The Division of Lung Diseases, National Heart, Lung, and Blood Institute (NHLBI), convened a workshop, "Intersection between Aging Biology and Pathobiology of Lung Diseases" on September 24 and 25, 2015. The workshop brought scientists in aging biology and lung biology together to examine the state of the art knowledge in aging biology and molecular pathobiology of lung diseases to identify the intersection between the two research areas, the knowledge gaps at the intersection, and exceptional opportunities in lung science that will (a) advance our mechanistic understanding of age-related lung disease and sleep perturbation, (b) elucidate the genetic and epigenetic factors that impact both aging and lung diseases, (c) develop/apply new technologies for/to lung research. The workshop also highlighted the potential to apply knowledge and technologies related to the lung biology of senescence to identify biomarkers and new therapeutic strategies for the diagnosis and treatment of lung diseases.
The presentations and discussions were clustered in five sessions:
1) Genetics, Epigenetics, and Systems Approaches.
2) Inflammation, Fibrosis and Lung Aging.
3) Adaptation to Stress.
4) Macrophages, T-Cells and Mesenchymal Cells in Aging.
5) Bioenergetics, Mitochondria and Aging.
The strong clinical association between advanced age and the incidence of acute and chronic lung disease suggests a fundamental link between the pathobiology of aging and many lung diseases. Hence, the study of aging biology needs to extend beyond aging researchers to encompass the overall community of researchers studying lung disease. Previous research has provided insight into the molecular mechanisms underlying aging at the cellular and organismal level, but additional research is needed to link these processes and pathways with phenotypes in the aging lung and with the susceptibility to lung disease. Key research challenges and opportunities that were identified by workshop participants are as follows.
- It is important to use aged animals for the study of lung disease; in some cases, findings in aged animals better recapitulate phenotypes of the human disease and aged models allow for interventions that selectively target aging and disease related processes.
- We need to better understand normal aging in the lung in human cohort studies: When does aging in the lung begin? Which cellular populations drive aging phenotypes? What are the lung-specific effects of interventions that extend lifespan and are being considered for therapies to prevent aging in healthy humans?
- How can we develop integrative systems-based platforms that can dynamically incorporate datasets that describe the genomics, transcriptomics, epigenomics, metabolomics and proteomics of the aging lung and generate interfaces through which investigators without a bioinformatics background can access the data to generate testable hypotheses?
- How do we reconcile the observations that common biologic hallmarks of aging are associated with remarkably diverse lung phenotypes, including COPD and pulmonary fibrosis, in different individuals? The growing importance of age-related lung diseases in limiting both lifespan and health span highlight the importance of understanding lung aging as part of an overall strategy to enhance health, lengthen life, and reduce illness and disability.
- Sznajder, Jacob I., M.D., Northwestern University
- Thannickal, Victor J., M.D., University of Alabama at Birmingham
- Amaral, Luis A. Ph.D., Northwestern University,
- Armanios, Mary, M.D., Johns Hopkins University
- Budinger, Scott, M.D., Northwestern University
- Busse, Paula, M.D., Icahn School of Med Mt. Sinai
- Chandel, Navdeep, Ph.D., Northwestern University
- Chen, Danica, Ph.D., University of California at Berkeley
- Finkel, Toren, M.D., Ph.D., National Heart, Lung, and Blood Institute
- Kelsey, Karl T., M.D., Brown University, Providence
- Kobor, Michael S., Ph.D., University of British Columbia
- Kovacs, Elizabeth, Ph.D., Loyola University
- Macian-Juan, Fernando, M.D., Ph.D., Albert Einstein College of Med, Bronx
- Mora, Ana, M.D., University of Pittsburgh
- Morimoto, Richard, Ph.D., Northwestern University
- Pardo, Annie, Ph.D.., Universidad Nacional Autónoma de México
- Rojas, Mauricio, M.D., University of Pittsburgh
- Selman, Moises, M.D., Instituto Nacional de Enfermedades
- Tuder, Rubin, M.D., University of Colorado
- Zhang, Xin, Ph.D., Pennsylvania State University
- Fuldner, Rebecca, Ph.D., National Institute of Aging
- Kiley, James P., Ph.D., National Heart, Lung, and Blood Institute
- Gan, Weiniu, Ph.D., National Heart, Lung, and Blood Institute
- MacGarvey, Nancy, M.D., National Heart, Lung, and Blood Institute
- Postow, Lisa, Ph.D., National Heart, Lung, and Blood Institute
- Sierra, Felipe, Ph.D., National Institute on Aging