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Proteins link diet to longevity

Scientists have elucidated a key element of how diet restriction might boost life span. A single pair of proteins, whose activity is linked to diminished food intake, is responsible for significantly increasing the lifespan of worms, a linkurl:study;http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08130.html published in this week's __Nature__ reports. "[This study] is going to open a field that's probably going to be important for mammalian life," said gerontologist linkurl:Nir Ba

By | June 24, 2009

Scientists have elucidated a key element of how diet restriction might boost life span. A single pair of proteins, whose activity is linked to diminished food intake, is responsible for significantly increasing the lifespan of worms, a linkurl:study;http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08130.html published in this week's __Nature__ reports. "[This study] is going to open a field that's probably going to be important for mammalian life," said gerontologist linkurl:Nir Barzilai;http://molgen.aecom.yu.edu/index.php?option=com_content&task=view&id=45&Itemid=68 of the Albert Einstein College of Medicine in New York, who was not involved in the study. He cautioned that since the study was done in worms, its relevance to mammalian aging isn't yet clear. "It's not totally translatable, but it is exciting," he said.
__C. elegans__
Image: NGHRI
Scientists have been studying the phenomenon of increased longevity with diet restriction for about 70 years, and have replicated the effect in many species, from mice and fish to yeast and primates. But until about two years ago, when linkurl:Andrew Dillin;http://www.salk.edu/faculty/dillin.html of the Salk Institute for Biological Studies in La Jolla and his team linkurl:showed;http://www.ncbi.nlm.nih.gov/pubmed/17476212?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum that a transcription factor called PHA-4 (or FOXA in humans) was involved, little of the genetic mechanism behind the lifespan benefit had been revealed. The present study, also from Dillin's lab, elucidates upstream elements of the conserved pathway responsible for making diet restricted animals live longer. "It's sort of like a ladder," Dillin told __The Scientist__. "The bottom rung was FOXA, and now we've added on a few more rungs to the ladder." Most likely, caloric restriction causes longevity through some combination of genetic and environmental factors, with a reduced flow of nutrients into the body triggering genetic switches that lead to longer life, according to Barzilai. "Those are the switches [Dillin] is working on," Barzilai told __The Scientist__. "What Dillin is doing here is connecting the interaction between genes and the environment" in __Caenorhabditis elegans__. Dillin and his colleagues knew that eliminating a gene involved in protein degradation -- __wwp-1__ -- from the __C. elegans__ genome resulted in adult worms that were more vulnerable to environmental stresses. This led them to suspect that the gene and the enzyme for which it coded -- WWP-1 -- might play a role in longevity. They showed that mutating WWP-1 in diet-restricted __C. elegans__ could reduce the longer lifespans seen in diet restricted worms with normally functioning WWP-1. Preliminary studies suggested that another enzyme -- UBC-18 -- works in tandem with WWP-1 to produce this effect. "It was very surprising that this enzyme pair was so incredibly specific for the response to diet restriction," said Dillin. In humans, Dillin said, this enzyme pathway is conserved, so it may be possible to find compounds that alter the activity of these enzymes, essentially tricking the human body into thinking it is calorie-restricted under normal dietary conditions. That in turn could produce the longevity gains seen in calorie restricted individuals without the need for dieting. "WWP-1 and UBC-18 are both enzymes, so they give us good pharmacological targets to make small molecules to go after them," said Dillin. "You want to have some drug that will imitate caloric restriction, without us eating less," Barzai said, calling Dillin's findings "a natural step" towards this goal. Dillin and his colleagues elicited this exact effect in normally-fed __C. elegans__ when they over expressed WWP-1 and found that the worms lived 25% longer than normal. Dillin's lab is now searching for a receptor upstream of WWP-1 and UBC-18 that likely orchestrates the whole longevity/dietary-restriction pathway. His team is also searching for small molecules that target the two enzymes. "We may have some hints, but we don't have any homeruns yet," he said.
**__Related stories:__***linkurl:Longevity receptors;http://www.the-scientist.com/article/display/21045/
[24th January 2003]*linkurl:Uncovering the secret to human longevity;http://www.the-scientist.com/article/display/19870/
[31st August 2001]
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Comments

Avatar of: anonymous poster

anonymous poster

Posts: 4

June 24, 2009

"In humans, Dillin said, this enzyme pathway is conserved, so it may be possible to find compounds that alter the activity of these enzymes, essentially tricking the human body into thinking it is calorie-restricted under normal dietary conditions."\nIt is most likely possible. Why not? However, what will be the consequences? These genes are likely functioning as switches between catabolic and anabolic processes. (For example, one of the functions of FOXA is a regulation of glucose metabolism.) If we would "trick" our bodies to eat (catabolize) themselves under conditions of plentiful food supply, the least thing we might gain is a crazy high level of sugar in the blood. Just another way to get diabetes, not longevity. I would be glad to be mistaken about that, though.
Avatar of: anonymous poster

anonymous poster

Posts: 2

June 25, 2009

It is interesting that Bowhead whales, the longest living mammal, can live up to 200 years. They have more fat than almost any other animal.

June 27, 2009

I believe that if we tackle the genetic pathways involved in determining our life span - Its a bigger discovery than finding a cure for AIDS...\nI expect so many new gene therapy modalities to come into our everyday lives once we've got this core knowledge..\n\nI look forward to any updates in this field of research...
Avatar of: Ramesh Raghuvanshi

Ramesh Raghuvanshi

Posts: 20

June 27, 2009

From ancient time Hindu know this theory.Just read this proverb=====Reduce food half,Double the drinking water, triple mental and physical exercises and increase joy in your life fourth time.\n
Avatar of: anonymous poster

anonymous poster

Posts: 40

June 29, 2009

Recently we are being deluged with the results of a study showing that carrying a slight excess of weight is beneficial over being slender. What gives?

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