Is Aging an Accident of Evolution? Stanford Scientists Say "Yes"

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July 29, 2008

Is Aging an Accident of Evolution? Stanford Scientists Say "Yes"

Main_2 "Everyone has assumed we age by rust. But how do you explain animals that don't age? Some tortoises lay eggs at the age of 100, there are whales that live to be 200 and clams that make it past 400 years."

Stuart Kim, PhD, Stanford University professor of developmental biology and genetics

Prevailing theory of aging challenged by Stanford University Medical School researchers. Their discovery contradicts the prevailing theory that aging is a buildup of tissue damage similar to rust. The Stanford findings suggest specific genetic instructions drive the process. If they are right, science might one day find ways of switching the signals off and halting or even reversing aging.

“We were really surprised,” said Stuart Kim, who is the senior author of the research.

Kim’s lab examined the regulation of aging in C. elegans, a millimeter-long nematode worm whose simple body and small number of genes make it a useful tool for biologists. The worms age rapidly: their maximum life span is about two weeks.

Comparing young worms to old worms, Kim’s team discovered age-related shifts in levels of three transcription factors, the molecular switches that turn genes on and off. These shifts trigger genetic pathways that transform young worms into social security candidates.

The question of what causes aging has spawned competing schools, with one side claiming that inborn genetic programs make organisms grow old. This theory has had trouble gaining traction because it implies that aging evolved, that natural selection pushed older organisms down a path of deterioration. However, natural selection works by favoring genes that help organisms produce lots of offspring. After reproduction ends, genes are beyond natural selection’s reach, so scientists argued that aging couldn’t be genetically programmed.

The alternate, competing theory holds that aging is an inevitable consequence of accumulated wear and tear: toxins, free-radical molecules, DNA-damaging radiation, disease and stress ravage the body to the point it can’t rebound. So far, this theory has dominated aging research.

But the Stanford team’s findings told a different story. “Our data just didn’t fit the current model of damage accumulation, and so we had to consider the alternative model of developmental drift,” Kim said.

The scientists used microarrays—silicon chips that detect changes in gene expression—to hunt for genes that were turned on differently in young and old worms. They found hundreds of age-regulated genes switched on and off by a single transcription factor called elt-3, which becomes more abundant with age. Two other transcription factors that regulate elt-3 also changed with age.

To see whether these signal molecules were part of a wear-and-tear aging mechanism, the researchers exposed worms to stresses thought to cause aging, such as heat (a known stressor for nematode worms), free-radical oxidation, radiation and disease. But none of the stressors affected the genes that make the worms get old.

So it looked as though worm aging wasn’t a storm of chemical damage. Instead, Kim said, key regulatory pathways optimized for youth have drifted off track in older animals. Natural selection can’t fix problems that arise late in the animals’ life spans, so the genetic pathways for aging become entrenched by mistake. Kim’s team refers to this slide as “developmental drift.”

“We found a normal developmental program that works in young animals, but becomes unbalanced as the worm gets older,” he said. “It accounts for the lion’s share of molecular differences between young and old worms.”

Kim can’t say for sure whether the same process of drift happens in humans, but said scientists can begin searching for this new aging mechanism now that it has been discovered in a model organism. And he said developmental drift makes a lot of sense as a reason why creatures get old.

“Everyone has assumed we age by rust,” Kim said. “But then how do you explain animals that don’t age?”

Some tortoises lay eggs at the age of 100, he points out. There are whales that live to be 200, and clams that make it past 400. Those species use the same building blocks for their DNA, proteins and fats as humans, mice and nematode worms. The chemistry of the wear-and-tear process, including damage from oxygen free-radicals, should be the same in all cells, which makes it hard to explain why species have dramatically different life spans.

“A free radical doesn’t care if it’s in a human cell or a worm cell,” Kim said.

If aging is not a cost of unavoidable chemistry but is instead driven by changes in regulatory genes, the aging process may not be inevitable. It is at least theoretically possible to slow down or stop developmental drift.

“The take-home message is that aging can be slowed and managed by manipulating signaling circuits within cells,” said Marc Tatar, PhD, a professor of biology and medicine at Brown University who was not involved in the research. “This is a new and potentially powerful circuit that has just been discovered for doing that.”

Kim added, “It’s a new way to think about how to slow the aging process.”

Posted by Casey Kazan.

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Bringing Ancient Human Viruses Back to Life: A Jurassic Park or Salvation?
Robot Evolution: A Parallel to the Origins of Life
Virtual Immortality -How To Live Forever
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A Post-Human Future: Are Humans the Limit of Evolutionary Complexity?



Adapted from the following source:
http://med.stanford.edu/news_releases/2008/july/aging-worm.html

Comments

Hmm, interesting. Some very valid points indeed.

JT
www.Ultimate-Anonymity.com

I dislike this whole notion that genes aren't affected after a species has gotten through its reproductive age. If an organism is still in the environment it still has an effect on the rest of the species. Therefore poor genes that cause detrimental effects to species propagation at old age will be weeded out.

