life and death

23. Piccinini 2002

24. 8 0 7 0 6 0 5 0 4 0 S u b - S a h a r a 3 0 2 0 J a p a n Life Expectancy Trends: Paleolithic On U S A R u s s i a P a l e o l i t h i c n A f r i c a R o m e 1 0 0 , 0 0 0 ( 1 9 9 0 ) 1 0 0 0 0 ( 1 9 0 0 ) 1 0 0 0 P r e s e n t 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 )

25. Courbe de survie chez les chasseurs-cueilleurs

26. L’espérance de vie décroît à Rome… (les épidémies sont favorisées par la fréquence des contacts)

27. L’espérance de vie croît dès le 18e siècle…

28. Life expectancy still grows steadily & linearly Oepen, Science 2002

29. Gompertz law : mortality rate double every 8 years 1 10-1 10-2 death rate f rench woman 1994 10-3 10-4 0 20 40 60 80 100 age

30. Tuberculosis : environment before medicine ?! Cairns, matters of life and death

31. Tuberculose : effet modéré des antibiotiques ?!

32. Being rich helps but is not the only secret to long life

33. Mieux vaut être riche et en bonne santé !?

34. Effet de l’éducation sur la survie Cairns, matters of life and death

35. Interdisciplinary approaches of bacterial variability W h o c h a n g e s ? W h y c h a n g e ? M o l e c u l a r e p i d e m i o l o g y P o p u l a t i o n g e n e t i c s B i n g u e n D e n a m u r P i c a r d B r i s a b o i s B e r c h e G o d e l l e G o u y o n B r o w n M a y n a r d - S m i t h B . T o u p a n c e D u r i e z O . T e n a i l l o n J - B A n d r é H o w t o c h a n g e ? C h a n g e w h a t ? W h o h a s c h a n g e d ? M o l e c u l a r b i o l o g y B i o - i n f o r m a t i c s M o l e c u l a r P h y l o g e n y M a t i c R a d m a n V u l i c D i o n i s i o B j e d o v R o c h a B r e g e o n L e r o y H a y a k a w a S e k i g u c h i D u k a n L e c o i n t r e D a r l u G i r a u d L e c h a t B a m b o u C h a n g e w h e r e ? P h e n o t y p i c v a r i a b i l i t y & aging M i c r o b i a l e c o l o g y L i f e H i s t o r y C h a n g e w h e n ? F o n s S t e w a r t M a d d e n L i n d n e r t r a n s c r i p t o m e a n a l y s i s P a u l G a b r i e l F o n t a i n e D e p a e p e B r e d è c h e M o s s e r Diard K n u d s e n C e r f

36. Propagation des idées et des techniques (progrès technologiques, scientifiques, médicaux et communication) van Leeuwenhoek