It afflicts every creature on this planet, and everyone dreams of an antidote. But even after decades of research, aging largely remains a mystery. Now new research findings suggest there is a good reason for this impasse: scientists may have been thinking about the causes of aging all wrong. Instead of being the result of an accumulation of genetic and cellular damage, new evidence suggests that aging may occur when genetic programs for development go awry.
The idea that stress and reactive forms of oxygen—“free radicals” that are the normal by-products of metabolism—cause aging has dominated the field for 50 years. Studies on the worm Caenorhabditis elegans have shown that reducing exposure to reactive oxygen species increases life span, and worms that have been bred to live longer are also more resistant to stress. But few studies have definitively linked oxidative damage to altered cellular function.
Scientists have also noticed that intrinsic genetic changes accompany aging. As mice age, a gene called p16INK4a, which controls cell growth and regeneration, becomes more active in most tissues, preventing the cells from regenerating as easily as younger cells do in response to injury or disease. And compared with muscle stem cells in young mice, those in older mice accumulate a complex of proteins that, over time, transform muscle into fibrous, fatty tissue.
These findings did little, however, to challenge the idea that aging is the result of damage accumulation, because these genetic changes may simply be a consequence of aging rather than the culprit. “That’s always the challenge, to try to get cause and effect,” says Brian Kennedy, a biochemist at the University of Washington. And although studies have shown that changing the expression of certain genes can affect an organism’s life span, it is unclear whether these genes are actually involved in the normal aging process.
A recent paper published in the journal Cell, however, suggests that genetic programs do drive aging. Scientists at Stanford University and the University of Colorado at Boulder compared the genes that turn on in young nematode worms with those expressed in old worms. Although more than 1,000 genes differed, most of them were under the control of just three, called ELT-3, ELT-5 and ELT-6. These genes are transcription factors—molecular switches that turn other genes on and off. “There were hundreds of things that had gone awry, but they were all traced back to these three transcription factors,” which are known to be involved in the development of specialized membranous cells, explains Stanford developmental biologist and study co-author Stuart Kim. The expression of the three transcription factors also differed in young and old worms.
To see whether damage accumulation ultimately affected these transcription factors, the scientists exposed worms to oxidative stress, infection and radiation, but nothing affected the factors’ expression. The changes “seem to be intrinsic to the genome of the worm,” Kim says—not brought on by outside influences. In addition, when the researchers stopped the expression of ELT-5 and ELT-6, which typically become more active in old age, the worms lived 50 percent longer. “I was totally surprised,” Kim remarks.
The study’s findings also agree with conventional wisdom linking life span to reduced calorie intake. The researchers found that the three transcription factors are under the control of the insulinlike signaling pathway, which controls how an organism’s metabolism changes in response to famine. One of the things the insulinlike signaling pathway does during periods of caloric restriction, Kim says, is to reset the ELT transcription factors and their counterparts in other organisms “to a younger state.” Scientists believe that the plant compound resveratrol, which increases life span in some organisms, mimics the effects of caloric restriction and resets these pathways, too.
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Add CommentWhen Protons are almost at Light speed why don't they get so heavy that they become impossible to move, or shrink to nothing? (Einstien)
Reply | Report Abuse | Link to thisi love this description!!!!!!!!
Reply | Report Abuse | Link to this"When Protons are almost at Light speed why don't they get so heavy that they become impossible to move, or shrink to nothing? (Einstien)"
Reply | Report Abuse | Link to thisWhat does that have to do with cellular aging?
Protons aside, this article indicates to me that the evolutionary analysis of aging and death has not proceeded to a logical conclusion, perhaps due to lingering sentimentality about nature. The fate of the male praying mantis should be a lesson to us: the selfish gene has a clear interest in proactively removing competitors for resources. Adults that have procreated (and in more loosely programmed species, have finished childrearing) are competitors with their offspring. Mutations that remove them from the playing field would be selected for. Here's your "death wish".
Reply | Report Abuse | Link to thisIf we didn't age, how would the young complete with us? With all my experience and accumulated wealth, why would a young woman choose a young man? His youth and vigor is his only advantage. Come to think of it, why would I choose a young woman if an older one was still vigorous and fertile? An older woman would also contribute more wealth and experience to our young. Where would that leave evolution? If you don't die and make room for the new 'version', evolution stops. So species whose genes don't direct them to age died out long ago. Species which age slowly, evolve slowly. Somewhere in our genome there is a switch (or two...).
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Reply | Report Abuse | Link to thisThe New Younger Model? I'm a happy weathly older model female version doesn't need body part replacement yet, however it would be nice to turn on a gene to clean up the growing slop under my eyes, take a few thousand protons off the trunk, renew, recycle and reuse the upper half which is melting due to "global warming".
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I am not a person with formal university education on this subject you have written. I found it very informative. In my own way, I have attained subtantial global knowledge in almost every subject. Granted what in your article are true, and we proved there are switches in our selves that turns on or off our aging process, how will that alter our evolution? It appears to me if humans could live to over 150 years or cloned over and over, it will slow down our evolution. It will probably slowdown population explosion, but at what cost? Disease causing organism could evolved to more potent and virulent versions on each long aging population that it may extinct our future generations. Have we consider that atleast? I don't believe in the thought of Pandora Box. But I believe in the duality of everything that exist.
Reply | Report Abuse | Link to thisAnd for that we should approached what we want to do with caution and considerations. If you already did, I thank you.
Well, I agree that there must be a intrinsic switch or switches in different stages of human developmental process because no matter how different of the life spans between different people, all human beings go through from a baby to a old person. This paper about ELTs explained that deletion of ELTs extended mouse life span, but didn't elucidate whether deletion of the three ELTS with different combination or sequences and even doses can affect the stages of the development of mice. Still, cellular and molecular damages caused by mental and physical stresses acculated in a life time can reach a poisonous level to affect the normal funtion of body system and further affect a person's health and cause aging of organs and loss of life. So restricted calory intake , adequate amount of exercises, healthy foods, and regular life style together will help to extend the life span.
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