Aging and senescence-associated signatures of aged kidney glomerular cells [scRNA-seq]

The kidney governs many physiological factors of the body, and the glomerulus is its core filtration unit. Glomeruli comprise of less than 1.5% of the kidney’s volume and thus are underrepresented in many analyses of the kidney, and require particular isolation methods. Aging is a major risk factor for kidney disease, yet despite the importance of proper glomerular function, we have limited knowledge of the changes that glomerular cells undergo during aging. Here we interrogate the aged mouse kidney, glomerulus and glomerular cells using various approaches, including single cell RNA sequencing (scRNA-Seq), to identify age and senescence associated changes at the tissue and cellular level. We show that the aged kidney and glomerulus undergo structural changes, including increased fibrosis, glomerulonephritis and expression of injury and senescence-associated markers. Lastly, we utilized our method for high-throughput analysis of mouse glomeruli to characterize cell-specific and age-related changes in glomerular cells. This analysis revealed a senescence-associated phenotype in aged mesangial cells, and emphasized the potential importance of mesangial cells and macrophages in this niche. Our study provides insights into the molecular and cellular changes of the aging glomerulus that suggest therapeutic targets for age-related renal dysfunction.