Abstract
Autism spectrum disorder (ASD) is characterized by impaired social communication and behavioral problems. An increased risk of premature mortality has been observed in individuals with ASD. Therefore, we hypothesized that biological aging is accelerated in individuals with ASD. Recently, several studies have established genome-wide DNA methylation (DNAm) profiles as 'epigenetic clocks' that can estimate biological aging. In addition, ASD has been associated with differential DNAm patterns. We used two independent datasets from blood samples consisting of adult patients with high-functioning ASD and controls: the 1st cohort (38 ASD cases and 31 controls) and the 2nd cohort (6 ASD cases and 10 controls). We explored well-studied epigenetic clocks such as HorvathAge, HannumAge, SkinBloodAge, PhenoAge, GrimAge, and DNAm-based telomere length (DNAmTL). In addition, we investigated seven DNAm-based age-related plasma proteins, including plasminogen activator inhibitor-1 (PAI-1), and smoking status, which are the components of GrimAge. Compared to controls, individuals with ASD in the 1st cohort, but not in the 2nd cohort, exhibited a trend for increased GrimAge acceleration and a significant increase of PAI-1 levels. A meta-analysis showed significantly increased PAI-1 levels in individuals with ASD compared to controls. Our findings suggest there is no epigenetic age acceleration in the blood of individuals with ASD. However, this study provides novel evidence regarding increased plasma PAI-1 levels in individuals with high-functioning ASD. These findings suggest PAI-1 may be a biomarker for high-functioning ASD, however, larger studies based on epigenetic clocks and PAI-1 will be necessary to confirm these findings.
Highlights
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impaired social communication and behavioral problems that affects about 1% of the worldwide population [1]
A meta-analysis showed significantly increased plasminogen activator inhibitor-1 (PAI-1) levels in individuals with ASD compared to controls
This study provides novel evidence regarding increased plasma PAI-1 levels in individuals with high-functioning ASD. These findings suggest PAI-1 may be a biomarker for high-functioning ASD, larger studies based on epigenetic clocks and PAI-1 will be necessary to confirm these findings
Summary
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impaired social communication and behavioral problems that affects about 1% of the worldwide population [1]. An increased risk of premature mortality has been observed in individuals with ASD, which results from both natural causes and suicide [4,5,6]. Even after adjusting for comorbid psychiatric disorders such as intellectual disability, the mortality risk in individuals with ASD is elevated for natural causes but not for suicide [5]. As a putative explanation for these observations, we propose a hypothesis that ASD is associated with accelerated biological aging. Autism spectrum disorder (ASD) is characterized by impaired social communication and behavioral problems. An increased risk of premature mortality has been observed in individuals with ASD. ASD has been associated with differential DNAm patterns.
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