Aging and anatomical variations in lung tissue stiffness

Abstract

Lung function is inherently mechanical in nature and depends on the capacity to conduct air and blood to and from the gas exchange regions. Variations in the elastic properties of the human lung across anatomical compartments and with aging are likely important determinants of lung function but remain relatively poorly characterized. Here we applied atomic force microscopy microindentation to characterize human lung tissue from subjects ranging in age from 11 to 60 yr old. We observed striking anatomical variations in elastic modulus, with the airways (200- to 350-µm diameter) the stiffest and the parenchymal regions the most compliant. Vessels (diameter < 100 µm) represented an intermediate mechanical environment and displayed diameter-dependent trends in elastic modulus. Binning our samples into younger (11-30 yr old) and older (41-60 yr old) groups, we observed significant age-related increases in stiffness in parenchymal and vessel compartments, with the most pronounced changes in the vessels. To investigate cellular mechanisms that might contribute to vascular stiffening with aging, we studied primary human pulmonary artery smooth muscle cells from subjects ranging in age from 11 to 60 yr old. While we observed no change in the mechanical properties of the cells themselves, we did observe trends toward increases in traction forces and extracellular matrix deposition with aging. These results demonstrate age-related changes in tissue mechanical properties that likely contribute to impaired lung function with aging and underscore the potential to identify mechanisms that contribute to mechanical tissue remodeling through the study of human cells and tissues from across the aging spectrum.

Cross-platform mechanical characterization of lung tissue

“…Higher variability from cavitation compared to indentation and SAOS may have been due to fact that bronchiole-free areas were selected in the excised tissues for indentation and SAOS ( S1 Fig ). Sicard et al very recently performed AFM on human lung tissue, reporting a modulus of 1.87 ± 0.95 kPa for parenchyma, and 7.17 ± 4.03 kPa for pulmonary vessels [ 30 ]. This result is interesting in the context of our study, where we took measurements only on parenchymal tissue, and saw 1.9±0.5 kPa with micro-indentation and 6.1±1.6 kPa with cavitation.…”

TRPV4—A Missing Link Between Mechanosensation and Immunity

“…Finally, substrate stiffness is regulated by the composition of the ECM which changes as a function of physiological (development, aging) and pathophysiological (atherosclerosis, hypertension, fibrosis) processes (90)(91)(92)(93). TRPV4 has been identified as a major mechanosensor for substrate stiffness, but so far this function has been exclusively attributed to parenchymal cells (30,31,(94)(95)(96)).…”

An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

“…The ECM of old lungs features changes in tensile strength and elasticity, which were discussed to be a possible consequence of fibroblast senescence 8 . Using atomic force microscopy, age-related increases in stiffness of parenchymal and vessel compartments were demonstrated recently 9 , however, the causal molecular changes underlying these effects are unknown.…”