1. The Evolution of Aging A GK-12 Project Presentation Michael R. Rose Dept. of Ecology and Evolutionary Biology University of California, Irvine

2. The survival and fertility of plants and animals usually changes with age, typically getting worse

3. So why do animals and plants often fall apart with age?

4. Some Organisms Don’t Age This creosote bush has lived for more than 10,000 years. This creosote bush has lived for more than 10,000 years. It grows in the Mojave Desert of California It grows in the Mojave Desert of California It started life as a small bush, and grew outwards in a circle. It started life as a small bush, and grew outwards in a circle.

5. Some species age slowly, some very quickly

6. The Longest Lived Human Madame Jeanne Calment lived 122 years, dying in 1997. Madame Jeanne Calment lived 122 years, dying in 1997. She sold paintbrushes to Vincent Van Gogh in her home town of Arles, France. She sold paintbrushes to Vincent Van Gogh in her home town of Arles, France.

7. Of course we’re interested in aging Aging has been studied from very different perspectives, including evolutionary biology Aging has been studied from very different perspectives, including evolutionary biology

8. Facts About Human Aging Life expectancy now (US): pushing 80 years Life expectancy now (US): pushing 80 years Life expectancy without aging: 1,200 years based on the survival rate at age 12 Life expectancy without aging: 1,200 years based on the survival rate at age 12

9. Here is what aging looks like medically Non- contagious diseases hit older people with greater and greater force, killing us off, and making us debilitated Non- contagious diseases hit older people with greater and greater force, killing us off, and making us debilitated

10. Freedom from Major Diseases Freedom from cardiovascular disease, cancer, kidney disease, etc. Freedom from cardiovascular disease, cancer, kidney disease, etc. At age 60 years, more than 50% of the population is free of major disease At age 60 years, more than 50% of the population is free of major disease By 85 years, only about 30% By 85 years, only about 30%

11. There are plenty of quack “cures” Ginseng, shown on the left, has been prescribed as a “cure” for aging by Chinese traditional medicine for centuries. Ginseng, shown on the left, has been prescribed as a “cure” for aging by Chinese traditional medicine for centuries.

12. Reproduction Lethal gene not passed on Lethal gene(s) passed on Later Generations Early LifeLater Life (post-reproduction) X Timing of Reproduction Controls the Evolution of Aging

13. Here is a case of an early acting lethal gene The disease is known as Hutchinson-Gilford’s progeria The disease is known as Hutchinson-Gilford’s progeria It starts to affect young children (3-5 years of age) It starts to affect young children (3-5 years of age) Kills by 20 years of age Kills by 20 years of age Due to a single bad copy of the gene at the Lamin A locus Due to a single bad copy of the gene at the Lamin A locus This is a very rare disease, with just dozens of progeric children alive at one time This is a very rare disease, with just dozens of progeric children alive at one time

14. Here is a case of a late acting lethal gene The disease is known as Huntington’s Disease The disease is known as Huntington’s Disease It starts to affect the brain of middle-aged adults over 30 years of age It starts to affect the brain of middle-aged adults over 30 years of age Takes years to kill victims, breaking down coordination, IQ, personality, as it goes Takes years to kill victims, breaking down coordination, IQ, personality, as it goes Due to a single bad copy of gene at the Huntington locus Due to a single bad copy of gene at the Huntington locus This is a common genetic disease, with many thousands of victims alive at one time This is a common genetic disease, with many thousands of victims alive at one time

15. Reproduction Lethal gene not passed on Lethal gene(s) passed on Later Generations Early LifeLater Life (post-reproduction) X Timing of Reproduction Controls the Evolution of Aging

16. Why some organisms don’t age Aging should not evolve in fissile organisms because natural selection stays strong; it has to Aging should not evolve in fissile organisms because natural selection stays strong; it has to

17. Evolution of Aging is predicted for all strictly non-fissile organisms

18. Reproduction Deleterious Mutations = Longer, more robust lifespan Postponing Reproduction forces early acting deleterious genes out

19. Changing the force of natural selection can produce rapid evolution of aging patterns

20. Here’s Where Young Flies Live We rear our flies in vials with controlled densities We rear our flies in vials with controlled densities The food goes in the bottom of the vial and the top is plugged so they can’t fly out The food goes in the bottom of the vial and the top is plugged so they can’t fly out

21. Our Fruit Fly Old Age Home

22. How we control reproduction Later egg collection larval rearing Day 14 Day 70 Egg collection

23. Reproduction Deleterious Mutations = Longer, more robust lifespan Postponing Reproduction forces early acting deleterious genes out

24. Changing the force of natural selection can force the evolution of aging patterns: data after 80 long generations

25. Meaning of the Experimental Result This result showed that the idea of aging being timed by the force of natural selection is the best available theory as to the cause of aging This result showed that the idea of aging being timed by the force of natural selection is the best available theory as to the cause of aging Also showed that adult life is characterized at first by a weakening force of natural selection Also showed that adult life is characterized at first by a weakening force of natural selection

26. But can we stop our own aging? Does evolution offer us any hope for changing our own pattern of aging? Does evolution offer us any hope for changing our own pattern of aging?

27. What if we were to delay human reproduction? It would take many generations – now more than 700 fruit fly generations have gone by in my delayed-breeding experiments It would take many generations – now more than 700 fruit fly generations have gone by in my delayed-breeding experiments In human terms, that would be around 700 x 25 years: 17,500 years In human terms, that would be around 700 x 25 years: 17,500 years So even if we set about confining female reproduction to women over 40 and male reproduction to over 60, we would have to wait tens of thousands of years for such a big improvement in human aging by evolution So even if we set about confining female reproduction to women over 40 and male reproduction to over 60, we would have to wait tens of thousands of years for such a big improvement in human aging by evolution

28. Proposed Methuselah Mouse: Delayed breeding to let evolution tell us how to slow mammalian aging Let Evolution by Natural Selection supply us with the answer to the question of how to build a longer-lived mammal Let Evolution by Natural Selection supply us with the answer to the question of how to build a longer-lived mammal And then reverse- engineer its answer to develop anti-aging therapies for genetically unaltered humans And then reverse- engineer its answer to develop anti-aging therapies for genetically unaltered humans

29. Conclusions We know now why aging happens: the declining force of natural selection with age We know now why aging happens: the declining force of natural selection with age And we know that we can experimentally manipulate both the rate and the end of aging And we know that we can experimentally manipulate both the rate and the end of aging There are ways in which could postpone human aging, and I have described one of these approaches There are ways in which could postpone human aging, and I have described one of these approaches This is not a “should” argument, just a “could” This is not a “should” argument, just a “could”