Using a lipidomics approach to analyze the role of sphingomyelin in aging in C. elegans

Abstract

Research breakthroughs on aging and diseases have helped extend life expectancy in the United States over the last 25 years. However, as individuals continue to age, they lose the ability to perform motor and cognitive functions and their risk of developing chronic diseases increases. Here, we used a lipidomic approach to identify important lipid mediators of aging in C. elegans. This study focuses on the bioactive lipid sphingomyelin (SM), whose abundance depends on metabolic enzymes including acid sphingomyelinase (ASM). In C. elegans, one ASM ortholog is coded by the asm‐3 gene, and loss of asm‐3 extends lifespan in C. elegans. To explore longitudinal changes in lipids between wildtype (wt) and mutant asm‐3 C. elegans during aging, we collected six samples of wt and asm‐3 animals, at ages 1, 5, and 10 days, for lipid analysis. Approximately 700 different lipids were abundant enough in concentration for analysis. We found that 10‐day old asm‐3 mutants have increased levels of two Omega‐3 fatty acids, docosahexaenoic acid (DHA/22:6) and docosapentaenoic acid (DPA/22:5); both are linked to increased lifespans and decreased mortality when present in higher concentrations. Previous studies show that SM accumulates later in life causing aging to accelerate, but less is known regarding changes in specific types of sphingomyelin. Therefore, we also sought to examine how chain length and saturation levels of SM change with age by comparing the SM of 1 and 10 day old wt worms. Future work plans to correlate lipid composition to physiological changes in old animals. Together, we hope that we can better understand the intrinsic biochemical lipid processes associated with late life conditions to better prevent illness care for our aging populations.Support or Funding InformationResearch reported in this publication was supported by the National Institute On Aging of the National Institutes of Health under Award Number R15AG052933. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.