Summary of Detoxing Body of Harmful Fat By-Products To Extend Lifespan:
Scientists at the University of Virginia have identified a potential way to delay aging by detoxifying the body of glycerol and glyceraldehyde, harmful by-products of fat that naturally accumulate over time. The researchers discovered that they could prompt an anti-aging response by producing more of an enzyme, alcohol dehydrogenase, that prevents the toxicity caused by glycerol and, indirectly, glyceraldehyde. The researchers found that targeting these two toxic by-products of fat could help extend human lifespan by reducing the health-draining effects of the by-products. The findings have been published in the scientific journal Current Biology.
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Detoxifying harmful by-products of fat for healthy aging
As we age, our bodies accumulate harmful by-products of fat called glycerol and glyceraldehyde, which contribute to age-related diseases and lower lifespan. Scientists from the University of Virginia (UVA) have identified a potential approach to delay aging by detoxifying the body of these harmful by-products. Eyleen Jorgelina O’Rourke and her team have been studying the mechanisms behind healthy aging and longevity, and their recent findings suggest that reducing the health-draining effects of glycerol and glyceraldehyde could extend lifespan.
Unexpected discovery and mechanism
The scientists initially sought to activate autophagy, a cell-rejuvenating process, to extend lifespan. However, their work with microscopic worms, called C. elegans, surprisingly improved the worms’ health and lifespan by 50% without an increase in autophagy. They discovered that activating two enzymes, alcohol dehydrogenase and aldehyde-dehydrogenase, prevented the toxicity caused by glycerol and indirectly glyceraldehyde. They coined this mechanism AMAR, which stands for Alcohol and aldehyde-dehydrogenase Mediated Anti-aging Response. When they put the spurs to a particular gene, adh-1, by encouraging it to produce more alcohol dehydrogenase, the worms lived longer, healthier lives. In other models, such as yeast, the enzyme had similar beneficial effects on lifespan.
Findings in other models and implications for humans
As findings in lab models don’t always hold true in humans, the researchers investigated whether their lead was as promising as it appeared. They found that gene activity in creatures, including humans, who underwent fasting or calorie restriction, had increased levels of anti-aging enzymes. This suggests that AMAR could extend the number of years we live in good health and reduce age-related diseases, which are a major health burden for patients, families, and the healthcare system. Since glycerol and glyceraldehyde naturally increase over time, targeting AMAR could prevent fat-derived toxicity and help us shed extra weight.
Therapeutic implications and funding
The researchers aim to develop therapeutics that target AMAR, hoping to reduce the burden of age-related diseases and increase healthy, independent living for all. Their findings have been published in the scientific journal Current Biology. The research was supported by the National Institutes of Health, Pew Charitable Trusts, Jeffress Trust, W.M. Keck Foundation, Jefferson Scholars Foundation, and UVA’s Society of Fellows, Medical Scientist Training Program, and a cell and molecular biology training grant.
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