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The scientists, whose work is published on March 25 in Nature Chemical Biology, also showed that the lifespan-extending cannabinoid pathway in C. elegans is related in unexpected ways to cannabinoid pathways found in humans and other mammals.
"This study reveals a new life-extension pathway, but more broadly, it introduces a powerful method for applying chemical probes to lab animals such as worms to discover biology that may be relevant to humans," says study senior author Benjamin Cravatt, PhD, Professor and Gilula Chair of Chemical Biology at Scripps Research.
Cravatt - Development - Proteomics - Methods - Enzymes
Cravatt is known for his development of advanced "chemical proteomics" methods for studying enzymes and the biological pathways they regulate. In the new study his team deployed these methods to investigate aging in C. elegans roundworms. The tiny worms normally live for just a few weeks -- compared to two or three years for lab mice -- making them, in principle, more practical for lifespan studies.
Lifespan studies using C. elegans worms typically involve the deletion or silencing of a particular gene in the embryonic stage of life to see if that extends the average lifespan of affected animals. The Cravatt team's approach, by contrast, was to use small-molecule compounds to disrupt enzyme-related pathways in adult worms, in the hope that this would uncover pathways that regulate lifespan.
Beauty - Approach - Compounds - Tools - Mechanisms
"The beauty of this approach is that any lifespan-extending compounds we identify can be useful tools to study whether the same mechanisms and targets also modulate aging in mammals," says study co-author Michael Petrascheck, PhD, associate professor in the Department of Molecular Medicine at Scripps Research.
The team used a library of about 100 such compounds, all known to inhibit enzymes called serine hydrolases in mammals. "Metabolic processes are very important in determining the rate of aging and lifespan, and serine hydrolases are major metabolic enzymes, so we thought...
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