Blue journal conference. Aging and susceptibility to lung disease

Abstract

The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease.

Figure 1.

Lung disease is more common in the elderly. Estimates of annual U.S. death rates for chronic obstructive pulmonary disease (COPD) and pneumonia and the estimated annual incidence rate for idiopathic pulmonary fibrosis (IPF) are shown. Data from References , , and .

Figure 2.

Understanding aging hallmarks at the molecular level. Environmental factors including infections, environmental toxins, and dietary risk factors can act through signaling pathways to directly alter the structure and function of cellular proteins or can affect the proteome indirectly by damaging genomic DNA or modulating gene transcription. In addition, signaling pathways activated in response to environmental stress alter metabolism, which supplies energy and biosynthetic intermediates for genome maintenance, gene transcription, and proteostasis. Some of the hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, changes in noncoding RNAs including microRNAs and alterations in proteostasis) are known to act primarily at the level of DNA, RNA, or protein; however, their integrated effects on the genome, transcriptome, proteome, and metabolome are not known. A similar approach combining fundamental mechanistic biology with systems-based strategies is needed to understand how aging hallmarks including cellular senescence, stem cell dysregulation, immune dysregulation and extracellular matrix dysfunction contribute to the development of age-related lung disease. COPD = chronic obstructive pulmonary disease; miRNA = micro-RNA; MODS = multiple organ dysfunction syndrome.