Fatty acids and glycerol, key byproducts of fat metabolism, are increasingly recognized as significant contributors to ageing and chronic diseases. Research suggests that reducing these byproducts, particularly through the enzyme ADH-1, could slow the ageing process. Both calorie restriction and drugs like rapamycin have been shown to increase ADH-1 activity, leading to lower glycerol levels and extended lifespans in lab animals.
The impact of fat byproducts on ageing
As people age, an unavoidable increase in body fat occurs. While much of society focuses on the aesthetics of being overweight, medical professionals emphasize the health implications of fat byproducts in the body. Fatty acids are essential for various bodily functions, but excessive amounts can be harmful, shortening a person’s health span and life span by increasing their risk of chronic diseases, disrupting metabolic processes, and promoting inflammation. Although fatty acids are routinely checked during medical examinations, the other key component of fat, glycerol, is often overlooked despite its potentially harmful effects.
Both fatty acids and glycerol disrupt cellular and organ function, mirroring the effects of ageing. Obesity is increasingly seen as a catalyst for accelerated ageing.
Research focus on fat and ageing
The role that fats play in ageing is a primary focus for genomicist and biochemist Eyleen Jorgelina O’Rourke, Associate Professor of Biology and Cell Biology at the University of Virginia. Her research team investigates whether reducing harmful fat byproducts might help slow the ageing process and stave off common diseases.
Breaking down fat byproducts
In their studies aimed at extending the lifespan and improving health in older lab animals, O’Rourke and her colleagues found a consistent pattern: all the anti-ageing interventions tested led to reduced glycerol levels. For example, the nematode Caenorhabditis elegans lives about 40% longer on a calorie-restricted diet. These long-lived worms had lower glycerol levels compared to their shorter-lived counterparts who were not food restricted. Calorie restriction also heightened the activity of the enzyme responsible for breaking down glycerol, ADH-1, in their intestine and muscles.
ADH-1 and calorie restriction
Similar high ADH-1 activity levels were observed in people undergoing dietary restriction or treated with the anti-ageing drug rapamycin. This suggests a common mechanism underlying healthy ageing across species, with ADH-1 at its core. Elevated ADH-1 activity is hypothesized to promote health in old age by decreasing harmful glycerol levels.
Supporting this hypothesis, researchers found that adding glycerol to the diet of worms shortened their lifespan by 30%. In contrast, animals genetically modified to boost levels of the glycerol-busting enzyme ADH-1 had low glycerol levels and remained lean and healthy with longer lives, even on unrestricted diets. The simple molecular structure and extensive research on ADH-1 make it an attractive target for developing drugs that boost its activity. O’Rourke’s lab aims to explore how compounds that activate ADH-1 affect the health and longevity of both mice and humans.
Societal implications of anti-aging research
Anti-ageing research generates both excitement and debate. The benefits of healthy ageing are clear, but extending lifespan through healthier ageing will likely introduce new societal challenges. If lifespans extending to 120 years become the norm, social structures, including retirement ages and economic models, will need to evolve to accommodate an ageing population. Legal and social frameworks regarding the elderly and family care may need revision. The sandwich generation—those with children and living parents and grandparents—might find themselves caring for even more generations simultaneously. Longer lives will require society to rethink and reshape how we integrate and support an increasingly older population.
Whether through ADH-1 or dietary adjustments, the quest for the solution to healthy ageing is not just a medical journey but a societal one.
Adapted from an article originally published in The Conversation.
