Journal
CELL METABOLISM
Volume 30, Issue 2, Pages 343-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2019.05.010
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Funding
- NIH Transformative Research Award [R01 NS096786]
- Keck Foundation
- NOMIS Foundation
- NIH NINDS [NIH RO1 NS027177-30]
- NIH NIGMS [5P41 GM103412-29]
- US Department of Energy, Office of Science, Office of Biological and Environmental Research [DE-SC0016469]
- American Diabetes Association postdoctoral fellowship [1-18-PMF-007]
- U.S. Department of Energy (DOE) [DE-SC0016469] Funding Source: U.S. Department of Energy (DOE)
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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( 15)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.
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