Magnetic resonance spectroscopy as a non-invasive tool for assessing brain and muscle adaptation to exercise training in older age: a scoping review into existing research

Background: Exercise training has attracted increasing attention as a non-pharmacological intervention approach to counteract age-related deterioration of brain and muscle function, yet objective biomarkers are needed to understand mechanisms and optimize interventions. Magnetic resonance spectroscopy (MRS) provides noninvasive, in vivo assessment of metabolic profiles altered by aging and exercise. However, MRS-based exercise research in older populations remains limited. This scoping review aims to identify brain and muscle metabolites detectable by MRS that can serve as markers of exercise training effects in aging. Methods: We conducted a literature search from inception to October 2024 in PubMed, Embase, Web of Science, and Scopus. Inclusion criteria comprised randomized control trials (RCT) and observational studies including older adults (>= 60 years) who underwent exercise training interventions which were preceded/followed by brain/muscle MRS scanning. Results: Fourteen studies were included. Exercise intervention characteristics varied from low or moderate aerobic type of exercise to high intensity training, with the interventions placing variable emphasis on the strength-endurance continuum. Scanning methods were 1H brain MRS (n = 6), 31P brain MRS (n = 1), 31P muscle MRS (n= 8) and 1H muscle MRS (n = 1). Main 1H-MRS brain neurometabolic outcomes were the ratios to creatine of total N-acetyl-aspartate (tNAA/tCr) and total choline (tCho/tCr) in the right/left hippocampus. However, findings regarding the effect of exercise training interventions on these neurometabolic outcomes were inconclusive. 31P muscle MRS demonstrated an increase in phosphocreatine (PCr) recovery rate from pre-to-post exercise suggesting an improvement of mitochondrial function following exercise when applying exercise interventions with an emphasis on improving cardiometabolic functions. Conclusions: Despite limited guidance on methods and biomarkers, this scoping review supports MRS as a promising tool for monitoring exercise-induced metabolic changes in muscle and brain of older adults. However, standardized methodologies and larger number of studies are required to determine which metabolites reliably reflect exercise benefits in aging brain and muscle.