Scientists identify new longevity genes

Mar 12, 2008

Scientists at the University of Washington and other institutions have identified 25 genes regulating lifespan in two organisms separated by about 1.5 billion years in evolutionary change. At least 15 of those genes have very similar versions in humans, suggesting that scientists may be able to target those genes to help slow down the aging process and treat age-related conditions. The study will be published online by the journal Genome Research on March 13.

The two organisms used in this study, the single-celled budding yeast and the roundworm C. elegans, are commonly used models for aging research. Finding genes that are conserved between the two organisms is significant, researchers say, because the two species are so far apart on the evolutionary scale -- even farther apart than the tiny worms and humans. That, combined with the presence of similar human genes, is an indication that these genes could regulate human longevity as well.

"Now that we know what many of these genes actually are, we have potential targets to go after in humans," said Brian Kennedy, UW associate professor of biochemistry and one of the senior authors of the study. "We hope that in the future we could affect those targets and improve not just lifespan, but also the 'health span' or the period of a person's life when they can be healthy and not suffer from age-related illnesses."

Several of the genes that the scientists identified as being involved in aging are also connected to a key nutrient response pathway known as known as the Target of Rapamycin, or TOR. That finding gives more evidence to the theory that calorie intake and nutrient response affect lifespan by altering TOR activity. Previous studies have found that drastically restricting the caloric intake of organisms, an approach known as dietary restriction, can prolong their lifespan and reduce the incidence of age-related diseases. TOR inhibitors are being tested clinically in people for anti-cancer properties, and this work suggests they may also be useful against a variety of age-associated diseases.

"What we'd like to eventually do is be able to mimic the effects of dietary restriction with a drug," explained Matt Kaeberlein, another senior author on the paper and a UW assistant professor of pathology. "Most people don't want to cut their diet that drastically, just so they may live a little longer. But someday in the future, we may be able to accomplish the same thing with a pill."

These findings also give new insight into the genetic basis of aging, the scientists said, and provide some of the first quantitative evidence that genes regulating aging have been conserved during the process of evolution. Earlier evolutionary theories suggested that aging was not genetically controlled, since an organism does not get any advantage in natural selection by having a very long lifespan that goes far past their reproductive age.

To find these lifespan-controlling genes, the scientists took a genomic approach to comprehensively examine genes that affect aging in yeast and worms. Based on published reports, they first identified 276 genes in C. elegans that affected aging, and then searched for similar genetic sequences in the yeast genome. Of the 25 aging-related genes they found in both worms and yeast, only three had been previously thought to be conserved across many organisms.

Source: University of Washington

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User comments : 22

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zevkirsh
1 / 5 (1) Mar 12, 2008
the dream lives on. god bless.
AdseculaScientiae
not rated yet Mar 12, 2008
dream coming true later this century..?
googleplex
not rated yet Mar 12, 2008
I think the 'messy' biological issues will be eclipsed by a complete brain scan and backup (ca. 2050, source: Ray Kurzweil). Then when a brain simulation is available the backup is restored as a computer simulation (a la Vanilla Sky).
For those are not planning on living until 2050, the only current option is cryo storage which has debatable efficacy. In addition the candidate needs to pass on at a pre-planned time and place to get a "fresh" brain freeze.
AdseculaScientiae
not rated yet Mar 12, 2008
googleplex, sounds great (I really like people like Nick Bostrom, Ray Kurzweil, Aubrey de Grey etc.), but won't these backups and simulations, be LIKE you, but not fully you? I'd really like to have my personal brain contained.
MGraser
5 / 5 (1) Mar 13, 2008
Adsecula, what makes you who you are? If you were to move your brain to another highly similar body (so as to minimize the trauma of body parts not being the same proportion or acting the same as your brain memorized them), is it still you? I think most people would say "yes", because they feel the brain somehow contains them. The rest of the body is controlled by you, via the brain. Therefore, you as the entity is primarily the brain (this is my unfounded supposition, but it seems reasonable).

Now, consider that you take an exact copy of your brain and replicate it in new "brain material". Replace your old brain with the new one in your original body. Is it still you? You would think exactly the same as you did before, because you still have all the same memories and know how to do all the same things. You wouldn't perceive any differences. There would simply be a lack of time for which you couldn't account during brain transfer. So, I bet YOU would still think you were the same person, even if others were debating the fact.

