Buck Institute’s Innovative Approach to Lifespan Research: Insights from Fruit Flies to Humans

Traditional approaches to understanding human aging involve testing compounds on fruit flies and mice—a process that can be both costly and time-consuming. However, scientists at the Buck Institute for Research on Aging have leapfrogged this standard approach using advanced machine learning and systems biology to analyze large-scale data from both flies and humans. This new method, detailed in a *Nature Communications* publication, has already revealed significant findings, including the potential of threonine, an essential amino acid, as a candidate for therapeutic interventions to promote healthy aging. 

“This would not have been possible without this pioneering approach,” said Pankaj Kapahi, PhD, a senior author on the study. “There is a lot of data sitting out there that is not being correlated between species. I think this approach could be a game-changer when it comes to identifying potential interventions to improve human health.”

Threonine and Health Benefits

Threonine, already known to protect against diabetes in mice, has shown promise in this study for promoting longevity and healthspan. Threonine contributes to essential functions like collagen and elastin production, blood clotting, fat metabolism, and immune response. When tested, the amino acid extended the lifespan of flies, but the effects varied based on specific genetic and biological traits, hinting at its potential for personalized medicine approaches.

Data-Driven Approach: How the Study Worked

The study began with Tyler Hilsabeck, PhD, a former postdoc at the Buck Institute, who analyzed metabolomic, phenotypic, and genomic data from 160 fruit fly strains on both restricted and regular diets, evaluating over 120 metabolites. “This allowed us to find the ‘needles in the haystack’ in terms of identifying metabolites that might impact lifespan and healthspan,” Hilsabeck explains.

Following this, postdoctoral fellow Vikram Narayan, PhD, cross-referenced the fly data with human data from the extensive UK Biobank. This cross-species comparison identified common metabolites with similar effects, including threonine, which appeared beneficial, and orotate, which was associated with shorter lifespan. The team further tested these metabolites in flies, confirming the initial findings.

Key Findings and Larger Implications

The research found that threonine extended lifespan in a strain-specific way, showing potential in both flies and humans. However, not all results were positive: Orotate, a metabolite linked to fat metabolism, counteracted lifespan extension benefits in flies on restricted diets and correlated with shorter lifespans in humans.

"We’re not saying threonine will work in all conditions," Kapahi clarifies. "Our research shows it works in subsets of both flies and people. We no longer expect a 'magic-bullet' solution for aging, and our method offers a precision approach to geroscience.”

Kapahi is hopeful that the wider scientific community will adopt this methodology, reducing the need for mice studies and advancing basic aging research. "Many promising findings in flies and worms don’t make it to human studies due to limited resources. This approach allows us to prioritize discoveries likely to benefit humans,” he said.