A Pilot Study of Age-Related Changes in the Sphingolipid Composition of the Rat Sarcoplasmic Reticulum

Background: Muscle strength declines more rapidly than muscle size, manifesting as a loss of muscle quality. One putative contributor to this impairment of muscle quality is impaired sarcoplasmic reticulum (SR) function.

Objectives: The principal objective of this study was to characterize the sphingolipid composition of the SR in adult and aging rat muscles. A secondary, exploratory objective was to test for associations between SR sphingolipids and SR function (i.e., Ca2+ release).

Design: Using an animal model, the objectives were evaluated in a pre-clinical, cross-sectional study.

Setting: Data were collected in an academic research laboratory.

Participants: Medial gastrocnemius muscles of adult (n=8; 7-8 months) and aged (n=8; 24-25 months), male F344/BN hybrid rats were processed to extract SR.

Measurements: Sphingolipids in the SR were measured using tandem mass spectrometry. Fatty acid concentrations within the major sphingolipid classes were evaluated via Principal Component Analysis (PCA). In a subset of samples, SR Ca2+ release rates were determined using fluorometric methods, and associations with specific (based on results of PCA) fatty acid concentrations were evaluated.

Results: Aging SR showed an overall decline in the ratio of unsaturated to saturated fatty acids. Age-specific differences were observed for hexosylceramide and ceramide-1-phosphate. Within subset of samples with SR Ca2+ release data, a significant negative association between Ca2+ release and C1P18:0 and trends for positive associations with hexCER24:0 and 24:1 were observed.

Conclusions: These preliminary, pre-clinical data suggest that changes in SR sphingolipids may play a role in age-related impairment of muscle function. Further work is needed to explore this hypothesis, as SR sphingolipids may prove a fruitful target for interventions, be they physical (i.e., exercise), nutritional or pharmacological.