Finally, make that replica, but place it in a similarly styled new body. Again, after adjusting to the trauma of the new body, YOU would still think you were yourself.

So, the question is - If they could back up your brain and replicate it either physically or electronically, why wouldn't it be you? Just because your brain is made out of different matter? Would you argue that one molecule of H2O is different from another? If not, then if your brain were molecule for molecule arranged in the exact same pattern as the old brain. How is it different? Just a thought.
DKA
not rated yet Mar 13, 2008
Take a brain dead living body, remove the brain and put yours inside. Today, research has progressed and can't it offer bypass to the spinal cord when it is ruptured? And re-connect to brain to it? Maybe today's closest path very long life? Species with death programmed in their genes outdid very early species that might have had eternal life and could not adapt to any change. but that does not mean it is not possible to turn off those genes. It might even be easier to do than for other genese.
superhuman
not rated yet Mar 13, 2008
If science does develops ways to significantly delay aging and death it will lead to a major global conflict.
DGBEACH
not rated yet Mar 13, 2008
The phrase "Spending my kid's inheritance" would take on a whole new meaning :)
I can't imagine working well into my 100s and beyond. I'll take the retirement package, thank you very much.
AdseculaScientiae
not rated yet Mar 13, 2008
DGBEACH, with the coming Artificial Intelligence revolution, I don´t think we humans need to work anymore? Presuming that our wealth/technology/science will be so much more at the end of this century, we should be careful not to have a static view on that our future looks exactly or somewhat like now.
AdseculaScientiae
not rated yet Mar 13, 2008
MGrazer, thank you for your reply to me. I do think that our brain is the (only and?) most important part of our being, but this is really speculative philosophy I guess.. If someone could make a copy of my brain and put it in a hypothetical body, I think I would call it more of a clone of me than a full version of me. Especially when I could be alive while this copy of me is living besides me. That's not me, right? It's an other conscious being líke me.

It's very the issue of what being conscious exactly means and 'what its concensus is'. If someone uploaded my mind onto a computer, I don't know if I, individually, am still in control over my consciousness? Now you wouldn't know, because you then, could be non-existent already and the uploaded being would feel 100% like me.

Religious people would bring the argument of the Soul here, but I don't believe that.

It's still a hard thing to really think of what would happen, and I guess it could never be tested.

But what do we have to lose.. right?;)
Modernmystic
1 / 5 (2) Mar 13, 2008
I think the big problem with some of these immortality schemes is that there is a break in continuity of your consciousness. Downloading yourself into another brain, or into a computer is not immortality unless it's done in a manner that ACTUALLY transfers your consciousness rather than simply copying it. If you are copied, it's not you, it's memorex.
googleplex
not rated yet Mar 13, 2008
googleplex, sounds great (I really like people like Nick Bostrom, Ray Kurzweil, Aubrey de Grey etc.), but won't these backups and simulations, be LIKE you, but not fully you? I'd really like to have my personal brain contained.


Response:
Yes it would be you. The caveat is that chaos theory comes into play. Identical twins are not identical. Drop a grain of salt onto the same pile of salt and it falls a different way.

They will/are testing the 'in silica' model against 'in vivo'. Back up a live brain, restore in virtual simulation, run for 1 day, analyse the variance.

Are you aware that IBM are already well on the way. http://en.wikiped...ue_brain
Resolution of brain scans is improving along the lines of Moores law too.

Don't worry about work. Before brain backups we will have mastered AI. This renders the price of human thought to pennies per day. The robotics is already here (Asimo etc). It is just the AI piece that is missing. So price of labor drops by 2 or 3 orders of magnitude. The disruption to society is hard to predict. History would inicate that life will get easier and leisure time will increase. On the darkside there is a real risk of a "Terminator" scenario.
superhuman
not rated yet Mar 13, 2008
Brain scans would never suffice, neurons have genetic memory which would have to be read out and copied too, and that is WAY beyond our current capabilities.

As for Blue Brain, we cant simulate even a single bacterial cell, which is 1000x smaller and way simpler than a neuron and they want to simulate entire brain at molecular level.
A realistic single(!) protein folding requires a whole grid of computers, and we have many thousands of those proteins in a single neuron.
Not to mention that there is an impressive amount of knowledge about neurons still missing.

Thats not to say that Blue Brain wont simulate something, they will develop some extremely simplified (when compared to nature) model and maybe even discover something interesting with it, but its completely different story to your "brain backup".

