Characterizing Biological Aging for Heart and Lung Diseases Using Multi-omics Ageotypes

About This Grant

PROJECT SUMMARY/ABSTRACT As the aging population continues to grow worldwide, age-related chronic heart and lung diseases have become an increasingly serious public health issue. Consequently, understanding the relationships between aging and these diseases is crucial for effective prevention and treatment strategies. However, the complexity of the aging process, which involves cellular senescence, inflammatory responses, and oxidative stress, and its differential impact on individuals, makes it difficult to identify the relationship between specific aging processes and the development of various heart and lung diseases. The recent concept of "ageotypes," which clusters individuals into similar molecular profiles throughout the aging process, offers a framework to identify molecular mechanisms of aging and connect this with chronic heart and lung diseases. However, existing studies of ageotypes have been limited by small sample sizes, short follow-up periods, and insufficient omics data, limiting their overall utility. This proposal aims to generate multi-omic ageotypes to understand the molecular mechanisms of aging that lead to chronic heart and lung diseases. The overall objectives of this proposal are to: 1) develop and validate multi-omic ageotypes using metabolomics and epigenetics data in two large cohorts with electronic medical records (EMR) data; 2) identify the molecular drivers that significantly contribute to each ageotype, particularly in relation to heart and lung diseases; 3) elucidate the relationship between ageotypes and chronic heart and lung diseases. Through personalized approaches for different ageotypes, we may not only improve the treatment of chronic heart and lung diseases but also potentially delay or prevent their onset, thereby having a profound impact on public health. Dr. Yulu Chen is a bioinformatician specializing in using multi-omic approaches to study complex disease phenotypes, particularly respiratory diseases and aging. Her overarching career goal is to become an independent researcher with the skills to enhance the biological understanding and clinical management of aging and related heart and lung diseases through integrative omics techniques. Dr. Chen's strong quantitative and methodological background, combined with the support from a diverse and world-class mentoring and advisory team from the Channing Division of Network Medicine at Brigham and Women’s Hospital and Harvard Medical School, has well-prepared her for the proposed research. The proposed career development plan builds on her previous training and outlines five training objectives to enhance her trajectory toward becoming an independent researcher: 1) expand her skills in integrative omics techniques, particularly network-based approaches for integrating multi-omic datasets; 2) enhance her knowledge and application of epigenomic data; 3) gain a deeper understanding of the phenotypes and experimental measurements of heart and lung diseases; 4) broaden her understanding of the biological mechanisms of aging; 5) improve her skills in research design, mentorship, scientific ethics, and research communication.