Brain aging in neurodevelopmental disorders: a narrative review of oxidative, inflammatory, and mitochondrial mechanisms.

Abstract

Neurodevelopmental disorders (NDDs), including autism spectrum disorder, attention deficit/hyperactivity disorder, intellectual disability, and Down syndrome, are increasingly examined through the lens of aging. Emerging evidence indicates that individuals with NDDs may exhibit accelerated or atypical brain aging, characterized by cognitive decline and increased vulnerability to neurodegenerative conditions such as Alzheimer's and Parkinson's disease. This narrative review synthesizes current findings on biological mechanisms implicated in altered aging trajectories, with emphasis on oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and cellular senescence. These processes, detectable from early development, mirror pathways involved in neurodegeneration, suggesting shared molecular cascades that increase susceptibility to early aging. Biomarker studies report telomere shortening, elevated plasma glial fibrillary acidic protein and neurofilament light chain levels, and deviations in neuroimaging-derived brain age, supporting the hypothesis of altered biological aging in NDDs. However, the limited number of longitudinal lifespan studies, along with marked heterogeneity in etiology, clinical profiles, and comorbidities, constrains causal inference. Psychosocial and environmental factors, including chronic stress, social exclusion, medical comorbidities, and lifestyle influences, further shape aging outcomes. Integrating biological, behavioral, and environmental markers is essential to advance monitoring and inform early interventions aimed at promoting healthier cognitive and functional aging in neurodivergent populations.