The Evolution of AgingThe Evolution of AgingA GK-12 Project PresentationA GK-12 Project Presentation

Michael R. RoseMichael R. Rose

Dept. of Ecology and Evolutionary BiologyDept. of Ecology and Evolutionary Biology

University of California, IrvineUniversity of California, Irvine

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

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

Some Organisms Don’t AgeSome Organisms Don’t Age

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

It grows in the Mojave It grows in the Mojave Desert of CaliforniaDesert of California

It started life as a small It started life as a small bush, and grew bush, and grew outwards in a circle.outwards in a circle.

Some species age slowly,Some species age slowly, some very quickly some very quickly

The Longest Lived HumanThe Longest Lived Human

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

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

Of course we’re interested in agingOf course we’re interested in aging

Aging has Aging has been studied been studied from very from very different different perspectives, perspectives, including including evolutionary evolutionary biologybiology

Facts About Human AgingFacts About Human Aging

Life expectancy now Life expectancy now (US): pushing 80 years(US): pushing 80 years

Life expectancy without Life expectancy without aging: 1,200 years aging: 1,200 years based on the survival based on the survival rate at age 12rate at age 12

Here is what aging looks like Here is what aging looks like medicallymedically

Non-Non-contagious contagious diseases hit diseases hit older people older people with greater with greater and greater and greater force, killing force, killing us off, and us off, and making us making us debilitateddebilitated

Freedom from Major DiseasesFreedom from Major Diseases

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

At age 60 years, more At age 60 years, more than 50% of the than 50% of the population is free of population is free of major diseasemajor disease

By 85 years, only about By 85 years, only about 30%30%

There are plenty of quack “cures”There are plenty of quack “cures”

Ginseng, Ginseng, shown on the shown on the left, has been left, has been prescribed as prescribed as a “cure” for a “cure” for aging by aging by Chinese Chinese traditional traditional medicine for medicine for centuries.centuries.

Reproduction

Lethal gene not passed on

Lethal gene(s) passed on

Later Generations

Early Life Later Life (post-reproduction)

X

Timing of Reproduction Controls the Evolution of Aging

Here is a case of an early acting Here is a case of an early acting lethal gene lethal gene

The disease is known as The disease is known as Hutchinson-Gilford’s Hutchinson-Gilford’s progeriaprogeria

It starts to affect young It starts to affect young children (3-5 years of age)children (3-5 years of age)

Kills by 20 years of ageKills by 20 years of age Due to a single bad copy of Due to a single bad copy of

the gene at the Lamin A the gene at the Lamin A locuslocus

This is a very rare disease, This is a very rare disease, with just dozens of progeric with just dozens of progeric children alive at one timechildren alive at one time

Here is a case of a late acting lethal Here is a case of a late acting lethal gene gene

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

It starts to affect the brain of It starts to affect the brain of middle-aged adults over 30 middle-aged adults over 30 years of ageyears of age

Takes years to kill victims, Takes years to kill victims, breaking down coordination, breaking down coordination, IQ, personality, as it goesIQ, personality, as it goes

Due to a single bad copy of Due to a single bad copy of gene at the Huntington locusgene at the Huntington locus

This is a common genetic This is a common genetic disease, with many thousands disease, with many thousands of victims alive at one timeof victims alive at one time

Reproduction

Lethal gene not passed on

Lethal gene(s) passed on

Later Generations

Early Life Later Life (post-reproduction)

X

Timing of Reproduction Controls the Evolution of Aging

Why some organisms don’t ageWhy some organisms don’t age

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

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

Reproduction

DeleteriousMutations

= Longer, more robust lifespan

Postponing Reproduction forces early acting deleterious genes out

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

Here’s Where Young Flies LiveHere’s Where Young Flies Live

We rear our flies in We rear our flies in vials with controlled vials with controlled densitiesdensities

The food goes in the The food goes in the bottom of the vial and bottom of the vial and the top is plugged so the top is plugged so they can’t fly outthey can’t fly out

Our Fruit Fly Old Age HomeOur Fruit Fly Old Age Home

How we control reproductionHow we control reproduction

Later egg collectionLater egg collection

larval rearing

Day 14

Day 14

Day 70

Egg collectionEgg collection

Egg collectionEgg collection

Reproduction

DeleteriousMutations

= Longer, more robust lifespan

Postponing Reproduction forces early acting deleterious genes out

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

Meaning of the Experimental ResultMeaning of the Experimental Result

This result showed that the idea of aging being This result showed that the idea of aging being timed by the force of natural selection is the timed by the force of natural selection is the best available theory as to the cause of agingbest available theory as to the cause of aging

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

But can we stop our own aging?But can we stop our own aging?

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

What if we were to delay human What if we were to delay human reproduction?reproduction?

It would take many generations – now more It would take many generations – now more than 700 fruit fly generations have gone by in than 700 fruit fly generations have gone by in my delayed-breeding experiments my delayed-breeding experiments

In human terms, that would be around 700 x In human terms, that would be around 700 x 25 years: 17,500 years25 years: 17,500 years

So even if we set about confining female So even if we set about confining female reproduction to women over 40 and male reproduction to women over 40 and male reproduction to over 60, we would have to reproduction to over 60, we would have to wait tens of thousands of years for such a big wait tens of thousands of years for such a big improvement in human aging by evolutionimprovement in human aging by evolution

Proposed Methuselah Mouse: Proposed Methuselah Mouse: Delayed breeding to let evolution tell Delayed breeding to let evolution tell

us how to slow mammalian agingus how to slow mammalian aging Let Let Evolution by Evolution by

Natural Selection Natural Selection supply us with the supply us with the answer to the question answer to the question of how to build a of how to build a longer-lived mammallonger-lived mammal

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

ConclusionsConclusions

We know now We know now whywhy aging happens: the aging happens: the declining force of natural selection with agedeclining force of natural selection with age

And we know that we can experimentally And we know that we can experimentally manipulate both the rate and the end of agingmanipulate both the rate and the end of aging

There are ways in which could postpone There are ways in which could postpone human aging, and I have described one of human aging, and I have described one of these approachesthese approaches

This is not a “should” argument, just a “could”This is not a “should” argument, just a “could”