Is it possible that the same enzyme that helps us get rid of alcohol can also help us live longer and healthier lives? Scientists have uncovered a molecular mechanism that may be able to do just that.
Researchers at the University of Virginia (UVA) discovered that the role of alcohol dehydrogenase in detoxifying the body of glycerol and glyceraldehyde – the toxic byproducts of fat that accumulate over time – might be the best way to not just extend life but also age more healthily.
“The discovery was unexpected,” said Eyleen Jorgelina O’Rourke, Associate Professor in the Departments of Biology and Cell Biology at the University of Virginia. “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.”
AMAR
The method was named AMAR (alcohol or aldehyde mediated anti-aging response), which is also the Sanskrit term for immortality when the investigators observed unexpected results by activating the adh-1 gene. It resulted in the gene creating more alcohol dehydrogenase enzymes, which prevented glycerol and, indirectly, glyceraldehyde toxicity.
Activating this AMAR mechanism in Caenorhabditis elegans demonstrated that the microscopic worms not only lived 50 percent longer but showed better health.
The two-to-three-week lifespan of the minuscule soil-dwelling worms provides scientists with measurable results, and they share more than 70 percent of human genetic composition. Scientists have previously increased their longevity by blocking a specific enzyme, observed positive results with a mixture of medications, investigated the gut-brain interaction with aging, and utilized them to investigate why immortality is so difficult.
The team discovered that the anti-aging mechanism had a comparable effect on yeast, a second laboratory subject. They then looked at studies on others, including humans, who had gone through fasting or calorie restriction, both of which are known to help people live longer and healthier lives.
“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.
Breaking down toxic buildup
Experts believe that because glycerol and glyceraldehyde are toxic, health-draining byproducts of fat that we accumulate more of as we age, they may play a role in us developing more health problems over time. AMAR may counteract and break down the buildup of toxic byproducts, resulting in long years of excellent health. Furthermore, activation of adh-1 shows the ability to counteract weight gain and even promote weight loss.
“We see this response across species, from yeast to high plants and humans,” O’Rourke explained to New Atlas. “Activating adh-1 promotes leanness, even when animals are eating as much as they want.”
The researchers plan to explore if genetic activation of the enzyme improves the lifespan of mice, followed by in vitro study with human-grown cells to see if activation of adh-1 decreases or delays biological indicators 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.”
Source study: Current Biology— Increased alcohol dehydrogenase 1 activity promotes longevity
