A molecule produced by the body during
fasting or calorie restriction has anti-aging effects on the vascular
system, which could reduce the occurrence and severity of human diseases
related to blood vessels, such as cardiovascular disease, according to a
study led by Georgia State University.
“As people become older, they are more susceptible to disease, like
cancer, cardiovascular disease and Alzheimer’s disease,” said Dr.
Ming-Hui Zou, senior author of the study. “Age is the most important
so-called risk factor for human disease. How to actually delay aging is a
major pathway to reducing the incidence 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.
In their study, the research team explores the link between calorie
restriction (eating less or fasting) and delaying aging, which is
unknown and has been poorly studied. The findings are published in the
journal
Molecular Cell.
The 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.
The researchers reported that β-Hydroxybutyrate delays vascular aging by providing a chemical link between calorie restriction and fasting and the anti-aging effect.
This compound can delay vascular aging
of the endothelial cells, which line the interior surface of blood
vessels and lymphatic vessels, preventing a 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 these
cells from becoming old. 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.
Stem cell factor Oct4 increases a key factor against DNA damage-induced senescence, which can keep blood vessels young.
“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,” Zou said. “We’re trying to take the global approach to
reducing cardiovascular disease and Alzheimer’s disease.’
“It’s difficult to convince people not to eat for 24 hours to
increase the concentration of this compound (β-Hydroxybutyrate), and not
everybody can do that, but if we can find something that can mimic this
effect and people can still eat, it would make life more enjoyable and
help fight disease.
“This stem cell factor (Oct4) could be a pharmaceutical or
pharmacological target for slowing down or preventing aging. Then, if
the vascular system becomes younger, it is less likely to have
cardiovascular disease, Alzheimer’s disease and cancer because all of
these diseases are age-related.”
In the future, the researchers would like to target senescent cells
with the goal of eliminating them and rejuvenating the vascular system
to prevent cardiovascular disease.
The study is funded by the National Heart, Lung and Blood Institute of the National Institutes of Health.
