Age Mosaicism across Multiple Scales in Adult Tissues

• Published in: Cell metabolism 2019-08, Vol.30 (2), p.343-351.e3
• Main Authors: Arrojo e Drigo, Rafael, Lev-Ram, Varda, Tyagi, Swati, Ramachandra, Ranjan, Deerinck, Thomas, Bushong, Eric, Phan, Sebastien, Orphan, Victoria, Lechene, Claude, Ellisman, Mark H., Hetzer, Martin W.
• Format: Article
• Language: English
• Subjects: aging; Cell Biology; cell longevity; correlated multi-scale multi-modal microscopy; Endocrinology & Metabolism; islets of Langerhans; multi-isotope imaging mass spectroscopy; primary cilium
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2019.05.010

Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using 15N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization. [Display omitted] •Isotope microscopy reveals age mosaicism of cells and specific protein complexes•Most hepatocytes are as old as neurons, while sinusoidal endothelial cells are young•Pancreatic alpha, beta, and delta cells can be as old as the animal they reside in•Components of the beta cell primary cilium last a lifetime Arrojo e Drigo et al. measure the age of cells and proteins using high-resolution isotope imaging and show that adult mouse organs are mosaics of cells of different ages. The liver, which has high turnover, contains cells as old as the animal, while cilia have differentially aged structural protein components.