System-Specific Epigenetic Aging Signatures in Autistic Adults.

Authors

Abigail Dickinson, Candace R Lewis, Daniel H Geschwind, Judith E Carroll, Catherine Lord

Published in

bioRxiv : the preprint server for biology. Sep 18, 2026. Epub Sep 18, 2026.

Abstract

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.
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.
Global aging measures did not differ between groups (all q > .34). However, autistic adults had higher Brain (β = 0.81), Blood (β = 0.65), and Liver SystemsAge (β = 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.
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.

PMID:
42779660
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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