The effects of age and dietary restriction on the tissue-specific metabolome of Drosophila
Our first paper is from SAGE’s own Matt Laye (postdoc in the Kapahi lab), whose publication “The effects of age and dietary restriction on the tissue-specific metabolome of Drosophila” was just published in the journal Aging Cell. We asked Matt 10 questions about this paper.
1. How would you explain the main findings from this paper to the lay audience or say your grandmother?
We found that aging alters a large portion of all the metabolites in flies, and that dietary restriction could reverse the changes in these “aging” metabolites.
2. What’s the most significant finding from the paper?
We had two significant findings. First, dietary restriction reverses major changes to metabolites with aging (all of the metabolites of the fly). Second, dietary restriction increases the “connectiveness” of all the metabolites, while aging causes metabolite levels to be less connected to each other.
3. What were the technological or conceptual innovations from this study?
Conceptually we used a type of analysis called “Differential Coexpression Analysis”, which is a fancy way of saying that we examined not only how many different metabolites there were, but how those metabolites were connected to each other and whether those relationships changed with age or dietary restriction. Technologically, we used high resolution mass spectrometry, which means that we could detect over 30,000 unique metabolites in our samples, which is almost an order of magnitude more than most metabolomics studies.
4. How did you initiate the project?
We had been interested in finding out whether we could find specific metabolites that changed with age or dietary restriction which might eventually be used as a dietary supplement.
5. What was the role of your collaborators in the project?
Our collaborators played a huge role in this project. Daniel Promislow (University of Washington) was instrumental in the analysis and taking that analysis in novel directions. Dean Jones (Emory University) provides the technical expertise and machinery for the high resolution mass spectrometry approach.
6. What’s next after this paper for this field?
While we show that the relationship between metabolites changes with age and diet, we don’t know the biological significance of this yet. Future studies that address that question are certainly needed and will greatly enhance the biological relevance of our novel observations.
7. What were the major hurdles in completing this study?
The field of metabolomics struggles with the difficulty of determining what specific metabolite each of the 30,000 mass spectrometry peaks really is. We struggled with this as well and needed to verify that our putative metabolites are indeed what we thought they were using a different metabolomics platform.
8. What’s next for you after this study?
We are currently working on a paper describing how feeding one metabolite that increases in dietary restriction conditions can also increase lifespan in flies fed a nutrient rich diet.
9. How does the work relate to other findings from the lab or the Buck?
We have shown that dietary restriction is an effective way to increase lifespan in flies and that some of the increase in lifespan is due to changes in fat metabolism. This finding extends those observations by suggesting that other metabolites also help mediate the benefits of dietary restriction.
10. What is the “big picture” of your findings and how will they impact the field of aging research?
Dietary or caloric restriction is a robust way to alter every aspect of aging; genetically, cellularly, physiologically, metabolically, making it an attractive approach to find targets on how to prevent or delay aging.
Matthew Laye completed his undergraduate in Exercise Biology at University of California – Davis where he studied the effects of pollution on ventilatory function. He completed a PhD in Medical Physiology at University of Missouri with Dr. Frank Booth, during which he studied the effects of physical inactivity on metabolic dysfunction. From Missouri he went to Copenhagen and the Centre for Inflammation and Metabolism completing a post-doctoral fellowship researching the beneficial effects on exercise in humans at the cellular level. At the Buck Institute he has worked in the Kapahi lab studying the molecular mechanisms by which dietary restriction slows aging. He will start as an Assistant Professor at The College of Idaho in the Health and Human Performance Department this fall.
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