Short-term intensive fasting improves red blood cell function and rejuvenates erythropoiesis via regulating MS4A3-CDK2 module

Abstract

Fasting is known to improve health, but the precisely beneficial effects of specific types of fasting and their underlying mechanisms are not fully understood. We herein report that in humans, occasional short-term intensive fasting (STIF), a traditional fasting format favored by Asians, promotes erythropoiesis and boosts the function of red blood cells (RBCs) in oxygen transportation, ATP generation, antioxidant capacity, and innate immune response. The rejuvenation of erythropoiesis is more pronounced in humans with low RBC counts. Using mouse models and a human erythroid progenitor cell model, we found that occasional STIF rejuvenates erythropoiesis by enhancing megakaryocyte-erythroid progenitor selfrenewal and erythroid-biased differentiation without compromising normal hematopoiesis. Molecularly, STIF relies on an autophagy-dependent but erythropoietin (EPO) upregulation-independent MS4A3-CDK2 module to augment the production of RBCs. Our findings thus suggest that STIF can occasionally be practiced as an efficient noninvasive intervention for better erythropoiesis, particularly for adults with low RBC counts.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

ChiCTR1900027451

Funding Statement

National Natural Science Foundation of China by grants No.91649113, No.82170227 and No.31771640 (to JW)

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted with approval from the Institutional Ethics Review Board at Soochow University (Approval No. ECSU-2019000153) and the Chinese Clinical Trial Register, an official review board for clinical trials (Registration No. ChiCTR1900027451), affiliated with The Ministry of Public Health of China (http://www.chictr.org.cn/index.aspx).

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Data Availability

All data produced in the present work are contained in the manuscript

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