Regional and Systemic Metabolic Remodeling Promotes Longevity by Bioengineered Yeast-Derived Lipids

Area of Science:

• Gerontology
• Metabolomics
• Molecular Biology

Background:

• Aging leads to declining intestinal integrity and metabolic homeostasis, impacting physiology and lifespan.
• Identifying interventions that promote healthy aging and extend lifespan is a critical area of research.

Purpose of the Study:

• To investigate the lifespan-extending effects of dietary lipids from a long-lived yeast strain in Drosophila.
• To elucidate the molecular and metabolic mechanisms underlying these effects.

Main Methods:

• Deuterium oxide-probed stimulated Raman scattering microscopy for metabolic imaging.
• Single nucleus RNA sequencing (scRNA-seq) for pathway analysis.
• Lipidomics and Raman spectroscopy for lipid characterization.

Main Results:

• Yeast lipids, enriched in saturated fatty acids and phospholipids, extend Drosophila lifespan.
• These lipids restore gut integrity by improving lipid metabolism and barrier function.
• Transcriptional changes in enterocytes include upregulated autophagy and reduced unsaturated fatty acid synthesis.
• Brain-specific effects involve energy conservation, enhanced signaling, and boosted mitochondrial function in Kenyon cells.
• Yeast lipids restructure gut metabolic modules for improved energy production and redox balance.

Conclusions:

• Dietary lipids from long-lived yeast offer a cross-kingdom approach to metabolic longevity.
• These yeast-derived components can support tissue homeostasis and promote healthy aging.