{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:11Z","timestamp":1792790351696,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Genomics","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Mental Health","award":["K01MH128612"],"award-info":[{"award-number":["K01MH128612"]}]},{"name":"National Institute of Mental Health","award":["R01MH081873"],"award-info":[{"award-number":["R01MH081873"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01HD081199"],"award-info":[{"award-number":["R01HD081199"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Global aging measures did not differ between groups (all q &gt; .34). However, autistic adults had higher Brain (\u03b2 = 0.81), Blood (\u03b2 = 0.65), and Liver SystemsAge (\u03b2 = 0.58; all q &lt; .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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.12.751174","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:25:12Z","timestamp":1789773912000},"source":"Crossref","is-referenced-by-count":1,"title":["System-Specific Epigenetic Aging Signatures in Autistic Adults"],"prefix":"10.64898","author":[{"given":"Abigail","family":"Dickinson","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, University of California, Los Angeles"},{"name":"Center for Autism Research and Treatment, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace R.","family":"Lewis","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University"},{"name":"Department of Psychology, Arizona State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Geschwind","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, University of California, Los Angeles"},{"name":"Center for Autism Research and Treatment, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles"},{"name":"Department of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles"},{"name":"Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, University of California, Los Angeles"},{"name":"Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Lord","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, University of California, Los Angeles"},{"name":"Center for Autism Research and Treatment, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los 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