515-P: Do Circulating Sphingolipid Species Correlate with Age? A Study in a Normoglycemic Population

Objective: Sphingolipids (SPL) in circulation have been associated with pathological outcomes of metabolic and cardiovascular diseases that are known to be influenced by aging. We sought to determine the age association of plasma SPL species in people with no diabetes. Methods: We determined plasma levels (pmole/mL) of 58 SPL species, including ceramides (Cer), monohexosylceramides (MHC), sphingomyelins (SM), sphingosine (So), and sphingosine 1-phosphate (S1P) in 239 normoglycemic participants using LC-MS/MS after dividing them into five age groups, 19-29y (n=46), 30-39y (n=47), 40-49y (n=64), 50-59y (n=67), and ≥60y (n=15). Correlation analysis identified SPL species that differ significantly among the age groups and that significantly correlate with aging. Results: We identified the ratio of C18:0/C18:1 in Cer, MHC, and SM differed significantly in different age groups along with some very-long-chain (VLC) species of MHC and SM, SM C14:0, total SM, and SM% of SPL, which remained significant after adjusting for gender, race, BMI, waist circumference, FPG, and 2hPG. Interestingly, Cer C18:1 (r=0.20, p0.01) positively correlated with aging, and the ratio of Cer C18:0/C18:1 (r= -0.27, p0.0001) and MHC (r= -0.23, p0.001) correlated negatively. While levels of So (r= -0.29, p0.0001) and MHC C26:0 (r= -0.20, p0.01), MHC C28:0 (r= -0.25, p0.0001), MHC C34:0 (r= -0.23, p0.001) and MHC ratio of C26:0/C26:1 (r= -0.27, p0.0001) and MHC% of SPL (r= -0.20, p0.01) correlated negatively, SM% of SPL (r=0.21, p0.001) correlated positively. Conclusions: Our results show that the plasma concentration of certain SPL species and ratios differ with age and correlate differentially with age. Thus, alterations in SPL metabolism may be linked to aging and age-related disorders. Disclosure N. Feto: None. P. Asuzu: None. F.B. Stentz: None. J.Y. Wan: None. S. Dagogo-Jack: Consultant; Merck Sharp Aerami. N. Mandal: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK128129, R01 DK067269, and DK 48411)