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bioRxiv · 10.64898/2026.09.12.751174

System-Specific Epigenetic Aging Signatures in Autistic Adults

Dickinson, A.·Lewis, C. R.·Geschwind, D. H.·Carroll, J. E.·Lord, C.
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Abstract

Background: Autism is a lifelong neurodevelopmental condition, but the biological processes shaping aging are poorly understood. DNA methylation-based measures index physiological decline and mortality risk independently of chronological age. We tested whether biological aging differs in autistic adults, whether differences are system-specific, and which factors predict within-autism variation. Methods: Saliva DNA methylation (Illumina EPIC) was assayed in 37 autistic adults (31 male, 6 female; mean age 29.8 years), followed from early childhood, spanning a broad ability range including intellectual disability, and 188 non-autistic adults from four public datasets, processed jointly. Fifteen measures were calculated: four global (Horvath, GrimAge, DunedinPACE, SystemsAge) and 11 system-specific SystemsAge subscores. Models adjusted for age, sex, and epithelial-cell proportion. Results: Global aging measures did not differ between groups (all q > .34). However, autistic adults had higher Brain ({beta} = 0.81), Blood ({beta} = 0.65), and Liver SystemsAge ({beta} = 0.58; all q < .01), with Brain and Blood robust across sensitivity analyses. Within autism, aging measures were unrelated to symptom severity, IQ, co-occurring diagnoses, or medication use. Instead, elevations were associated with psychosocial circumstances, including a lack of structured daytime activity, greater loneliness, and lower quality of life. Conclusions: Differences in aging biology in autism appeared system-specific rather than global, with no evidence of generalized epigenetic age acceleration. This vulnerability appeared more closely tied to psychosocial factors than core clinical features. System-specific DNAm measures may therefore provide a more sensitive framework for identifying biological heterogeneity and potentially modifiable contributors to healthy aging in autistic adulthood.

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Dickinson, A., Lewis, C. R., Geschwind, D. H., Carroll, J. E., Lord, C.. 2026-09-18. System-Specific Epigenetic Aging Signatures in Autistic Adults. https://doi.org/10.64898/2026.09.12.751174

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