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Cell Metab. 2019 Aug 6;30(2):343-351.e3. doi: 10.1016/j.cmet.2019.05.010. Epub 2019 Jun 6.

Age Mosaicism across Multiple Scales in Adult Tissues.

Author information

1
Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory (MCBL), La Jolla, CA, USA.
2
Department of Pharmacology, University of California, San Diego School of Medicine (UCSD), La Jolla, CA, USA.
3
National Center for Microscopy and Imaging Research (NCMIR), University of California, San Diego (UCSD), La Jolla, CA, USA.
4
Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA, USA.
5
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
6
Department of Pharmacology, University of California, San Diego School of Medicine (UCSD), La Jolla, CA, USA; Department of Neurosciences, University of California, San Diego School of Medicine (UCSD), La Jolla, CA, USA.
7
Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory (MCBL), La Jolla, CA, USA. Electronic address: hetzer@salk.edu.

Abstract

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.

KEYWORDS:

aging; cell longevity; correlated multi-scale multi-modal microscopy; islets of Langerhans; multi-isotope imaging mass spectroscopy; primary cilium

PMID:
31178361
DOI:
10.1016/j.cmet.2019.05.010

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