Updates on Old and Weary Haematopoiesis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Aug 31

PMID 30158459

Citations 10

Authors

Joanna Konieczny

Lorena Arranz

Affiliations

Soon will be listed here.

Abstract

Blood formation, or haematopoiesis, originates from haematopoietic stem cells (HSCs), whose functions and maintenance are regulated in both cell- and cell non-autonomous ways. The surroundings of HSCs in the bone marrow create a specific niche or microenvironment where HSCs nest that allows them to retain their unique characteristics and respond rapidly to external stimuli. Ageing is accompanied by reduced regenerative capacity of the organism affecting all systems, due to the progressive decline of stem cell functions. This includes blood and HSCs, which contributes to age-related haematological disorders, anaemia, and immunosenescence, among others. Furthermore, chronological ageing is characterised by myeloid and platelet HSC skewing, inflammageing, and expanded clonal haematopoiesis, which may be the result of the accumulation of preleukaemic lesions in HSCs. Intriguingly, haematological malignancies such as acute myeloid leukaemia have a high incidence among elderly patients, yet not all individuals with clonal haematopoiesis develop leukaemias. Here, we discuss recent work on these aspects, their potential underlying molecular mechanisms, and the first cues linking age-related changes in the HSC niche to poor HSC maintenance. Future work is needed for a better understanding of haematopoiesis during ageing. This field may open new avenues for HSC rejuvenation and therapeutic strategies in the elderly.

Citing Articles

Biomarkers of aging.

Bao H, Cao J, Chen M, Chen M, Chen W, Chen X Sci China Life Sci. 2023; 66(5):893-1066.

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Mosaic Chromosomal Alterations and Human Longevity.

Leshchyk A, Xiang Q, Andersen S, Gurinovich A, Song Z, Lee J J Gerontol A Biol Sci Med Sci. 2023; 78(9):1561-1568.

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Somatic Mutations of Hematopoietic Cells Are an Additional Mechanism of Body Aging, Conducive to Comorbidity and Increasing Chronification of Inflammation.

Yegorov Y, Poznyak A, Bezsonov E, Zhuravlev A, Nikiforov N, Vishnyakova K Biomedicines. 2022; 10(4).

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How Immunosenescence and Inflammaging May Contribute to Hyperinflammatory Syndrome in COVID-19.

Muller L, Di Benedetto S Int J Mol Sci. 2021; 22(22).

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JAK-STAT in Early Hematopoiesis and Leukemia.

Fasouli E, Katsantoni E Front Cell Dev Biol. 2021; 9:669363.

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References

Schroeder T . Hematopoietic stem cell heterogeneity: subtypes, not unpredictable behavior. Cell Stem Cell. 2010; 6(3):203-7. DOI: 10.1016/j.stem.2010.02.006. View

Sperka T, Wang J, Rudolph K . DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev Mol Cell Biol. 2012; 13(9):579-90. DOI: 10.1038/nrm3420. View

Tyner S, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H . p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002; 415(6867):45-53. DOI: 10.1038/415045a. View

Notta F, Zandi S, Takayama N, Dobson S, Gan O, Wilson G . Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science. 2015; 351(6269):aab2116. PMC: 4816201. DOI: 10.1126/science.aab2116. View

Yasuda T, Ueno T, Fukumura K, Yamato A, Ando M, Yamaguchi H . Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation. Leukemia. 2013; 28(2):426-8. DOI: 10.1038/leu.2013.278. View

Franceschi C, Campisi J . Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014; 69 Suppl 1:S4-9. DOI: 10.1093/gerona/glu057. View

Dong L, Yu W, Zheng H, Loh M, Bunting S, Pauly M . Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment. Nature. 2016; 539(7628):304-308. PMC: 5317374. DOI: 10.1038/nature20131. View

Pietras E, Reynaud D, Kang Y, Carlin D, Calero-Nieto F, Leavitt A . Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions. Cell Stem Cell. 2015; 17(1):35-46. PMC: 4542150. DOI: 10.1016/j.stem.2015.05.003. View

Dykstra B, Olthof S, Schreuder J, Ritsema M, de Haan G . Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med. 2011; 208(13):2691-703. PMC: 3244040. DOI: 10.1084/jem.20111490. View

10.

Young K, Borikar S, Bell R, Kuffler L, Philip V, Trowbridge J . Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging. J Exp Med. 2016; 213(11):2259-2267. PMC: 5068232. DOI: 10.1084/jem.20160168. View

11.

Bernal A, Arranz L . Nestin-expressing progenitor cells: function, identity and therapeutic implications. Cell Mol Life Sci. 2018; 75(12):2177-2195. PMC: 5948302. DOI: 10.1007/s00018-018-2794-z. View

12.

Grover A, Sanjuan-Pla A, Thongjuea S, Carrelha J, Giustacchini A, Gambardella A . Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells. Nat Commun. 2016; 7:11075. PMC: 4820843. DOI: 10.1038/ncomms11075. View

13.

Vaziri H, Dragowska W, Allsopp R, Thomas T, Harley C, Lansdorp P . Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A. 1994; 91(21):9857-60. PMC: 44916. DOI: 10.1073/pnas.91.21.9857. View

14.

Raval A, Behbehani G, Truong Nguyen L, Thomas D, Kusler B, Garbuzov A . Reversibility of Defective Hematopoiesis Caused by Telomere Shortening in Telomerase Knockout Mice. PLoS One. 2015; 10(7):e0131722. PMC: 4489842. DOI: 10.1371/journal.pone.0131722. View

15.

Hosokawa K, MacArthur B, Ikushima Y, Toyama H, Masuhiro Y, Hanazawa S . The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. Nat Commun. 2017; 8(1):804. PMC: 5630588. DOI: 10.1038/s41467-017-00935-4. View

16.

Pietras E, Mirantes-Barbeito C, Fong S, Loeffler D, Kovtonyuk L, Zhang S . Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nat Cell Biol. 2016; 18(6):607-18. PMC: 4884136. DOI: 10.1038/ncb3346. View

17.

Abelson S, Collord G, Ng S, Weissbrod O, Mendelson Cohen N, Niemeyer E . Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018; 559(7714):400-404. PMC: 6485381. DOI: 10.1038/s41586-018-0317-6. View

18.

Hanoun M, Zhang D, Mizoguchi T, Pinho S, Pierce H, Kunisaki Y . Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche. Cell Stem Cell. 2014; 15(3):365-375. PMC: 4156919. DOI: 10.1016/j.stem.2014.06.020. View

19.

Haas S, Hansson J, Klimmeck D, Loeffler D, Velten L, Uckelmann H . Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors. Cell Stem Cell. 2015; 17(4):422-34. DOI: 10.1016/j.stem.2015.07.007. View

20.

Hasselbalch H . The platelet-cancer loop in myeloproliferative cancer. Is thrombocythemia an enhancer of cancer invasiveness and metastasis in essential thrombocythemia, polycythemia vera and myelofibrosis?. Leuk Res. 2014; 38(10):1230-6. DOI: 10.1016/j.leukres.2014.07.006. View