The Evolution of Aging

A GK-12 Project Presentation

Michael R. Rose Dept. of Ecology and Evolutionary Biology University of California, Irvine

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

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

Some Organisms Don’t Age

 This creosote bush has lived for more than 10,000 years.

 It grows in the Mojave Desert of California  It started life as a small bush, and grew outwards in a circle.

Some species age slowly, some very quickly

The Longest Lived Human

 Madame Jeanne Calment lived 122 years, dying in 1997.

 She sold paintbrushes to Vincent Van Gogh in her home town of Arles, France.

Of course we’re interested in aging

 Aging has been studied from very different perspectives, including evolutionary biology

Facts About Human Aging

 Life expectancy now (US): pushing 80 years  Life expectancy without aging: 1,200 years based on the survival rate at age 12

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

Freedom from Major Diseases

 Freedom from cardiovascular disease, cancer, kidney disease, etc.

 At age 60 years, more than 50% of the population is free of major disease  By 85 years, only about 30%

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.

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

Here is a case of an early acting lethal gene

     The disease is known as Hutchinson-Gilford’s progeria It starts to affect young children (3-5 years of age) Kills by 20 years of age 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

Here is a case of a late acting lethal gene

     The disease is known as Huntington’s Disease 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 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

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

Why some organisms don’t age

 Aging should not evolve in fissile organisms because natural selection stays strong; it has to

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

Postponing Reproduction forces early acting deleterious genes out Reproduction Deleterious Mutations

= Longer, more robust lifespan

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

Here’s Where Young Flies Live

 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

Our Fruit Fly Old Age Home

How we control reproduction

larval rearing Day 14 Egg collection Day 14

Later egg collection

Day 70 Egg collection

Postponing Reproduction forces early acting deleterious genes out Reproduction Deleterious Mutations

= Longer, more robust lifespan

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

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  Also showed that adult life is characterized at first by a weakening force of natural selection

But can we stop our own aging?

 Does evolution offer us any hope for changing our own pattern of aging?

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  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

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 And then reverse engineer its answer to develop anti-aging therapies for genetically unaltered humans

Conclusions

 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   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”