Oxidative Stress, Neuroinflammation, and Neuronal Vulnerability Begin in Midlife: a 7 Tesla Magnetic Resonance Spectroscopy Healthy Adult Lifespan Study

ABSTRACT INTRODUCTION While changes associated with age-related diseases, like oxidative stress, begin in midlife, most aging studies focused on older individuals. Our study assessed in vivo brain metabolites in healthy adults, including the understudied middle-age group. METHODS 7 tesla magnetic resonance spectroscopy data were acquired from 95 healthy adults (48 women) aged 20-79 years. Eight metabolites were measured in posterior cingulate cortex (PCC) and centrum semiovale white matter (CSWM). RESULTS With increasing age, we found (a) lower glutathione and glutamate, and higher myo- inositol in PCC, and (b) lower N -acetylaspartate and glutamate, and higher myo -inositol, total creatine, and N -acetylaspartyl-glutamate in CSWM. Notably, most changes started in midlife and were driven by age-related changes in women. DISCUSSION Overall, we found evidence that oxidative stress, neuroinflammation, and neuronal vulnerability begin in midlife in healthy adults. Targeting these processes in midlife may slow brain aging and reduce age-related neurodegenerative diseases risk, including Alzheimer’s disease. GRAPHICAL ABSTRACT