Wednesday 15 March 2023

Wonder enzyme may hold the key to longer, healthier lives


Could an enzyme responsible for breaking down and eliminating booze from our bodies also be able to help us lead longer, healthier lives? Scientists have discovered a molecular mechanism that could offer just that.

In a surprise finding, researchers at the University of Virginia (UVA) found that the role of alcohol dehydrogenase in detoxifying the body of glycerol and glyceraldehyde – the harmful by-products of fat that build up over time – may provide the best approach to not just extending life but aging more healthily.

“The discovery was unexpected,” said Eyleen Jorgelina O’Rourke, Associate Professor at UVA’s Department of Biology and the UVA School of Medicine’s Department of Cell Biology. “We went after a very well-supported hypothesis that the secret to longevity was the activation of a cell-rejuvenating process named autophagy and ended up finding an unrecognized mechanism of health and lifespan extension.”

Naming the mechanism AMAR (alcohol or aldehyde mediated anti-aging response), which is also the Sanskrit word for immortality, the scientists saw surprising responses by activating the adh-1 gene. It resulted in the gene producing more of the alcohol dehydrogenase enzymes, blocking the toxicity caused by glycerol and, indirectly, glyceraldehyde.

In Caenorhabditis elegans, activating this AMAR mechanism showed the microscopic worms not only lived 50% longer but had better health signs, too.

C. elegans are the preferred model for aging studies; the microscopic soil-dwelling worms’ two-to-three-week lifespan offers scientists measurable results, and they share more than 70% of our genetic makeup. Previously scientists have extended their lifespan by blocking a particular enzyme, seen positive results with a cocktail of drugsexplored the gut-brain relationship with aging, and used them to look at why immortality is so elusive.

The team then found that the anti-aging mechanism had a similar benefit on another lab subject, yeast. They then looked at studies on others, including humans, that had undergone fasting or calorie restriction, both understood to play a role in living longer and healthier.

“Another exciting moment was when we mined the gene activities of calorically restricted mice, pigs, Rhesus monkeys, and humans, and saw that their adh-1 was activated,” O’Rourke told New Atlas.

Scientists suspect that because glycerol and glyceraldehyde are toxic, health-draining by-products of fat, and that we store more as we age, they could be contributing factors in us experiencing more health issues over time. AMAR may combat and break down the build-up of the harmful by-products, leading to more years of good health. What’s more, the activation of adh-1 showed an ability to counter weight gain and even promote weight loss.

“In fact, we see this response across species from yeast to high plants and humans,” O’Rourke told New Atlas. “Activating adh-1 promotes leanness, even when animals are eating as much as they want.”

The team expects to now test if genetic activation of the enzyme extends the lifespan of mice, and then conduct in vitro research with human cultured cells to examine if activation of adh-1 reduces or delays the cellular markers of aging.

“We are hoping to identify partners (academic or private) to search together for compounds that activate the alcohol and/or the aldehyde dehydrogenase,” she told New Atlas. “We are eager to perform these searches for activators because we see that the activation of these enzymes not only extends lifespan but it also reduces the severity and delays the onset of age-related diseases including obesity, loss of muscle function, and neurodegeneration.”

The study was published in the journal Current Biology.

Source: University of Virginia/New Atlas

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