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Stem cell aging: mechanisms, regulators and therapeutic opportunities

Abstract

Aging tissues experience a progressive decline in homeostatic and regenerative capacities, which has been attributed to degenerative changes in tissue-specific stem cells, stem cell niches and systemic cues that regulate stem cell activity. Understanding the molecular pathways involved in this age-dependent deterioration of stem cell function will be critical for developing new therapies for diseases of aging that target the specific causes of age-related functional decline. Here we explore key molecular pathways that are commonly perturbed as tissues and stem cells age and degenerate. We further consider experimental evidence both suppoxrting and refuting the notion that modulation of these pathways per se can reverse aging phenotypes. Finally, we ask whether stem cell aging establishes an epigenetic 'memory' that is indelibly written or one that can be reset.

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Figure 1: Common pathways contributing to stem cell loss and dysfunction in the aging process.

Debbie Maizels / Nature Publishing Group

Figure 2: The effects of DNA damage in the aging genome that may affect stem cell function.

Debbie Maizels / Nature Publishing Group

Figure 3: Signaling pathways involved in aging of stem cells.

Debbie Maizels / Nature Publishing Group

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Acknowledgements

We thank all members of the Wagers laboratory for advice and comments during the preparation of this article. This work was funded in part by US National Cancer Institute grant T32CA-0216 from the Massachusetts General Hospital Department of Pathology (Y.D.L.), by US National Institutes of Health (NIH) grant T32DK007260 (J.O.), and by NIH grants 1R01 AG033053 and 5U01 HL100402 and the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging (A.J.W.). A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies.

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Oh, J., Lee, Y. & Wagers, A. Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med 20, 870–880 (2014). https://doi.org/10.1038/nm.3651

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