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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2015-01-12T00:00:00-05:00" class="date-display-single">January 12, 2015</span></p><div class='syndicate'><h1>Pathways Underlying the Benefits of Calorie Restriction</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul class="spaced">
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<li>A mouse study revealed that some of the health benefits of calorie restriction are due to increased production of the gas hydrogen sulfide.</li>
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<li>The key metabolic pathways exist in yeast, worms, flies, and mice, suggesting they are highly conserved and could have potential clinical applications.</li>
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<picture title="Hydrogen sulfide molecules">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2015/20150112-calorie.jpg?itok=QhxEUJHl&timestamp=1431010904 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2015/20150112-calorie.jpg?itok=NchwamvN&timestamp=1431010904 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2015/20150112-calorie.jpg?itok=CLKTvEXV&timestamp=1431010904 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2015/20150112-calorie.jpg?itok=jCwms5L8&timestamp=1431010904 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2015/20150112-calorie.jpg?itok=HDhJ6Q3f&timestamp=1431010904 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2015/20150112-calorie.jpg?itok=NchwamvN&timestamp=1431010904" alt="Hydrogen sulfide molecules." title="Hydrogen sulfide molecules" />
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</picture><span class="caption">Calorie restriction leads to increased production of the gas hydrogen sulfide.</span></div>
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</div><p>Calorie restriction is the process of reducing food intake—typically by at least 30% from a normal diet—without malnutrition. Researchers have known since the 1930’s that this regimen, also referred to as dietary restriction, has numerous health benefits. It can extend the lifespan of yeast, worms, flies, and some mice. Calorie restriction can also improve tolerance to certain metabolic stresses to the body.</p>
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||
<p>A team led by Drs. Christopher Hine and James Mitchell at the Harvard School of Public Health set out to determine the molecular mechanisms by which calorie restriction can bring health benefits. The study was funded in part by NIH’s National Institute on Aging (NIA), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Cancer Institute (NCI). Results appeared online on December 23, 2014, in <em>Cell.</em></p>
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||
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||
<p>The researchers induced surgical stress in mice by temporarily halting blood flow to the liver. When blood flow is restored to the tissue, it shows damage and inflammation. This injury model, known as ischemia reperfusion, is similar to what occurs during organ transplantation, stroke, or heart attack in humans.</p>
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||
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<p>The team found that mice that had their diet restricted by 50% for a week before the surgery showed less liver damage than mice provided with unlimited food. The beneficial effects of the calorie restriction could be blocked, however, by providing the mice with extra methionine and cysteine. These 2 amino acids are notable because they both contain sulfur.</p>
|
||
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||
<p>The scientists determined that restricting these 2 sulfur-containing amino acids activated a metabolic pathway called the transsulfuration pathway, which resulted in increased production of the gas hydrogen sulfide (H<sub>2</sub>S). When they deleted a gene for an H<sub>2</sub>S-producing enzyme in mice, the protective effects of dietary restriction were lost. Conversely, mice genetically manipulated to make more of the gas had less surgical damage, even without dietary intervention. Thus, production of the gas was important for the benefits of calorie restriction against surgical stress.</p>
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|
||
<p>Further experiments showed that H<sub>2</sub>S production played a role in calorie-restricted models of longevity in yeast, worms, fruit flies, and mice. This implicates an evolutionarily conserved metabolic pathway in several of the benefits of calorie restriction.</p>
|
||
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||
<p>“This finding suggests that H<sub>2</sub>S is one of the key molecules responsible for the benefits of dietary restriction in mammals and lower organisms as well,” Mitchell says. “While more experiments are required to understand how H<sub>2</sub>S exerts its beneficial effects, it does give us a new perspective on which molecular players to target therapeutically in our efforts to combat human disease and aging.”</p>
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<p>—by Carol Torgan, Ph.D.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/protein-consumption-linked-longevity" target="_top">Protein Consumption Linked to Longevity</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/how-resveratrol-may-fight-aging" target="_top">How Resveratrol May Fight Aging</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/calorie-restriction-may-not-extend-life" target="_top">Calorie Restriction May Not Extend Life</a></li><li><a href="https://www.nia.nih.gov/health/publication/metabolism-does-stress-really-shorten-your-life/does-how-much-you-eat-affect-how" target="_top">Biology of Aging: Does How Much You Eat Affect How Long You Live?</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/25542313">Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits.</a> Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Treviño-Villarreal JH, Mejia P, Ozaki CK, Wang R, Gladyshev VN, Madeo F, Mair WB, Mitchell JR. <em>Cell.</em> 2014 Dec 23. pii: S0092-8674(14)01525-6. doi: 10.1016/j.cell.2014.11.048. [Epub ahead of print]. PMID: 25542313.
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</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute on Aging (NIA), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Cancer Institute (NCI); Glenn Foundation; Austrian Science Fund; American Heart Association; and the Canadian Institutes of Health Research.</p>
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<div about="/block/research-matters---popular-stori" class="ds-1col entity entity-bean bean-research-matters-block view-mode-default clearfix">
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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||
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||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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</div>
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<h3 class="block__title">About NIH Research Matters</h3>
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<div about="/block/research-matters---about" class="ds-1col entity entity-bean bean-research-matters-block view-mode-default clearfix">
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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