A type of low-carb, low-calorie diet called “ketogenic diet” is rich in a compound that could delay the effects of ageing, scientists say.

Researchers in the laboratory of Gladstone Senior Investigator Eric Verdin, have identified the role that a chemical compound in the human body plays in the ageing process.

The mechanism may be key to new therapies for treating or preventing a variety of age-related diseases, including heart disease, Alzheimer’s and many forms of cancer.

Researchers examined the role of the compound beta-hydroxybutyrate (beta-OHB), a so-called “ketone body” produced during a prolonged low-calorie or ketogenic diet.

While ketone bodies such as beta-OHB can be toxic when present at very high concentrations in people with diseases such as Type I diabetes, researchers found that at lower concentrations, beta-OHB helps protect cells from “oxidative stress” -- which occurs as certain molecules build to toxic levels in the body and contributes to the ageing process.

“Here, we find that beta-OHB -- the body’s major source of energy during exercise or fasting -- blocks a class of enzymes that would otherwise promote oxidative stress, thus protecting cells from ageing,” Verdin said in a statement.

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 radicals -- leading to cell damage, oxidative stress and the effects of ageing. Researchers found that beta-OHB might actually help delay this process.

In a series of laboratory experiments, the team administered beta-OHB in a chronic calorie-restricted diet.

The researchers found that calorie restriction spurs beta-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 beta-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 signalling role for beta-OHB, but it could also represent a way to slow the detrimental effects of ageing 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 ageing and neurological disease,” said co-author Katerina Akassoglou.

“The findings could be relevant for a wide range of neurological conditions, such as Alzheimer’s, Parkinson’s, autism and traumatic brain injury-diseases that afflict millions and for which there are few treatment options,” Akassoglou said.

The study was published in the journal Science.

(This article was published on December 7, 2012)
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