Also, if things lived forever they would be susceptible to environmental changes that are out of reach of a species ability to adapt to in its life time. Death seems like a logical response to the interplay of a genes survival.

You make a very good point. Death is an essential part of evolution. It hardly seems possible that it's an accident.

the view is really nice ...........:)

Wow, some animals can live longer than us. What does that prove? Animals age, they just die before they get old like we used to.

It couldn't be an accident unless the accident happened at the beginning of life.

Genetically engineered lifespans by Evolution. There is a balance between frequency of offspring and life-span (life-span includes the reproductive portion and not just the total start-end). Because of predation and other risk factors, a turtle needs to live past 100 even though each season they lay hundreds of eggs - the survival of the turtle's genes through time requires them to still function past 100. Excessive reproduction and life-span would be bad for most species - imagine the damage a pair of rabbits could do if they had a working lifespan of 200 years.

Hmm. Need more time to cure cancer?

There are several misconceptions in this article.

I have a gene that makes me want to kill my grandchildren. But it's alright because "After reproduction ends, genes are beyond natural selection’s reach."

Why should "Rust", and "developmental drift" be considered exclusive alternatives? My refrigerator is slowly getting old, but I'm pretty sure the manufacturer is responsible for how it failed one week out of warranty.

Why should we consider aging to be a mistake? Cells undergo apoptosis (programmed cell death) for the benefit of the body. It's easy enough to see ways that "programmed individual death" could be good for the species. Or not.

“But then how do you explain animals that don’t age?” Given how few there are (and who says they don't age?) it seems more likely that those are the species with the genetic accident.

As a counter question, how does "developmental drift" explain the correlation between metabolism and lifespan?


I find this whole article to be really quite disappointing. I don't think there are "two camps" at all in this field. There is indeed a lot of speculation on exactly what adds up to ultimately cause ageing - but it is almost certain that there is no 'one thing'.

IN any case, this dichotomty presented here was long since dispelled by Williams (amongst others) in the 50s.

My favourite paper of all time is "Pleiotropy, Natural Selection, and the Evolution of Senescence" from 1957 by Williams. It explains why aging has evolved brilliantly. Best paper you'll ever read.

Wikipedia seems to have a good entry on the theory: http://en.wikipedia.org/wiki/Antagonistic_pleiotropy_hypothesis

Read it.

has anyone ever considered if the age of the parents has had anything to say about longevity? IE, would parents who are in their 40s have a better chance to bear children who live to be 100 while those who have kids in their 20s have a more likely chance to only make it to their 70s?

I had this thought, when considering what genetic material is being passed. If the genetic material being passed on is from someone in their 40s, there's more genetic experience, is there not? When life was shorter 2000 years ago, parents would often be almost preteens, and people lived to be 30 if they were lucky. (Of course there are a ton of other factors!)

Just wondering if there's much on this out there.

Aging may in fact be a favourable behaviour for a species. If you assume that an environmental niche for a species is fixed in size, then for a species that doesn't die of old age the older individuals would tend to occupy the niche and very few youngsters would survive to reproduce. This would have the effect of "freezing" the genetic makeup of the species as most replacement individuals would come from the same parents again and again. If evolution of genes is a survival mechanism, then this would be a Bad Thing. Therefore immortal species would tend to become extinct, while species that favour individual turnover would tend to evolve, expand, and take over.

Ahh to live forever. No thanks. Wouldn't mind not aging a day until I kick it, but immortality is out of the question.

Really though, I think aging plays a very critical role in the survival of our planet.

After all, what happens when no one dies after 100 years?

Should only take a shred of common sense to figure out what that would mean.

I believe, & I'm not alone in this, that back when the Earth was " new " ( Pre - Deluge & maybe Post ), that the human life - span was somewhat longer. Significantly shortened lifespans kicked in as the population began to increase, & perhaps as new diseases appeared. People began dying sooner to make room for new populations.

If mankind could attain " immortality " or near - immortalty via genetic engineering or some other means, extended lifespans could be both bane & blessing. Imagine a world full of Lazarus Longs suffering from terminal boredom & ennui. I'd like to live into a 2nd century, perhaps, but FURTHER than THAT ? I don't think I'd shoot for it. Pass.

mooey --

What is this within lifespan "genetic experience" you're talking about? Also, the lifespan thing has a lot more to do with infant and violent death than aging.

knoxvilledaniel --

We have longer and healthier life spans now than at any other time. Significantly lengthened life spans have kicked in with good nutrition and medicine.

When we talk of immortality, we assume people will sit around saying things like, "A thousand years ago, people were more polite". Actually, the documented limit of human memory, (without rehearsal), is about 50 years. We "immortals", would end up meeting our own children and saying things like "Who are you?", or worse, "Hey, you're cute, wanna come over and see my etchings?". Not for me.

Longevity is not a factor when selecting a mate; so it stands to reason that it's not a major factor when it comes to evolution. Most people are attracted to health and youth and they don't care whether someone's great grandparents are still around.