Many people in the 1960 believed that by 2000 we will colonize the stars...
AdseculaScientiae
not rated yet Mar 13, 2008
@superhuman
Yes, and they said the Human Genome Project would take several centuries to complete at the beginning right..?
@googleplex
Yes, I am aware of it. Read a great article about it a week ago, link: http://www.seedma...page=all&p=y
Argiod
2 / 5 (4) Mar 14, 2008
So much research into extending the span of people's lives; with no effort put into researching quality of life issues. Just what are we going to do about controlling the number of humans the Earth has to support, once we are able to live longer? How are we going to feed all these people? Already, we thwart nature's controls by decreasing infant mortality and have pushed old age back by several decades. Long life is a great idea; but not at the expense of having to be up to our eyeballs in people, with insufficient resources to support them all. Earth is, after all, a set of very finite resources. Just how many people can it support in any degree of comfort and dignity?
AdseculaScientiae
not rated yet Mar 14, 2008
@Argiod
I don't think we are the only ones to see these problems. But it's not right to say that we are not improving the quality of our lives besides this. Many scientists are really thinking hard on these issues and how to improve and eliminate these problems preventively when they should arise. I'm not in favor of longer life with less quality, but I do think BOTH will improve these next decennia.
zevkirsh
not rated yet Mar 14, 2008
the benefits of longevity will be reaped by the richest rich people, who'se healthspan, and lifespan will allow them to increase their fortunes and conquer the world financial system. Imagine warren buffet living in good health for another 30 years till his early 100's. His continued existence would change things greatly from what would otherwise happen if he died. you can't say that about any other joe.

AdseculaScientiae
not rated yet Mar 14, 2008
@zevkirsh
What about free market and the growing demand of consumers?
ouroboros
5 / 5 (1) Mar 15, 2008
I find this stuff fascinating. If pharmaceutical companies can develop drugs that target these genes, we may have real anti-aging medicines sooner than you might guess. The great thing about such a drug is that if it really slows aging it should be effective at preventing all of the major age-associated diseases %u2013 Alzheimer%u2019s, cancer, diabetes, cardiovascular disease.
RNSeitz
5 / 5 (3) Mar 15, 2008
I'm surprised at how many people are apparently unaware that they may already be able to increase their "youth spans" by, perhaps, 10-to-20 years. For example, eating an ounce of nuts (e. g., almonds) seems to extend life spans by one-to-two years. California Seventh-day Adventists who are vegetarians seem to enjoy life span extensions averaging something like six years. (Of course, California Seventh-Day Adventists don't smoke and probably practice general good health habits compared with the general population.) One recent study (http://www.washin...pf.html) of the effect of exercise (over a 10-year time frame) on telomere lengths in 2,401 British twins found that those who had gotten 180 minutes a week of moderate-to-vigorous exercise over at least a 10-year period had telomeres that were about 9 years younger than those of sedentary subjects who averaged 16 minutes of moderate-to-vigorous exercise a week. "When the researchers compared the least and most active twins with each other, they found about four years' difference in their telomeres, Spector said. 'We wanted to see if we could account for the effect of genes,' he said."

Another gambit is that of calorie restriction: bringing our weights down to the slim-and-trim weights most of us had in our early twenties, and keeping them there (Body Mass Index in the 18-22 range). No, it doesn't mean going cold and hungry, or never eating pizza or chocolate ice cream again... it just means staying on a permanent diet... something many of us have to do anyway, to keep from bulking up like Colonel Blimp. (But note that weight loss shouldn't occur faster than, perhaps, a pound a week, and that carefully chosen diets are required to insure that you get proper nutrition--something that should be observed anytime someone goes on a diet. Further information about calorie restriction and about safe calorie restricted diets can be found on The Calorie Restriction Society website at (http://www.calori...n.org/). In 2004, researchers at the Washington University School of Medicine made the watershed discovery that calorie restriction in humans begun in mid-life produces dramatic improvements in blood lipid profiles (http://www.pnas.o...1101v1), and in other physiological parameters characteristic of those who are 10-to-15 years younger than the (typical couch-potato: BMI = 25) subjects of the study (15 men and 3 women) who had begun a calorie restriction reginen a few years earlier. An ultrasonic examination of their carotid arteries showed them to be free or nearly free of arterial plaque compared with a set of matched controls. Prior gene-chip studies at the University of California-Riverside (http://www.lef.or...01.html) in 2001 had already shown that calorie restriction begun in mid-life in mice partially reverses the age-related changes in 70% of the several hundred genes that change with aging. The Washington University Medical School study suggested that the same kinds of beneficial changes also occur in humans. In other words, calorie restriction begun later in life appears to dramatically improve your health, presumably reducing your risk of cancer (by a factor of 3:1 in mice), heart disease, diabetes, and possibly, Alzheimer's Disease (although not osteoporosis).

