The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop

Abstract

Death from chronic lung disease is increasing and chronic obstructive pulmonary disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization, and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as life span. This review summarizes the findings of a joint workshop sponsored by the NIA and NHLBI that brought together investigators focused on aging and lung biology. These investigators encouraged the use of genetic systems and aged animals in the study of lung disease and the development of integrative systems-based platforms that can dynamically incorporate data sets that describe the genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging lung in health and disease. Further research was recommended to integrate benchmark biological hallmarks of aging in the lung with the pathobiology of acute and chronic lung diseases with divergent pathologies for which advanced age is the most important risk factor.

Keywords: Age-related pathology; Biology of aging; Lungs/pulmonary.

Figure 1.

Models for the age-related decline in lung health. Red lines represent age-related changes in lung health, blue lines the effect of potential therapies to preserve lung health during aging. A. Progressive decline. According to this model, the rate of accumulation of age-related damage to the lung over time determines whether, and at what age, an individual will develop respiratory disability (dashed line). Effective interventions should slow the rate of age-related decline in lung funciton to preserve lung health over the life span (blue arrow). B. Loss of resilience. Even in individuals who maintain their lung function over time, injury induced by environmental challenges (infections, inhaled toxins, etc) over the life span might be followed by incomplete resolution, resulting in intermittent step-declines in lung health. Interventions to improve lung resilience could reduce the severity of lung damage in response to a given environmental challenge or improve lung regeneration after injury (blue arrows). C. Impaired lung development. Data from recent longitudinal studies of lung function suggest that some individuals fail to achieve normal lung function during early adulthood. These individuals might be particularly prone to the age-related decline in lung health. Interentions that minimize antenatal and postnatal exposures to environmental factors that impair lung development is predicted to preserve lung health during aging in these individuals (blue arrow). D. Combined age-related progressive lung dysfunction and loss of lung resilience, particularly in patients with impaired lung development, can dramatically reduce the age at which respiratory disability develops.