The Aging Microenvironment Drives Alveolar Macrophage Changes in Aging [Bisulfite-Seq]

Our study shows that the aging lung microenvironment shapes the transcriptional phenotype of alveolar macrophages during aging. Except during acute injury when alveolar macrophage differentiation is incomplete, cellular ontogeny makes little difference in determining the transcriptional response of alveolar macrophages. Studies with parabiosis suggest the age-related changes in the alveolar microenvironment occur independently of circulating factors or cells. Our findings suggest that changes that target the microenvironment, for example metformin, senolytics or others might indirectly improve macrophage function during aging. Overall design: Four bisulfite-Seq (reduced representation) of flow sorting of alveolar macrophages from mice treated with bone marrow chimeras to allow knowing the origin of pulmonary macrophages (TRAMs vs. Mo-AMs)