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Gene tweak that extends lifespan of fruit flies could help slow human aging

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December 15, 2011

The even distribution of different cell types seen in the intestinal tissues of young frui...

The even distribution of different cell types seen in the intestinal tissues of young fruit flies (left), breaks down as flies age (right) - researchers were able to delay this aging process by activating the dPGC-1 gene (Image: Salk Institute for Biological Studies)

Caloric restriction has been shown to slow the signs of aging and delay the development of age-related diseases in a wide range of animals. However, scientists have been unable to explain just why limiting daily food intake has such a beneficial effect on health and the biological mechanisms that underlie the phenomenon. Researchers in Sweden recently claimed to have unlocked a piece of the puzzle by identifying one of the enzymes that appears to play a major role in the process and now another group in the U.S. has provided another clue by tweaking a gene in fruit flies and extending their lifespan by as much as 50 percent.

While initial results are positive, due to the long lifespan of the species, studies on whether caloric intake works in nonhuman primates and humans are ongoing. Fruit flies, on the other hand, have a much shorter lifespan, with the ability to develop from egg to an adult in as little as seven days. This, along with numerous other reasons, has seen the fruit fly become a model organism that is widely used in studies of genetics and physiology.

A team consisting of researchers from the Salk Institute for Biological Studies and the University of California, Los Angeles, took the fruit fly ( (Drosophila melanogaster) and tweaked a gene in their intestinal stem cells known as dPGC-1, which is also found in human DNA and known as PGC-1. This resulted in the aging of the fruit flies' intestines being delayed and their lifespan being extended by as much as 50 percent.

In flies and mammals, the PGC-1 gene regulates the number of mitochondria within an animal's cells. Mitochondria are often referred to as "cellular power plants" because they convert sugars and fats from food into the energy for cellular functions. Since previous studies had shown that calorie-restricted animals have greater numbers of mitochondria in their cells, the researchers set about investigating what would happen when the PGC-1 is forced into overdrive.

Using genetic engineering techniques to boost the fruit fly equivalent of the PGC-1 gene resulted in the same kind of effects seen in organisms on calorie restricted diets - namely, greater numbers of mitochondria and more energy production. When the activity of the gene was accelerated in stem and progenitor cells of the flies' intestine, which serve to replenish intestinal tissues, these cellular changes corresponded with better health and longer lifespan.

Depending on the method and extent to which the activity of the gene was altered, the flies lived between 20 and 50 percent longer than normal.

The researchers say their findings suggest that the fruit fly version of PGC-1 can act as a biological dial for slowing the aging process and might serve as a target for drugs or other therapies to put the brakes on aging and age-related diseases. They theorize that boosting dPGC-1 stimulates the stem cells that replenish the intestinal tissues, thus keeping the flies' intestines healthier.

"Slowing the aging of a single, important organ - in this case the intestine - could have a dramatic effect on overall health and longevity," says Leanne Jones, an associate professor in Salk's Laboratory of Genetics and a lead scientist on the project. "In a disease that affects multiple tissues, for instance, you might focus on keeping one organ healthy, and to do that you might be able to utilize PGC-1."

The findings of the collaboration between the Salk Institute for Biological Studies and University of California, Los Angeles, researchers were published last month in Cell Metabolism.

About the Author
Darren Quick Darren's love of technology started in primary school with a Nintendo Game & Watch Donkey Kong (still functioning) and a Commodore VIC 20 computer (not still functioning). In high school he upgraded to a 286 PC, and he's been following Moore's law ever since. This love of technology continued through a number of university courses and crappy jobs until 2008, when his interests found a home at Gizmag.   All articles by Darren Quick
8 Comments

INEVITABILITY - BOON or BANE ?

David Nichols
16th December, 2011 @ 08:30 am PST

Old age and death cannot be stopped unless you can reprogram the genetic code in each of the trillions of cells in our bodies. Have fun with that one!

donwine
16th December, 2011 @ 09:22 am PST

Governments around the world cannot pay for the care of the older population now, if this came true it would never be allowed. We simply cannot afford to increase the number of living people on this planet.

John Hemingway Parkes
16th December, 2011 @ 11:52 am PST

David: you seem to have missed reading the articles' many points about the application of this knowledge. Drugs to target this gene could effect the same outcome, and while not mentioned in this article, certain natural chemicals are being explored by companies like Geron and Genentech which appear to emulate the effect of caloric restriction. One such substance is Resveratrol, to be specific.

Furthermore your supposition that every single cell in an organism would need this gene "switched on" is overly specious. As the target, in this article, is a single organ and only certain cells within that organ, a percentage of those cells could be quite sufficient to achieve life extending effects. Viruses that use reverse transcription manage to insert their dna packets into our genome all the time, and the same technique is used successfully in human gene therapy, so there is little reason to doubt the efficacy of this approach.

Lifespan HAS ALREADY in fact increased in our species due to a variety of manipulations of technology, including dietary understandings, nutritional access, safety improvements, medical intervention in pathologies, and more. Catch up with modern science, as the world seems to have passed you by.

brassservices
16th December, 2011 @ 01:09 pm PST

I am not a scientist.....but, life seems to find a way.....

Conditions on our earth are in continual flux and must have lead to a genetic disposition that would, over millions of years, have selected for a method to deal with these changing environments.

Life continues due to procreation but without food (and water) life ends abruptly.

If calories are restricted....it means food is not available, so starvation is prevalent which makes it necessary for those individuals who can survive to live longer.

When food is easily available, populations grow to the point where food again becomes scarce.

So, with respect to "natural selection" or "evolution" - well fed is a signal to our bodies to shorten life span and starving is a signal to increase life expectancy, all to promote the survival of "life" itself.

Bottom line...Drugs, or gene manipulation could very well over come the body's genetic propensities and offer us much longer lives.

I would argue not for endless life...but for, say, A doubling or even tripling of our life expectancy at a health level we enjoyed at 19 years of age. I don't want to be in the body of a 70 year old for another 140 years.

Then of course, there is the problem of population and sustainability.

This has been stated very clumsily, but does it make any sense??

No need to be kind

Xander66
17th December, 2011 @ 02:13 am PST

Hahahah.

You know this means you'll have to Work until you're 120. Hahaha

Matthew Jacobs
18th December, 2011 @ 06:02 pm PST

The actual issue is not a restriction of calories to achieve a longer life span, it's achieving the right balance between nutrients, protein and carbohydrates.

The genetic manipulation is merely an adjunct to this.

See this program - he and his teams are the ones working directly on these issues. It's available in video and audio for download.

You can research and cross reference much from this one lecture - and their research and other issues they refer too - it's complex and interwoven and very, very interesting.

Steve Simpson

Published 26 October 2010 | University of Sydney

Steve Simpson: Law of the Locust

http://www.abc.net.au/tv/bigideas/stories/2010/10/26/3047587.htm

Plagues of locusts have raised the ire of farmers at least since biblical times. But the breakthrough research from the University of Sydney's Professor Steve Simpson not only helps predict locust plagues, but has much to teach us about our own behavioural and dietary habits.

For instance: The "protein leverage" hypothesis that emerged from Professor Simpson's research shows that protein has the power to drive obesity and also to ameliorate it - a trend that holds true across a number of species, including humans.

Mr Stiffy
18th December, 2011 @ 06:04 pm PST

Taking care of the aged is a problem. It need not be. Just as we have many other problems, e.g., famine, decease, and war, they are quickly solved in a civilized world. Unfortunately, we are not yet civilized. When humankind overcomes superstition that will change, e.g., religion and government. Faith and force are destroying the world.

voluntaryist
19th December, 2011 @ 02:41 pm PST
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