Tissue cell-type composition changes during aging in mice

Abstract

Aging is linked to progressive alterations in organ functionality and a heightened susceptibility to various diseases. These age-related functional deteriorations are likely, in part, due to microstructural changes within organs, even in the absence of pathological conditions. Examining cellular composition at the organ-level across tissues traditionally posed significant challenges due to the high workload associated with the application of unbiased cell counting methods across a range of histological samples. Here, we employed bulk RNA-sequencing, coupled with deconvolution based on celltype specific markers, to generate datasets and derive estimates regarding agingassociated changes in cell-type composition across multiple tissues (brain, heart, lung, skeletal muscle, kidney, testis) in male C57BL/6J mice, covering much of their lifespan (3, 5, 8, 14, 20 and 26 month). We show that with advanced age, immune cell types showed predominant changes among all tested tissues. Across organs, most immune cells increased with advancing age while parenchymal cells showed a decreasing trend during aging. In addition, we mined publicly available RNA-seq datasets in mice to identify experimental conditions that either counteract or phenocopy aging-associated changes in cellular tissue composition. These analyses revealed, for instance, that diabetes phenocopies aging associated changes in the mouse kidney, and calorie restriction counteract aging in mice muscle. Additional well-established cell counting methodologies were used to confirm findings obtained using our deconvolution approach.