Age Mosaicism across Multiple Scales in Adult Tissues.

Arrojo E Drigo R, Lev-Ram V, Tyagi S, Ramachandra R, Deerinck T, Bushong E, Phan S, Orphan V, Lechene C, Ellisman MH, Hetzer MW
Cell Metab. 2019 30 (2): 343-351.e3

PMID: 31178361 · PMCID: PMC7289515 · 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 N 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.

Copyright © 2019 Elsevier Inc. All rights reserved.

MeSH Terms (15)

Aging Animals Cellular Senescence Cilia Endothelial Cells Female Fibroblasts Insulin-Secreting Cells Liver Mice Mice, Inbred Strains Mosaicism Neurons Organ Specificity Pancreas

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