Human Aging: Is It an Accident of Evolution?

July 31, 2009

Human Aging: Is It an Accident of Evolution? - A Galaxy Insight

"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.

Comments

Why do people cling to the rust hypothesis when there are direct counterexamples? A whale lives 5200 times longer than a worm (or whatever). Come ON scientists! If a hypothesis doesn't fit your data throw it the hell out. Damn that makes me so mad! AAAHHHHG! (EXTREME RAGE)
Does anyone have a word out there for extreme anger when confronted with people who don't do the scientific method right? "beaker-rage"? Somebody help me here.

Posted by: tom | July 31, 2009 at 10:47 AM

And why do you Tom think you have understood everything about aging after reading this article? the 'rust hypothesis' is something that is confirmed by a plenty of data, DNA mutations accumulate, crosslinks between proteins keep them from working, the lysosomes accumulate a bigger amount of lipofuscine everyday, new molecules which are side effects of normal metabolism builds plaques that our normal enzymes can't destroy etc. etc.
All these things are a big problem for the normal function of our body when we age, and they're not stupid things we should throw the hell out. Aging is due to a complex set of causes, and C. Elegans will definately have a genetic important trigger, living 20 days. Anyway, Thomas E. Johnson, editor in chief of the important journal Experimental Gerontology, in the last world aging conference in Scottsdale showed his very interesting data on aging in a big set of syngenic Elegans individuals. They all had the same genome and lived the same conditions, anyway they showed very different paces of aging. We are studying it, nothing is worth being thrown the hell out.

Posted by: Lorenzo Albanello | July 31, 2009 at 03:54 PM

Gosh Lorenzo,
I hope you are better at identifying the causes of aging than you are at identifying humor. Otherwise we're all gonna die.

Nice job Lorenzo. Thanks a lot Lorenzo.

Posted by: tom | August 01, 2009 at 12:37 PM

We humans are rustying (oxidation in practical term)and then we are also subject to a number of other ageing factors spanning from bombardment (all frequency spectrum) from the sun and stars...to many other related to the environmnet we live into.

FAQ : does genetic DNA of humans hold an end of life rule ??

May be the answer is Yes.

Why ?? Becouse our genes may relate to old factors of survival of our ancestors correlated to other living species part of our (their) 'food chain'.

Is this theory proven ??

I would say : NO . Not at all.

We have to admit we know so little about 'genetics' and human DNA that all theories can be regarded as acceptable or at least NOT to be disregarded until different proof is obtained.

Regards to the humans that live not more than 80 Y (approx average)

Posted by: claudio | August 02, 2009 at 02:25 AM

human aging is directly related to first, Sin, when Adam and Eve disobeyed God's word. second, the results of that sin makes our body weak. there is no evolution (in the sense of evolution) as spoken by scientists and evolutionists. God cut short life after the universal flood of Noah.

we will have eternal life when Jesus comes again to take the righteous with Him. then we will have eternal life.

Posted by: roger | August 03, 2009 at 01:58 PM

ROGER IS A TROLL!

Posted by: tom | August 04, 2009 at 03:32 PM

Still on the subject in the trans human stage Francisco Varela existing uncomfortably with a grafted liver observered that somehow death should be given back its rights. Similarly Driven Pommel the Dutch cardiologist who has made detailed observations of near death experiences[now taken seriously in hospitals around Europe],witnessed patients who experienced feelings foreign to them with transplanted organs, somewhat compounded by Dennett’s altruistic proposal that we help others to help ourselves.Kohn adds a footnote that another challenged view of egoism is that we make ourselves feel better by not being in the others unfortunate situation leaving little room for empathy.
David Hume asked how can we be sure of minds [one wonders what he would have made of computer simulation or even animal simulation in his essay on human understanding in the light of Darwin’s Origin of the Species, the Greeks in a fantastic but puerile theory got there before Darwin anyway.
According to Heidegger we know of other minds[D ZAHAVI Beyond Empathy]we know of other minds by the utilities such as clothes produced for others as well as ourselves, The modern philosopher Alain de Botton approaches it in a more metaphysical manner. He asks us to imagine sitting waiting for a classical master piece to begin. We look around at the sea of unknown faces foreign to us separated by race, colour and creed, the music begins and we feel a more profound connection with our fellow enthusiast realizing that the work transcends us and others, known by their facial expressions s
 Similar to our own, our separation forgotten if only for this shared experience. Music and its empathic effect upon us is only one example sports, art and spiritual mysticism are others. How would computer simulation keep apace? Or indeed in moments of sheer ecstasy of epilecyic sufferers [Dostoeysksaid he could not exchange that brief interlude for anything else] Similar experiences have been reported in N DE S. The problem with Dr. Van lommen states that after clinical death we lose our particle aspect entirely -------we constantly shred billions of cells---------leaving only the wave part entering the Phase Space where all possible worlds exist-----including one of computer simulation. For each mind is a world/universe of its own. Imagining these universes is different to attempt to experience them that from the past attempts require fortitude and a good deal of resiliencies a deepening atmosphere of egoism and competition for the Alpha Male or Female status in TV Reality shows or anywhere else for that matter.
We d not know what lies beyond [the veil] but we do know that without consciousness we lack the dignity to think of what is possible. Quantum Mechanics has changed forever our perspective. As paradoxically said, the world is a queerer place than we imagined in fact a queerer place than we possibly imagine. But we cannot block out the mundane. As Tomas Hobbes said life is short, nasty and brutal. In modern parlance the good the bad and the ugly envers c est l autres according to Sartre and it is, when we think of the other as an object rather than a subject. One of the perpetrators of the present financial crisis Alan Green span tells us it will happen again because of human nature. Now is our chance to change our nature, if only for the sake of our dependants.
The only reality lies in thought which with consciousness in altered dimensions which as far as we are aware are infinite. Clearly computers will always be playing catch-up. Can they play the participating and inseparable role of observer and observed?
SEVERAL SECTIONS FAILED TO GET POSTED BUT IF ANYONE SHOULD BR REMOTELY INTERESTED I WILL TRY AGAIN ESPECIALLY FOR GLORIA.

