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Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
Breakthrough suggests way to protect cells from damage caused by chronic disease
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 ?-hydroxybutyrate (?OHB), a so-called "ketone body" that is produced during a prolonged low-calorie or ketogenic diet. While ketone bodies such as ?OHB 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, ?OHB 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 ?OHBthe 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 ?OHB 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 ?OHB is administered during a chronic calorie-restricted diet. The researchers found that calorie restriction spurs ?OHB 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 ?OHB 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 ?OHB, 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 ?OHB 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 ?OHBespecially 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."
###
Matthew Hirschey, PhD; John Newman, MD, PhD; Wenjuan He, PhD; Kotaro Shirakawa, PhD; Natacha Le Moan, PhD; Carrie Grueter, PhD; Hyungwook Lim, PhD; Laura Saunders, PhD; Robert V. Farese, Jr., MD; and Katerina Akassoglou, PhD, also participated in this research at Gladstone. This research was supported by the Gladstone Institutes.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
[ | E-mail | Share ]
Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
Breakthrough suggests way to protect cells from damage caused by chronic disease
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 ?-hydroxybutyrate (?OHB), a so-called "ketone body" that is produced during a prolonged low-calorie or ketogenic diet. While ketone bodies such as ?OHB 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, ?OHB 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 ?OHBthe 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 ?OHB 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 ?OHB is administered during a chronic calorie-restricted diet. The researchers found that calorie restriction spurs ?OHB 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 ?OHB 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 ?OHB, 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 ?OHB 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 ?OHBespecially 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."
###
Matthew Hirschey, PhD; John Newman, MD, PhD; Wenjuan He, PhD; Kotaro Shirakawa, PhD; Natacha Le Moan, PhD; Carrie Grueter, PhD; Hyungwook Lim, PhD; Laura Saunders, PhD; Robert V. Farese, Jr., MD; and Katerina Akassoglou, PhD, also participated in this research at Gladstone. This research was supported by the Gladstone Institutes.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2012-12/gi-gsd120512.php
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