ABSTRACT
BACKGROUND: During biological aging, significant metabolic dysregulation in the central nervous system may lead to cognitive decline and neurodegeneration. However, the metabolomics of the aging process in cerebrospinal fluid (CSF) has not been thoroughly explored. METHODS: In this cohort study of CSF metabolomics using liquid chromatography-mass spectrometry (LC-MS), fasting CSF samples collected from 92 cognitively unimpaired adults aged 20-87 years without obesity or diabetes were analyzed. RESULTS: We identified 37 metabolites in these CSF samples with significant positive correlations with aging, including cysteine, pantothenic acid, 5-hydroxyindoleacetic acid (5-HIAA), aspartic acid, and glutamate; and two metabolites with negative correlations, asparagine and glycerophosphocholine. The combined alterations of asparagine, cysteine, glycerophosphocholine, pantothenic acid, sucrose, and 5-HIAA showed a superior correlation with aging (AUC = 0.982). These age-correlated changes in CSF metabolites might reflect blood-brain barrier breakdown, neuroinflammation, and mitochondrial dysfunction in the aging brain. We also found sex differences in CSF metabolites with higher levels of taurine and 5-HIAA in women using propensity-matched comparison. CONCLUSIONS: Our LC-MS metabolomics of the aging process in a Taiwanese population revealed several significantly altered CSF metabolites during aging and between the sexes. These metabolic alterations in CSF might provide clues for healthy brain aging and deserve further exploration.
Subject(s)
Aging , Chromatography, Liquid , Cysteine , Metabolome , Tandem Mass Spectrometry , Female , Humans , Male , Aging/cerebrospinal fluid , Aging/metabolism , Asparagine/cerebrospinal fluid , Chromatography, Liquid/methods , Cohort Studies , Cysteine/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Pantothenic Acid/cerebrospinal fluid , Tandem Mass Spectrometry/methods , Healthy Volunteers , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Cognition/physiology , Fasting/cerebrospinal fluid , Fasting/metabolismABSTRACT
Although the biochemical roles of most vitamins in the body are reasonably well understood, our knowledge of how the body transports and metabolizes the vitamins is incomplete. This paper summarizes the information available on riboflavin, vitamin B-6, biotin, vitamin D, vitamin C, and pantothenic acid. As might be expected on the basis of the diverse chemistry and biology of these substrates, the body has quite unique mechanisms for handling each of them.
Subject(s)
Vitamins/metabolism , Animals , Ascorbic Acid/metabolism , Biological Transport , Biotin/metabolism , Brain/metabolism , Carrier Proteins/metabolism , Humans , In Vitro Techniques , Intestinal Absorption , Kidney/metabolism , Kinetics , Liver/metabolism , Pantothenic Acid/cerebrospinal fluid , Pantothenic Acid/metabolism , Protein Binding , Pyridoxine/metabolism , Rats , Receptors, Calcitriol , Receptors, Steroid/metabolism , Riboflavin/metabolism , Vitamin D/blood , Vitamin D/metabolism , Vitamins/bloodABSTRACT
Calcium-hopantenate (HOPA), a derivative of GABA, was administered to 9 psychiatric patients with neuroleptics-induced tardive dyskinesia. In a clinical study, involuntary movements have improved significantly after a 4-8-week medication. Although there was no correlation between the cerebrospinal fluid (CSF) levels of HOPA, GABA, HVA or clinical response, the CSF HOPA levels significantly correlated with changes in the CSF GABA levels. These results suggest that HOPA alleviates the symptoms of tardive dyskinesia being mediated by the central GABAergic mechanisms.
