Oxidative Stress, Neuroinflammation, and Neuronal Loss Start in Midlife: a 7 Tesla Magnetic Resonance Spectroscopy Healthy Adult Age-Span Study

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: 7T magnetic resonance spectroscopy data were acquired from 87 healthy adults (45 women) aged 20-79 years. Levels of 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 N-acetylaspartyl glutamate, myo-inositol, and total creatine in CSWM. Notably, these changes started in midlife and were largely driven by age-related changes in women. DISCUSSION: Overall, we found evidence that (a) oxidative stress, (b) neuroinflammation, and (c) neuronal loss begin in midlife of healthy adults. Targeting these mechanisms in midlife may slow brain aging and reduce the risks of developing age-related diseases.