Understanding and preventing aging of the human heart

Diseases of the heart muscle and valves remain leading causes of death and disability globally, but their etiological spectrum has changed over time towards predominance of aging-related conditions.My translational research program combines methods in epidemiology, molecular biology, and clinical research to (a) identify molecular determinants and mechanisms for cardiac aging and aging-related heart disease (b) evaluate the value of identified biomarkers for early disease detection and preventive strategies in a clinical setting.Workplan: (1) determine life-course trajectories for individual conditions and disease stages using aggregated nation-wide registers (2) identify molecular determinants of aging-related heart disease by application of multi-omic tools to large cohorts and international consortia including genome-wide studies of >150 000 cases and 2 million controls (3) identify molecular signatures of aging and disease in a large cohort of human hearts by multi-omic profiling and assess causality using mendelian randomization (4) evaluate clinical utility of biomarkers in prospective studies and clinical effects in a randomized trial of a compound that promotes proteostasis and mitochondrial respiration in vivo.This research program is expected to provide new insights into cardiac aging and disease pathophysiology, identification of therapeutic targets and clinical biomarkers, and information about human effects and clinical value of targeting such biomarkers.