期刊
CELL STEM CELL
卷 22, 期 5, 页码 769-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2018.04.001
关键词
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资金
- NIH [R00 AG045144, R01 CA211184, R01 CA034992, R01 CA103866, K99 AG054760, R01 AG033082, R01 NS065874]
- V Foundation V Scholar Award [6930750]
- Sidney Kimmel Scholar Award [6934241]
- MIT Stem Cell Initiative through Fondation MIT
- Pew-Stewart Trust Scholar Award [025887-00001]
- Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund
- American Federation of Aging Research (AFAR) [6932237]
- Glenn/AFAR Breakthroughs in Gerontology Award [6932237]
- Damon Runyon Postdoctoral Fellowship [DRG 2146-13]
- Ludwig Postdoctoral Fellowship [2036238]
- Ludwig Postdoctoral Fellowship
- Helen Hay Whitney Postdoctoral Fellowship [16123046/2389185]
- Koch Institute from the National Cancer Institute [P30-CA14051]
Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration.
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