In fact, mitochondrial DNA deletions and point mutations accumulate during normal CNS aging and, together with increased production of reactive oxygen species, are thought to be responsible for age-related neuroaxonal degeneration. As our sample age range starts at 23 years, we have not been able to ascertain whether age-related changes in the spinal cord occur before the early twenties. Similarly, it is possible that subjects older than 65 could show accelerated decline of tNAA. However, within our sample age range of 23265, we did not find a quadratic association between age and the concentrations of tNAA and Glx. Future longitudinal studies will study the decline trajectory of tNAA within individuals by following them up for a decade or longer. Interestingly, in healthy brain aging, reductions in tNAA have been widely reported in grey matter regions, but rarely seen in the white matter which may, in part, be explained by a slower rate of aging-related white matter volume loss in the brain when compared with grey matter. In a previous brain MRS study, a different temporal behaviour of NAA/tCho has been observed between the white matter and grey matter. In the cerebral white matter, the NAA/tCho ratio increases rapidly during the first decade of life before peaking in the second or early third decade, followed by a steady decline starting in the latter half of the third decade of life, whilst in the grey matter, the NAA/tCho ratio enters a steady decline from childhood. Although we have not been able to assess if the age-related decline in tNAA in the spinal cord is also tissue dependent in the current study, due to the difficulty in segmenting white matter and grey matter tissues within the spinal cord, it is possible that tNAA concentration declines faster in spinal grey matter than white matter with age and this could be an area for future research. Glutamate, the major excitatory neurotransmitter in mammals plays a major role in the coordination of basic propulsive movement synergy for locomotion at the spinal level and processing and transmitting sensory information in the spinal cord. Glu, as opposed to Glx, which represents a sum of Glu and glutamine, is difficult to measure in the spinal cord. We found that Glx concentration was negatively associated with age. Between 75–86% of the Glx signal is thought to come from Glu, and this decline in spinal Glx could largely be explained by neuroaxonal degeneration. As Glu is largely present in neurones at synaptic terminals, with Glu from the extracellular compartment and glial cells SCH772984 considered to be present in very low concentration and therefore contribute very little to the spectroscopy signal, it would be expected that Glu will decrease where there is neuronal loss. However, it is interesting that the rate of decline in Glx concentration with age is more rapid than tNAA, which might suggest that the reduction in glutamateglutamine neurotransmitter pool are driven by more than neuronal loss alone.