Toward Healthy Aging in Adults with Autism: A Longitudinal Clinical and Multimodal Brain Imaging Study - PROJECT SUMMARY/ABSTRACT Autism spectrum disorder (ASD) is a lifelong disorder that has consequences throughout adulthood. Recent population health studies indicate that aging autistic adults have shorter life expectancy and increased rates of physical and mental health problems. However, there is a paucity of studies that have focused on the progression of health and wellness with aging in ASD and factors that can contribute to better or worse outcomes. In this Autism Center of Excellence (ACE) Network project, the Interdisciplinary Science to Learn about Autism – Aging (ISLA-A) Network will deploy a harmonized, optimized, and innovative protocol to investigate the effects of aging in autism in one of the largest prospective longitudinal cohort studies of autistic adults to date. The aims of the ISLA-A center are 1) to establish and follow a large cohort of autistic male and female adults, siblings and age- and sex- matched non-autistic adults with a comprehensive harmonized research protocol to investigate multi- modal aspects of aging, including measures of clinical severity, physical and mental health, cognitive aging, brain structure and function, and epigenetic measures of biological aging; 2) to characterize both group and individual age-related changes in autism severity, health, wellness and brain measures with aging; 3) to investigate the relationships between clinical, health, and brain imaging measures; and 4) to investigate whether biological aging is accelerated in autism using new epigenetic measures of aging. The overarching goal of the ISLA-A Network is to create a comprehensive, harmonized, and high-dimensional dataset that will characterize trajectories of aging in autism that may be used to investigate whether early or accelerated aging is a hallmark feature of autism, and how aging in autism influences health and brain outcomes. The inclusion of siblings, who share genetics with the autistic adult cohort, will help to identify autism-specific factors related to aging and outcomes. The ISLA-A study results will identify candidate factors that are predictive to autism aging outcomes and will guide the development of interventions and services to improve outcomes. This new large, multi-modal, longitudinal, and generalizable dataset will be shared with the autism research community for independent studies. Overall, the ISLA-A Network study will generate a rich, high-impact resource for better understanding of aging in autism, with the ultimate goal of improving the health and support of autistic adults.