Scientists have discovered a new role for a molecule produced during fasting: it can keep our vascular system supple and young.
The search for eternal youth has preoccupied the human imagination since the times of Ancient Greece.
In fact, a quick look at Greek mythology shows that youth was more prized than immortality, as some myths tell the story of how futile the latter is if it's not accompanied by the former.
In this regard, modern medicine has recently been catching up with ancient mythology.
Emerging scientific breakthroughs encourage us to hope that the myth of eternal youth will soon become a reality.
In a recent study, researchers were able to reverse signs of aging such as hair loss and wrinkles in mice; and, perhaps more impressively, another team of researchers managed to rejuvenate aging human cells.
Now, a new study adds to the evidence that aging can indeed be reversed. Scientists led by Dr. Ming-Hui Zou — the director of the Center for Molecular and Translational Medicine at Georgia State University in Atlanta — showed that fasting, or restricting calorie intake, can produce a molecule that delays vascular aging.
The findings were published in the journal Molecular Cell.
How a ketone molecule keeps cells young
Dr. Zou explains the motivation for this study, saying, "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."
So, the scientists set out to focus on vascular aging, on the changes that occur with senescence, and on ways to prevent them.
Specifically, the researchers looked at the link between calorie restriction and vascular aging. Dr. Zou used mouse models of atherosclerosis, studied their aortas post-mortem, and performed a series of cell culture experiments. They also induced starvation in the rodents and conducted similar tests.
They saw that, as expected, the starving mice produced the molecule beta-hydroxybutyrate. Surprisingly, however, this molecule also prevented vascular aging.
Beta-hydroxybutyrate is a ketone — that is, a molecule produced by the liver and used as an energy source when glucose is not available. The body produces ketones during fasting or starvation, on low-carb diets, and after prolonged exercise.
Interestingly, the research also revealed that beta-hydroxybutyrate promotes the division and multiplication of the cells that line the inside of blood vessels. Cellular division is a marker of cellular youth.
"We found [that beta-hydroxybutyrate] can delay vascular aging. That's actually providing a chemical link between calorie restriction and fasting and the anti-aging effect."
Dr. Ming-Hui Zou
"This compound can delay vascular aging through endothelial cells," Dr. Zou explains, "which line the interior surface of blood vessels and lymphatic vessels. It can prevent one type of cell aging called senescence, or cellular aging."
A drug target to stop aging, chronic disease
The study also revealed that the compound triggers another chain reaction that keeps the DNA of these endothelial cells young and undamaged.
More specifically, when beta-hydroxybutyrate attaches to the RNA-binding protein heterogeneous nuclear ribonucleoprotein A1, it boosts the activity of a stem cell transcriptional factor called Octamer-binding transcriptional factor (Oct4).
In turn, Oct4 "increases Lamin B1, a key factor against DNA damage-induced senescence," which keeps the blood vessels young.
"This stem cell factor (Oct4)," says Dr. Zou, "could be a pharmaceutical or pharmacological target for slowing down or preventing aging."
Dr. Ming-Hui Zou
"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," Dr. Zou adds.
"It's difficult to convince people not to eat for the next 24 hours to increase the concentration of this compound [...], 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."