Longitudinal associations between blood lysophosphatidylcholines and skeletal muscle mitochondrial function

Abstract

Lysophosphatidylcholines (LPCs) are phospholipids critical in the synthesis of cardiolipin, an essential component of mitochondrial membranes. Lower plasma LPCs have been cross-sectionally associated with lower skeletal muscle mitochondrial function, but whether lower LPCs and their decline over time are longitudinally associated with an accelerated decline of mitochondria function is unknown. We analyzed data from 184 participants in the Baltimore Longitudinal Study of Aging (mean age: 74.5 years, 57% women, 25% black) who had repeated measures of plasma LPCs (16:0, 16:1, 17:0, 18:0, 18:1, 18:2, 20:3, 20:4, 24:0, and 28:1) by liquid chromatography-tandem mass spectrometry and repeated measures of skeletal muscle oxidative capacity (kPCr) assessed by 31P magnetic resonance spectroscopy over an average of 2.4 years. Rates of change in kPCr and each LPC were first estimated using simple linear regression. In multivariable linear regression models adjusted for baseline demographics and PCr % depletion, lower baseline LPC 16:1 and faster rates of decline in LPC 16:1 and 18:1 were significantly associated with a faster rate of decline in kPCr (B = − 0.169, 95% CI: − 0.328, − 0.010, p = 0.038; B = 0.209, 95% CI: 0.065, 0.352, p = 0.005; B = 0.156, 95% CI: 0.011, 0.301, p = 0.035, respectively). Rates of change in other LPCs were not significantly associated with change in kPCr (all p > 0.05). Lower baseline concentrations and faster decline in selected plasma lysophosphatidylcholines over time are associated with faster decline in skeletal muscle mitochondrial function. Strategies to prevent the decline of plasma LPCs at an early stage may slow down mitochondrial function decline and impairment during aging.