In recent decades, Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), has become the most common chronic liver condition, leading to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. This trend isn't confined to adults; children and adolescents are also affected, increasing the need for liver transplants among young adults. Two decades ago, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established the Non- Alcoholic Steatohepatitis Clinical Research Network (NASH CRN) to advance clinical and translational research in adult and pediatric MASLD. Their mission is to translate scientific findings from lab, clinical, and population studies into practical applications, ultimately reducing MASLD incidence, slowing disease progression, and improving clinical outcomes. Over 20 years, NASH CRN has led NAFLD research, creating valuable databases, conducting randomized trials, and disseminating high-quality studies. Looking ahead, the CRN will leverage its established infrastructure and accumulated knowledge to develop diagnostic tests, biomarkers for disease progression, and safe, cost-effective NASH treatments. This renewal application aims to complete ongoing NASH CRN studies: Database 3 (DB3) and Vitamin E Dosing Study (VEDS). Furthermore, the Duke/Lurie Children's Memorial site proposes novel investigations focusing on accelerated senescence to predict high-risk populations in pediatric and adult cohorts. The central hypothesis is that patients prone to premature hepatocyte senescence are at greater risk of progressive liver degeneration, severe hepatic fibrosis, and higher morbidity and mortality due to MASLD. These investigations draw from recent research, utilizing existing data and biosamples while considering biological disparities to improve outcomes in pediatric and adult populations. The goal is to deepen our understanding of MASLD and pioneer innovative approaches for better disease management.