Cellular and Molecular Mechanisms Involved in Hematopoietic Stem Cell Aging As a Clinical Prospect

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2022 Apr 11

PMID 35401928

Authors

Soheila Montazersaheb

Ali Ehsani

Ezzatollah Fathi

Raheleh Farahzadi

Affiliations

Soon will be listed here.

Abstract

There is a hot topic in stem cell research to investigate the process of hematopoietic stem cell (HSC) aging characterized by decreased self-renewal ability, myeloid-biased differentiation, impaired homing, and other abnormalities related to hematopoietic repair function. It is of crucial importance that HSCs preserve self-renewal and differentiation ability to maintain hematopoiesis under homeostatic states over time. Although HSC numbers increase with age in both mice and humans, this cannot compensate for functional defects of aged HSCs. The underlying mechanisms regarding HSC aging have been studied from various perspectives, but the exact molecular events remain unclear. Several cell-intrinsic and cell-extrinsic factors contribute to HSC aging including DNA damage responses, reactive oxygen species (ROS), altered epigenetic profiling, polarity, metabolic alterations, impaired autophagy, Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, nuclear factor- (NF-) B pathway, mTOR pathway, transforming growth factor-beta (TGF-) pathway, and wingless-related integration site (Wnt) pathway. To determine how deficient HSCs develop during aging, we provide an overview of different hallmarks, age-related signaling pathways, and epigenetic modifications in young and aged HSCs. Knowing how such changes occur and progress will help researchers to develop medications and promote the quality of life for the elderly and possibly alleviate age-associated hematopoietic disorders. The present review is aimed at discussing the latest advancements of HSC aging and the role of HSC-intrinsic factors and related events of a bone marrow niche during HSC aging.

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References

Verovskaya E, Dellorusso P, Passegue E . Losing Sense of Self and Surroundings: Hematopoietic Stem Cell Aging and Leukemic Transformation. Trends Mol Med. 2019; 25(6):494-515. PMC: 7657013. DOI: 10.1016/j.molmed.2019.04.006. View

Chen F, Liu Y, Wong N, Xiao J, So K . Oxidative Stress in Stem Cell Aging. Cell Transplant. 2017; 26(9):1483-1495. PMC: 5680960. DOI: 10.1177/0963689717735407. View

Liang Y, van Zant G, Szilvassy S . Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood. 2005; 106(4):1479-87. PMC: 1895199. DOI: 10.1182/blood-2004-11-4282. View

Flach J, Bakker S, Mohrin M, Conroy P, Pietras E, Reynaud D . Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature. 2014; 512(7513):198-202. PMC: 4456040. DOI: 10.1038/nature13619. View

Ho T, Warr M, Adelman E, Lansinger O, Flach J, Verovskaya E . Autophagy maintains the metabolism and function of young and old stem cells. Nature. 2017; 543(7644):205-210. PMC: 5344718. DOI: 10.1038/nature21388. View

Chen D, Kerr C . The Epigenetics of Stem Cell Aging Comes of Age. Trends Cell Biol. 2019; 29(7):563-568. PMC: 7144731. DOI: 10.1016/j.tcb.2019.03.006. View

Geiger H, Rudolph K . Aging in the lympho-hematopoietic stem cell compartment. Trends Immunol. 2009; 30(7):360-5. DOI: 10.1016/j.it.2009.03.010. View

Pang W, Price E, Sahoo D, Beerman I, Maloney W, Rossi D . Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci U S A. 2011; 108(50):20012-7. PMC: 3250139. DOI: 10.1073/pnas.1116110108. View

Talukdar S, Das S, Emdad L, Fisher P . Autophagy and senescence: Insights from normal and cancer stem cells. Adv Cancer Res. 2021; 150:147-208. DOI: 10.1016/bs.acr.2021.01.005. View

10.

Chandel N, Jasper H, Ho T, Passegue E . Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing. Nat Cell Biol. 2016; 18(8):823-32. DOI: 10.1038/ncb3385. View

11.

Genovese G, Kahler A, Handsaker R, Lindberg J, Rose S, Bakhoum S . Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014; 371(26):2477-87. PMC: 4290021. DOI: 10.1056/NEJMoa1409405. View

12.

Lu L, Wang Y, Zhang J, Li D, Meng A . p38 MAPK Inhibitor Insufficiently Attenuates HSC Senescence Administered Long-Term after 6 Gy Total Body Irradiation in Mice. Int J Mol Sci. 2016; 17(6). PMC: 4926439. DOI: 10.3390/ijms17060905. View

13.

Liu F, Poursine-Laurent J, Link D . Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF. Blood. 2000; 95(10):3025-31. View

14.

Maryanovich M, Zahalka A, Pierce H, Pinho S, Nakahara F, Asada N . Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat Med. 2018; 24(6):782-791. PMC: 6095812. DOI: 10.1038/s41591-018-0030-x. View

15.

Bernitz J, Rapp K, Daniel M, Shcherbinin D, Yuan Y, Gomes A . Memory of Divisional History Directs the Continuous Process of Primitive Hematopoietic Lineage Commitment. Stem Cell Reports. 2020; 14(4):561-574. PMC: 7160360. DOI: 10.1016/j.stemcr.2020.03.005. View

16.

Kunimoto H, Nakajima H . Epigenetic dysregulation of hematopoietic stem cells and preleukemic state. Int J Hematol. 2017; 106(1):34-44. DOI: 10.1007/s12185-017-2257-6. View

17.

Chen C, Liu Y, Liu Y, Zheng P . mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal. 2009; 2(98):ra75. PMC: 4020596. DOI: 10.1126/scisignal.2000559. View

18.

Bruns I, Lucas D, Pinho S, Ahmed J, Lambert M, Kunisaki Y . Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nat Med. 2014; 20(11):1315-20. PMC: 4258871. DOI: 10.1038/nm.3707. View

19.

Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman I, Bryder D . Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A. 2010; 107(12):5465-70. PMC: 2851806. DOI: 10.1073/pnas.1000834107. View

20.

McNeely T, Leone M, Yanai H, Beerman I . DNA damage in aging, the stem cell perspective. Hum Genet. 2019; 139(3):309-331. PMC: 6980431. DOI: 10.1007/s00439-019-02047-z. View