Gene clue to longevity uncovered

Gene clue to longevity uncovered

By Rebecca Morelle Science reporter, BBC News

The study was carried out on nematode worms

The mystery of how eating less boosts longevity is closer to being solved.

Studies have shown that severe calorie restriction markedly extends lifespan in mice and many other species - but the reasons for this remained elusive.

But now US research on nematode worms, published in Nature, has uncovered a gene linked to this unusual effect.

In the future, the find could lead to drugs that mimic the consequences of calorie restriction but negate the need for severe fasting regimes.

Sweet-spot

The life-lengthening properties of reducing calorie intake were first discovered in the 1930s, when laboratory rodents fed a severely reduced diet were found to outlive their well-fed peers.

Since then, this effect has been observed on organisms as diverse as yeast, flies, worms and dogs.

The consequences for humans of cutting calorie intake by about 60% while maintaining levels of vital nutrients are still unclear, although this extreme diet has a number of followers.

Andrew Dillin, an author of the paper and an associate professor at the Salk Institute for Biological Studies, said: "If you reduce food too much, you go towards starvation and live less long. If you overeat you will succumb to obesity and have a short lifespan. Dietary restriction is really a sweet-spot between the two.

"But for 72 years, we have not known how it works."

The scientists say mammals have a similar gene to pha-4

A study using nematode worms (Caenorhabditis elegans) revealed that a gene called pha-4 played a key role.

The team found worms that had their pha-4 genes removed showed no enhanced longevity while on the restricted diet.

But they discovered that the opposite experiment - over-expressing levels of pha-4 in the worms - increased longevity when on the restricted diet.

"This is the first gene we have found that is absolutely essential to the longevity response to dietary restriction," explained Dr Dillin.

"We finally have genetic evidence to unravel the underlying molecular programme required for increased longevity in response to calorie restriction."

Feast or famine

Although the study was carried out on worms, the finding could also be important for other species.

Mammals, including humans, possessed genes that were highly similar to the pha-4 gene, explained Dr Dillin.

Eat less, live longer?

These genes play a key role in development, and then in later life in the regulation of glucagon, a hormone that has a major role in maintaining glucose levels in blood - especially during fasting.

In fact, scientists believe the life-increasing effect of dietary restriction may be linked to boosting chances of survival through times of food scarcity.

"Pha-4 may be the primordial gene to help an animal overcome stressful conditions to live a long time through dietary restriction conditions," explained Dr Dillin.

Parallels?

Scientists now plan to look at the gene in other species.

Should the longevity link also apply to humans, it could open the door to the development of drugs that mimic the effects of calorie restriction while allowing people to maintain their normal diet, the scientists said.

Professor Richard Miller of the Institute of Gerontology at the University of Michigan, commented: "It is really hard to guess whether the connections that we see between the pha-4 system and calorie restriction in worms will have parallels in mammals, whose repertoire of responses to various forms of long- and short-term food shortages are far more complex than those of worms.

"But the Dillin paper provides both motivation to look and also clues about where to look. I think it's likely to be influential, even if the implications for mammals do eventually turn out to be a cul-de-sac - which they might or might not."

The Calorie Restriction Society - for people trying to live longer by eating fewer calories

Welcome to the Calorie Restriction (CR) Society

Our goal is to help people of all ages live longer and healthier lives simply by:

• eating fewer calories
• maintaining adequate nutrition

Since the 1930's extensive scientific research has shown that calorie restricted (CR) diets improve health and extend lifespans of nearly every species tested, including worms, spiders, rodents, dogs, cows and monkeys. We believe it is likely that people who carefully adopt a CR diet will see similar results.

The CR Society supports the efforts of people who practice CR for future longevity, current health, or other benefits; those curious about or interested in understanding the effects of the diet; and those interested in the development of related, science-based life-extension and health-enhancing technologies. Our mailing lists provide a rich forum for such topical discussions.

Calorie Restriction...the only proven life-extension method known to modern science.

reposted from: http://www.calorierestriction.org/Home
my highlights / emphasis / edits

The Scent of a Calorie: Whiff of Food Cancels Longevity from Caloric Restriction

February 01, 2007 The Scent of a Calorie: Whiff of Food Cancels Longevity from Caloric Restriction Diet-restricted fruit flies start acting like they are eating when they smell nutrients By Nikhil Swaminathan

reposted from: Scientific American
my highlights / emphasis / edits

Image: © STOCKBYTE/CORBIS LIFE-SHORTENING AROMA: In fruit flies, scientists have determined that the smell of food can have a negative effect on caloric restriction diets, generally designed to impart a longer life.

Evidence began mounting as long as 70 years ago that restricting calories while consuming necessary amounts of sustenance could increase one's life span. Since then, a group called the North Carolina-based Calorie Restriction Society has sprouted whose 1,800 members routinely down about half of the daily caloric intake recommended by the Food and Drug Administration (FDA) in the hope of living to the ripe old age of 120.

New research may prompt the organization to send out nose plugs with its next newsletter.

A team of scientists at the Baylor College of Medicine in Houston, New Mexico State University at Las Cruces and the University of Houston found that the average life span of fruit flies on restricted diets decreased when they were exposed to food odors. The findings, according to lead researcher Scott Pletcher of Baylor's Huffington Center on Aging, suggest that the flies are "actually perceiving the environment," thinking they are in a nutrient-rich place and then their bodies are "adaptively responding to it." The results imply there is likely some olfactory component affecting humans on caloric restriction diets as well.

Pletcher's group exposed two lab strains of fruit flies on caloric restriction to smells created by live yeast, an important constituent of the fly's diet. These flies died three to 10 days sooner—a 6 to 18 percent reduction in life span—than flies on the same diet that did not get a whiff of the yeast. Their life spans were further shortened if the flies actually ate the yeast paste.

Pletcher says the smell of yeast only had an effect on the life spans of dieting flies and not on those that were fully fed and likely already perceived their immediate environment to be nutrient-rich. "If you're in what might be considered an alternative physiological state that is associated with long life span under diet restriction, then the foods have some effect," he says, noting "that suggests that there's some interaction because the odorants aren't having the same effect in all environments."

To determine if smell alone has an effect on longevity, Pletcher's team created a fruit fly strain that had a particularly sensitive olfactory receptor inhibited. Fully fed female flies with an impaired sense of smell exhibited an average life span increase of 56 percent compared with unaltered wild females. Males also lived longer than their wild counterparts. Pletcher says this indicates that odor-mediated aging and dietary effects on aging probably share some of the same physiological pathways.

Brown University ecologist Marc Tatar says the current study, published in this week's Science, provides "really profound evidence" that longevity is controlled not by actual resources but rather by hormones that are cued to resources (such as the way plants sense winter by sunlight changes). "It's like the whole system doesn't actually function on the currency of resources anymore, it all functions on virtual data about what the resources should be like," he says. "It's mind over matter."

Pletcher agrees with that analysis, at least in part. "Some component is due to perception," he says, "and another large component is actually consumption." But given the effect that eating versus smelling yeast had on longevity, he says, "Overall, I would guess consumption has a bigger effect than perception, that's for sure."

RELATED LINKS: Being Cool Could Be the Key to a Longer Life Caloric Restriction and Aging How Low-Cal Diet Lengthens Fruit Fly Life Span Benefits of Diet Can Kick in Late in Life