Researchers here report on the identification of a fairly direct link between the biochemistry of calorie restriction and a reduced accumulation of senescent cells, one of the root causes of aging. All aspects of aging are slowed somewhat by the practice of calorie restriction, though far less so in humans than is the case in short-lived mammals such as mice. Since calorie restriction changes near everything in the operation of cellular metabolism, finding the few important links between those changes and the mechanisms of aging has proven to be a slow and expensive task. Still, as this example demonstrates, evidence emerges eventually.
"As people become older, they are more susceptible to disease, like cancer, cardiovascular disease and Alzheimer's disease. Age is the most important so-called risk factor for human disease. How to actually delay aging is a major pathway to reducing the incident and severity of human disease. The most important part of aging is vascular aging. When people become older, the vessels that supply different organs are the most sensitive and more subject to aging damage, so studying vascular aging is very important. This study is focused on vascular aging, and in old age, what kind of changes happen and how to prevent vascular aging."
Researchers identified an important small molecule that is produced during fasting or calorie restriction conditions. The molecule, β-Hydroxybutyrate, is one type of a ketone body, or a water-soluble molecule that contains a ketone group and is produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diets, starvation, and prolonged intense exercise. "We found this compound, β-Hydroxybutyrate, can delay vascular aging. That's actually providing a chemical link between calorie restriction and fasting and the anti-aging effect. This compound can delay vascular aging through endothelial cells, which line the interior surface of blood vessels and lymphatic vessels. It can prevent one type of cell aging called senescence, or cellular aging."
Senescent cells can no longer multiple and divide. The researchers found β-Hydroxybutyrate can promote cell division and prevent cells from becoming senescent. Because this molecule is produced during calorie restriction or fasting, when people overeat or become obese this molecule is possibly suppressed, which would accelerate aging. In addition, the researchers found when β-Hydroxybutyrate binds to a certain RNA-binding protein, this increases activity of a stem cell factor called Octamer-binding transcriptional factor (Oct4) in vascular smooth muscle and endothelial cells in mice. Oct4 increases a key factor against DNA damage-induced senescence. "We think this is a very important discovery, and we are working on finding a new chemical that can mimic the effect of this ketone body's function."