Posted by: Brian M Williams | September 18, 2009 at 08:57 AM

5.Of course ,selfishness and egocentricity go back further as in late antiquity the epistle of St James testifies. This was thought to be written by the brother of the man spiritually now popularly reclog nosed as the awaited Jewish Messiah amongst others who had been in contention for this exulted position beforehand later including Simon Korbar at the fall of the Temple in AD 66 against the Romans which could be thought of the first FINAL SOLUTION of The Jewish Problem.
Much of the compassion, empathy and intersubectiveity attributed to the messianic figure had already been found in competing and former religious ideologies, but it was not until Freud and Jung practised their psychiatry into our preoccupation with our suppressed subconscious desires that overwhelmed the limitations of altruism as in the case of the Good Samaritan.
The magic of the Messiah as told by the Jewish historian Josephus possibly the only record of his existence was in the parables where he held up his own mirror to the egocentrism of others in the show stopping exhortation let him without sin cast the first stone. What St Paul wrote down in deterministic black and white he demonstrated in glorious Technicolor?
Also according to the Synoptic Gospels, which differ in context from the Gnosticism of Judas and Thomas possibly the twin of Jesus, the Pharisees rather unjustly, where made examples or clean outsides and unclean[self seeking insides]
It was St Paul who interpreted the empathy of Jesus as the basis to a new religion of compassing
To fit the Hebraic scripture of escape from bondage without realizing its metaphysical significance or the meaning of the classical Axel age dismissing it as ‘puffed-up wisdom. If per chance we are in a computer simulation the deterministic dogma of St Paul might not be contested except for his remark ------=In judging others we judge our selves.
Since the Freudian profundities of the mind only recently have in depth investigations into the multilayered sections of the mind started. In his book Robert Orstein states that we are by no means single-minded but an infinite collection of small minds. ………..more

John Maynard Keynes commented that we should clear all thoughts from every corner or the mind being equivalent to wearing our glasses for rethinking what we have learnt from the myriad of concepts collected by our mutiminds.Orstein also allows us clues to the origins of egoism. He contrasts the way the hackles rise during business meetings to show superiority with puffing up to ward off predators in the primordial soup.
An example of a multimind may be found in Richard Dawkins book The God Delusion--------The Sunday Times featured an article entitled Should Church and State be Separated. Dawkins was in favour commenting that every fair- minded person would agree. In his book he lambasted a theologian for failing to tell a friend of his own religious doubts [is their somebody without them?} by declaring that every sentence dripped with moral cowardice. He recently completed a series on television centered on Darwin without a mention of Darwin’s reluctance to publish for fear of upsetting people in the same manner as the previous religious doubts.
At the time of inept investigations into mind the trans-human stage had begun with the first human transplant. James Martin [The Meaning of the 21st Century] mentions how the privileged few [including Oxford Professors] will benefit from enhanced computer simulated intellectual powers whilst enjoying the luxury, for instance of original paintings hanging on the living room wall
A few centuries ago Hegel commented that what we learn from history is that we don’t learn from history, would then these privileged few be altruistic enough to relieve the misery of billions some of which are in 1st world countries who cannot afford basic health care? Not forgetting that Utopias such as those advocated by Plato, Thomas Moore and Hitler all featured eugenics. Traffic in human organs is already a big criminal operation.

Posted by: Brian M Williams | September 18, 2009 at 08:59 AM