The effects of both age and sex on irisin levels in paired plasma and cerebrospinal fluid in healthy humans

Background: Adipo-myokine irisin has important effects on the metabolism and functioning of multiple tissues and organs. However, the effects of aging and sex on irisin levels in cerebrospinal fluid (CSF) and on circulation have not been comprehensively studied. Objective: To investigate whether aging and sex can affect irisin levels in both CSF and plasma; to determine whether CSF irisin uptake involves a saturable transport mechanism. Design and methods: In the present study, the irisin levels in paired CSF and plasma samples drawn from 71 healthy individuals were used to investigate effects by using commercial ELISA kits and mass spectrometry. Results: Multiple linear regression analysis results showed that CSF irisin levels are positively correlated with the CSF/plasma irisin ratio and age and that these levels present a reverse correlation with BMI. Age-related increases in CSF levels are validated by using ELISA and mass spectrometry. Higher plasma irisin levels are observed in men than women. CSF and plasma irisin levels are nonlinearly associated with the CSF/plasma irisin ratio, BMI, age and F scores. The CSF/plasma irisin ratio is U-shaped and associated with age. Conclusions: There might be an age-related increase in irisin levels in the cerebrospinal fluid of healthy humans. Circulating irisin levels are higher in males than in females in the healthy population. A saturable mechanism might be involved in mediating the transport of circulating irisin across the blood-brain barrier. Factors shaping irisin levels for both circulation and the CSF of healthy humans must be further defined in future experiments.