![]() Aging decreases ciliary beat frequency in mice, thereby decreasing mucociliary clearance and partially explaining the predisposition of the elderly to pneumonia 5. Advanced age causes a progressive impairment of lung function even in otherwise healthy individuals, featuring structural and immunological alterations that affect gas exchange and susceptibility to disease 4. These protection mechanisms seem to deteriorate with advanced age, since aging is the main risk factor for developing chronic lung diseases, including chronic obstructive pulmonary disease (COPD), lung cancer, and interstitial lung disease 2, 3. ![]() A range of protection mechanisms are in place, including a highly specialized set of lung-resident innate and adaptive immune cells that fight off infection, as well as several stem and progenitor cell populations that provide the lung with a remarkable regenerative capacity upon injury 1. As the organ with the largest surface area (~70 m 2 in humans), the lung is constantly exposed to a plethora of environmental insults. The intricate structure of the lung enables gas exchange between inhaled air and circulating blood. Computational integration of the aging proteome with the single cell transcriptomes predicts the cellular source of regulated proteins and creates an unbiased reference map of the aging lung. Proteomic profiling reveals extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and collagen XIV. We observe cell type-specific effects of aging, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts and altered relative frequency of airway epithelial cells as hallmarks of lung aging. We show that aging leads to increased transcriptional noise, indicating deregulated epigenetic control. Here, we use single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity states across 30 cell types and chart the lung proteome of young and old mice. ![]() Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. ![]()
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