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. 1E-4 1E-3,01,1 1 death rate f rench woman 94 020406080100 age 10 100 1000 medical cost france 0102030405060708090100 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

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

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

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. Trade-off between life span and number of offsprings 180 lifespan (years) Number of offspring (log scale) 01020304060705080 100 50 20 15 10 0 From R. Holliday, Understanding ageing, 1994 Mammals 0 2 4 6 8 10 12 010203040 lifespan (days) Bacteriophages Log (offspring/hour)

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 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

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. n Africa Russia Japan USA Rome Paleolithic Life Expectancy Trends: Paleolithic On Present (1990) (1900)1000 10000 100,000 Years before present (log scale)

25. Courbe de survie chez les chasseurs-cueilleurs

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

27. Lespérance de vie croît dès le 18e siècle…

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

29. 10 -4 10 -3 10 -2 10 -1 1 death rate f rench woman 1994 020406080100 age Gompertz law : mortality rate double every 8 years

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 léducation sur la survie Cairns, matters of life and death

35. Why change ? Population genetics Godelle Gouyon Brown Maynard-Smith Change where ? Microbial ecology Fons Who changes ? Molecular epidemiology Binguen Denamur Picard Brisabois Berche Interdisciplinary approaches of bacterial variability Giraud Lechat Bambou B. Toupance O. Tenaillon J-B André Duriez Change what? Bio-informatics Rocha Who has changed ? Molecular Phylogeny Lecointre Darlu How to change ? Molecular biology Matic Radman Vulic Dionisio Bjedov Bregeon Leroy Hayakawa Sekiguchi Dukan Change when ? transcriptome analysis Knudsen Cerf Phenotypic variability & aging Life History Stewart Madden Lindner Paul Gabriel Fontaine Depaepe Bredèche Mosser Diard

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