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

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

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

1E-4 1E-3,01,1 1 death rate f rench woman age medical cost france 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 between modelling & 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) Number of offspring (log scale) From R. Holliday, Understanding ageing, 1994 Mammals lifespan (days) Bacteriophages Log (offspring/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 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

Cigarettes & cancer Cairns, matters of life and death

Piccinini 2002

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

Courbe de survie chez les chasseurs-cueilleurs

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

Lespérance de vie croît dès le 18e siècle…

Life expectancy still grows steadily & linearly Oepen, Science 2002

death rate f rench woman 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 léducation sur la survie Cairns, matters of life and death

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

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