Navigation Links
Gladstone scientists discover novel mechanism by which calorie restriction influences longevity
Date:12/6/2012

SAN FRANCISCO, CADecember 6, 2012Scientists at the Gladstone Institutes have identified a novel mechanism by which a type of low-carb, low-calorie dietcalled a "ketogenic diet"could delay the effects of aging. This fundamental discovery reveals how such a diet could slow the aging process and may one day allow scientists to better treat or prevent age-related diseases, including heart disease, Alzheimer's disease and many forms of cancer.

As the aging population continues to grow, age-related illnesses have become increasingly common. Already in the United States, nearly one in six people are over the age of 65. Heart disease continues to be the nation's number one killer, with cancer and Alzheimer's close behind. Such diseases place tremendous strain on patients, families and our healthcare system. But today, researchers in the laboratory of Gladstone Senior Investigator Eric Verdin, MD, have identified the role that a chemical compound in the human body plays in the aging processand which may be key to new therapies for treating or preventing a variety of age-related diseases.

In the latest issue of the journal Science, available online today, Dr. Verdin and his team examined the role of the compound β-hydroxybutyrate (βOHB), a so-called "ketone body" that is produced during a prolonged low-calorie or ketogenic diet. While ketone bodies such as βOHB can be toxic when present at very high concentrations in people with diseases such as Type I diabetes, Dr. Verdin and colleagues found that at lower concentrations, βOHB helps protect cells from "oxidative stress"which occurs as certain molecules build to toxic levels in the body and contributes to the aging process.

"Over the years, studies have found that restricting calories slows aging and increases longevityhowever the mechanism of this effect has remained elusive" Dr. Verdin said. Dr. Verdin, the paper's senior author, directs the Center for HIV & Aging at Gladstone and is also a professor at the University of California, San Francisco, with which Gladstone is affiliated. "Here, we find that βOHBthe body's major source of energy during exercise or fastingblocks a class of enzymes that would otherwise promote oxidative stress, thus protecting cells from aging."

Oxidative stress occurs as cells use oxygen to produce energy, but this activity also releases other potentially toxic molecules, known as free radicals. As cells age, they become less effective in clearing these free radicalsleading to cell damage, oxidative stress and the effects of aging.

However, Dr. Verdin and his team found that βOHB might actually help delay this process. In a series of laboratory experimentsfirst in human cells in a dish and then in tissues taken from micethe team monitored the biochemical changes that occur when βOHB is administered during a chronic calorie-restricted diet. The researchers found that calorie restriction spurs βOHB production, which blocked the activity of a class of enzymes called histone deacetylases, or HDACs.

Normally HDACs keep a pair of genes, called Foxo3a and Mt2, switched off. But increased levels of βOHB block the HDACs from doing so, which by default activates the two genes. Once activated, these genes kick-start a process that helps cells resist oxidative stress. This discovery not only identifies a novel signaling role for βOHB, but it could also represent a way to slow the detrimental effects of aging in all cells of the body.

"This breakthrough also greatly advances our understanding of the underlying mechanism behind HDACs, which had already been known to be involved in aging and neurological disease," said Gladstone Investigator Katerina Akassoglou, PhD, an expert in neurological diseases and one of the paper's co-authors. "The findings could be relevant for a wide range of neurological conditions, such as Alzheimer's, Parkinson's, autism and traumatic brain injurydiseases that afflict millions and for which there are few treatment options."

"Identifying βOHB as a link between caloric restriction and protection from oxidative stress opens up a variety of new avenues to researchers for combating disease," said Tadahiro Shimazu, a Gladstone postdoctoral fellow and the paper's lead author. "In the future, we will continue to explore the role of βOHBespecially how it affects the body's other organs, such as the heart or brainto confirm whether the compound's protective effects can be applied throughout the body."


'/>"/>

Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
Source:Eurekalert  

Related biology news :

1. ALS TDI and Gladstone Institutes collaborate to discover potential ALS treatments
2. Gladstone, Stanford scientists block toxic protein that plays key role in Lou Gehrigs disease
3. Gladstone scientists identify critical process in stem cell development
4. Gladstone scientist Warner C. Greene receives Washington University School of Medicine Alumni Award
5. Neuroscientists prove ultrasound can be tweaked to stimulate different sensations
6. New test adds to scientists understanding of Earths history, resources
7. 23andMe scientists receive more than $500,000 in National Institutes of Health funding
8. Salk scientists develop faster, safer method for producing stem cells
9. Kansas State University scientists named American Association for the Advancement of Science fellows
10. Liverpool scientists decipher genetic code of wheat
11. USDA scientists and cooperators sequence the wheat genome in breakthrough for global food security
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Gladstone scientists discover novel mechanism by which calorie restriction influences longevity
(Date:12/7/2016)... , Dec. 7, 2016   Avanade is ... Formula One teams in history, exploit biometric data in ... performance and maintain the competitive edge against their rivals ... Avanade has worked with Williams during ... of biometric data (heart rate, breathing rate, temperature and ...
(Date:12/5/2016)... , Dec. 5, 2016  The Office of ... published "Can CT Scans Enhance or Replace Medico ... potential of supporting or replacing forensic autopsies with ... scan. In response to recommendations made ... exploring using CT scans as a potential component ...
(Date:11/29/2016)... , Nov. 29, 2016 BioDirection, a privately ... products for the objective detection of concussion and other ... has successfully completed a meeting with the U.S. Food ... blood test Pre-Submission Package. During the meeting company representatives ... as a precursor to commencement of a planned pilot ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... , ... December 08, 2016 ... ... the commercial launch of flexible packaging for their exceptionally efficient human mesenchymal ... system extends RoosterBio’s portfolio of bioprocess media products engineered to radically streamline ...
(Date:12/8/2016)... , Dec. 8, 2016  HedgePath Pharmaceuticals, ... that discovers, develops and plans to commercialize innovative ... shares of common stock were approved for trading ... begin trading on the OTCQX, effective today, under ... for the OTCQX market, companies must meet high ...
(Date:12/7/2016)... ... December 07, 2016 , ... ACEA Biosciences, Inc. ... and expansion clinical trial for its lead drug candidate, AC0010, at the World ... trial was to determine the safety, antitumor activity, and recommended phase II dosage ...
(Date:12/7/2016)... , Dec. 7, 2016 /PRNewswire/ - Zenith Capital Corp. ("Zenith" or ... will be presented at the Company,s Annual and Special Meeting. ... Shareholders will take place on Thursday, December 15, 2016 at ... Hall (Room EC1040), 4825 Mount Royal Gate SW, ... A notice of meeting and management information circular, containing the ...
Breaking Biology Technology: