Sphingolipids are bioactive lipid molecules involved in cell proliferation, growth, survival, and death. In particular, the sphingolipids ceramide and sphingosine are thought to mediate cell death signaling whereas their phosphorylated counterparts, ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P), are thought to mediate cell survival signaling. Regulation of these molecules is mediated by the lipid enzymes ceramide kinase and sphingosine kinase, respectively. Misregulation of the enzymes can alter the balance between the lipids, and impact cell survival and animal health. Indeed, aging tissues contain increased sphingosine and ceramide but decreased levels of S1P. To examine the mechanisms by which sphingolipids mediate aging, we examined life history, aging and healthspan traits of C. elegans mutants for sphingolipid enzymes. We focused on the response of aging animals to oxidative and heat stress. We found that sphingosine kinase (
sphk-1) mutants, which cannot produce S1P, have shorter lifespan, brood size, and body size compared to wild type animals. In addition, we show that aged
sphk-1 mutants were more susceptible to death due to poor heat stress response than aged wild type animals. This suggests that limiting sphingosine-1-phosphate production, specifically in aged animals, decreases their ability to survive exposure to stress. The putative ceramide kinase, T10B11.2, did not have life history trait phenotypes but did show locomotion phenotypes, suggesting it may be involved in neuronal function. Furthermore, we describe RNA sequencing experiments that examine gene expression changing during aging, specifically due to loss of
sphk-1. Finally, we describe ongoing experiments examining the roles of other sphingolipids in aging may help identify new signaling pathways that mediate healthspan.