The Life Extension Foundation has sponsored other gene-chip studies that indicate that grape-seed-extract capsules (available at most supermarkets) and resveratrol capsules (100 mg.-to-250 mg. per day) yield changes in the 400-to-500 murine genes that alter with age that are similar to, but not entirely identical to those induced by calorie restriction. The diabetes drug, metformin (Glucophage), also effects rollbacks in aging-related genes that are similar to those attributable to calorie restriction.

It will probably be a while before several large-scale randomized placebo-controlled double-blind studies conducted over a period measured in decades can definitively determine how effective these early over-the-counter anti-aging strategies will be. In the meantime, some of us don't want to wait. As someone who has been calorie-restricted for 4½ years, and who has been taking resveratrol for 7 or 8 years, I can tell you that there have been no dramatic reversals in my appearance. On the other hand, my blood lipid profile has improved to the levels of a teenager, my fasting blood sugar has declined to 78 to 81 mg./dl., and the semiannual crops of pre-cancerous actinic keratoses that were a regular feature on top of my head have quit forming. I can't jump as high as I could 50 or 60 years ago, but I run a couple of miles a day. Otherwise, I feel the same way I did 50 or 60 years ago. Unfortunately, there aren't enough really old subjects in the Calorie Restriction Society to reach a conclusion regarding the demonstrated effectiveness of calorie restriction in extending human "health spans".

Argiod, the UN projects a peak global population of about 9 billion by 2060, followed by a slow population decline after that. In the meantime, some Western European countries such as France and Russia are facing declining populations and declining birth rates. It appears that women aren't enthused about having lots of children to rear. Concerning the potential impact of extending the human "youth span"... and the techniques I'm describing allow you to live longer by keeping you healthy longer..., calorie restriction reduces your fertility and libido, converting your growth and reproduction program to a repair and refurbishment program. However, if it allows people to live somewhat longer, it could eventually have some impact upon population. But life expectancies have risen from 47 years in 1900 to 77 years in 2000, even as family sizes dropped significantly, without disrupting society. If women could bear children for 100 years, we would probably have to address the question of population control, but perhaps it can be done--witness the Chinese one-child-per-family policy, and the Japanese restraint. Also, the majority of people polled feel, like DGBEACH, that they really don't want to live longer than 80 or so. Consequently, there may not be that large a fraction of the population that wants to live past 85.

With respect to the thesis that youth extension and aging reversal will be available only to the world's richest people, so far (insofar as I'm aware), that's not the case. I've wondered if there might be a multi-billionaire or a consortium of multi-billionaires secretly pursuing anti-aging strategies. I think a first step in combating such a scenario is getting out the word that serious age retardation and even partial age reversal may already be available over-the-counter--viz., to older members of your family. When the Washington University researchers announced their breakthrough discovery in April, 2004, I thought that this would trigger a global push to ameliorate aging in humans if only for its ability to reduce the risks of cancer, Type 2 diabetes, cardiovascular disease, and other degenerative diseases. We're talking about treatments that would hugely reduce health care costs. But although the news appeared in news media around the world, nothing further seemed to happen. In the meantime, some of us are beneficiaries of this knowledge, although there are probably a great many improvements that could be made, given public support. (Whew! I didn't plan to write all this.)

DGBEACH
1 / 5 (1) Mar 17, 2008
Also, the majority of people polled feel, like DGBEACH, that they really don't want to live longer than 80 or so. Consequently, there may not be that large a fraction of the population that wants to live past 85. .


I am 45 now, and I see how people in their 80's are treated, and the way they are forced to live. There would have to be an E-X-T-R-E-M-E change in public awareness and sensitivity to the suffering of the elderly before I could even entertain the thought of living longer than the current average.

I do thank you RN for sharing your knowledge, however, and this over-weight-middle-aged engineer will definately look into the things you've mentioned.
googleplex
not rated yet Apr 04, 2008
Thanks RN for your time, info and eloquence.