Scientists identify Longevity molecule produced by fasting

Going on a fasting diet could trim your waistline AND extend your life by slowing and reversing cardiovascular decline.

People have been dieting for decades, but researchers have discovered that fasting could put people on the fast-track to long life.

Longevity.Technology: We are excited by this research; being able to understand senescent cells, counter their harmful effects and exploit their benefits underpins Longevity research.

The TRL score for this Longevity.Technology domain is currently set at: ‘Technology refined and ready for initial human trials.’

The TRL score for the technology addressed in this article is: ‘Early proof of concept demonstrated in the laboratory.’

When the body fasts, or subsists on a diet low in energy-rich carbohydrates, it enters a metabolic state called ketosis. Since the body is no longer ingesting enough energy, it begins to use its fat reserves, converting them into ketones, molecules produced by the liver from fatty acids that can be used as a fuel source. One of these ketones is a molecule called β-Hydroxybutyrate and it is this molecule that has caused excitement in the Longevity field.

Β-Hydroxybutyrate has the ability to inhibit cell senescence – both senescence that results from a cell having achieved its maximum number of replications and senescence that occurs prematurely due to cell stress [1]. β-Hydroxybutyrate is able to put the brakes on vascular cell aging at a part of the cell cycle that means cell division is actively promoted [2].

Lead researcher of the Georgia State University study, Dr Ming-Hui Zou said: “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 [3].”

Β-Hydroxybutyrate also has another function in the Longevity battle; it triggers a chain-reaction by attaching to the RNA-binding protein heterogeneous nuclear ribonucleoprotein A1. This has the effect of boosting the activity of Octamer-binding transcriptional factor (Oct4), a stem cell transcriptional factor that can reprogram cells back to a pluripotent state and maintain that pluripotency [4]. Oct4 also increases the amounts of Lamin B1, a key factor in preventing DNA damage-induced senescence [5]; this has the effect of keeping the blood vessels young.

Dr Zou added: “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 … 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 [6].”

The research team plans to further develop their work on senescence cells to see if they can be eliminated; this would have the effect of rejuvenating the vascular system and preventing cardiovascular disease.