By the time someone hits 90 or 100, they're not reproducing anymore; therefore, a genetic tendency for longevity is not passed on to the next generation at a higher rate.

On the other hand, having children later in life sometimes leads to increased incidents of genetic problems. Perhaps we evolved the trait to age and die in order to minimize that risk.

Ben is close to the mark, IMO.

Both sex and death perform the same function: to widen the field of genetic options from which natural selection selects.

The reason why this is an advantage, is because the more variations there are at any given time in a species, the more likely it will be that one or more of them will prove to be useful when the environment changes. In other words, it expands the "oddball pool", which acts as a reservoir of variation from which those adpated to the new environments will spring.

Sex does it by forcing new combinations on a per-generation basis; without it, only mutation can create new combinations, very slowly -- unless the species lives on a natural uranium deposit.

Death does it by forcibly retiring existing combinations, to help prevent the currently successful combinations from being so dominant that the population becomes too homogenous -- and therefore, more vulnerable to extinction with environmental changes because the variation needed to survive in the new situation were lacking. (Think about tenure, and what it does to ossify university departments; this is the same idea).

It should be clear that immortality would be a short-run advantage for any one species; that mortality instead is the dominant trait, indicates that the genetic churn it facilitates is a much greater advantage in the long run.

Funny, you would think then - that insects and such would be at a greater evolutionary level than humans... as their life cycle's rotate quicker to stem cell genetic replacements by way that their mating rituals far outweigh humanities own.

So perhaps they are on a greater evolutionary track than us, maybe even in touch with the universe.. They do have antennae after all... They seam to follow the universal energies more closely than us. Maybe we are actually the slowest developers in the physical sense of evolution.

Maybe evolution leads us down the track of mechanical persistence to universal forces, perhaps it's the creation in our own minds eye that breaks the code to familiarises and processes us with a natural progression of choice - to hamper our growth and allow us a difference to succeed life to an imaginary proliferation of light acting from within the righteous practitioner of a god type concept of understanding. Factually placing our evolution to infinite status, as apposed to the en evadable death of the difference, that makes us the reflected image of god. Word be that. After all, progressively speaking, thinking only ever distracts us from having sex, eating food, and producing offspring. Creation evolution stops us from destroying our own choice of differentiated destiny.

Oooh dear, some painfully silly comments here. Quite a lot in fact.
Looks like evolution hasn't filtered out the mentally impaired and narrow minded quite aso much as one might hope for.
I guess that might have to do with the fact that natural selection hardly exists anyway in humans anymore and that you have completely forgotten to take that into account.
Most of you here are just full of preconceived crap and incapable of the slightest objectivity. Sadly, you are the average.

May the aging genes in you perform well and give the gene pool a second and hopefully better chance of heightening this bloody species.

With utter disgust,
R&D

it will suck is the aging is reversed because people will end up dating a 1hundred year old person, and with less people dieing from old age there will be overcrowding, which will lead to less food and land, and eventually people will kill each other because too many people and all the earth resources will be gone and earth will die

I like R&D's comment that "natural selection hardly exists anyway in humans anymore". I think what you meant to say is that it hardly exists in human society, since it can't really exist 'inside' anyone, natural selections refers to the interaction of environmental factors and gene pool groups. However I might point out that R&D is more correct than he/she realizes because natural selection doesn't 'exist' at all-it is merely a human concept based in culture and language not some independent entity. So how can it 'not' exist if it is the product of a social group and as far as I can see they seem to still exist and are entering posts on cyber space. Well perhaps in a 100 years people will 'evolve' beyound that kind of constructivist thinking
cheers

JIm Woods's response is very astute. When members of a species live together the group and not just the individual are subjected to natural selection. That means that indiviudals beyond reproductive age defintely influence evolution.

1) Longevity is not inherited. What determines longevity is first and foremost environment. Dont believe me? Look up Inherited Frailty and Longevity by J Vaupel, Demography Vol 25, 1988

2)Humans ARE still evolving and at a faster rate than in the past. Dont believe me? http://news.nationalgeographic.com/news/2007/12/071211-human-evolution.html

3)Overpopulation is not a concern if we continue to age. This is because as life expectancy increases fertility rates fall. This can be measured using death rates http://en.wikipedia.org/wiki/Demographic_transition

4)Extreme cases of aging are not isolated to the animal kingdom, some trees live for thousands of years.

How can they say that some species "don't age"?? Age is the progression of time, and time NEVER ceases, so this is a contradicting statement. Who would want to live for 400 years? If we "never aged" we'd technically still be children. Maturity is the development of an infant to a child to a teen to an adult to a senior to death. If there was "no aging" involved, we'd just deteriorate and deteriorate until we were dust. and if there were really NO aging whatsoever, we'd be infants our entire life and wouldn't be able to produce offspring much less fend for ourselves for our own survival. These people need to consider WHAT they are saying before they are saying it- they're just talking out their butts.

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