Aging, Hematopoiesis, and the Myelodysplastic Syndromes

Overview

Journal Blood Adv

Specialty Hematology

Date 2018 Jan 4

PMID 29296910

Citations 16

Authors

Stephen S Chung

Christopher Y Park

Affiliations

Soon will be listed here.

Abstract

The aging hematopoietic system undergoes numerous changes, including reduced production of red blood cells and lymphocytes as well as a relative increase in the production of myeloid cells. Emerging evidence indicates that many of these changes are due to selection pressures from cell-intrinsic and cell-extrinsic factors that result in clonal shifts in the hematopoietic stem cell (HSC) pool, resulting in predominant HSC clones that exhibit the functional characteristics associated with HSC aging. Given the recent descriptions of clonal hematopoiesis in aged populations, the increased risk of developing hematologic malignancies in individuals with clonal hematopoiesis, and the many similarities in hematopoietic aging and acquired bone marrow failure (BMF) syndromes, such as myelodysplastic syndromes (MDS), this raises significant questions regarding the relationship between aging hematopoiesis and MDS, including the factors that regulate HSC aging, whether clonal hematopoiesis is required for the development of MDS, and even whether BMF is an inevitable consequence of aging. In this article, we will review our current understanding of these processes and the potential intersections among them.

Citing Articles

Single-cell transcriptomics identifies the common perturbations of monocyte/macrophage lineage cells in inflammaging of bone marrow.

Liao P, Tong S, Du L, Mei J, Wang B, Lu Y J Orthop Translat. 2025; 50:85-96.

PMID: 39868348 PMC: 11762928. DOI: 10.1016/j.jot.2024.09.013.

Immunoaging - the effect of age on serum levels of NET biomarkers in men: a pilot study.

Garley M, Omeljaniuk W, Motkowski R, Ratajczak-Wrona W, Jablonska E, Filipkowski D Int J Occup Med Environ Health. 2023; 36(3):333-348.

PMID: 37681423 PMC: 10664002. DOI: 10.13075/ijomeh.1896.02125.

Inflammation and aging: signaling pathways and intervention therapies.

Li X, Li C, Zhang W, Wang Y, Qian P, Huang H Signal Transduct Target Ther. 2023; 8(1):239.

PMID: 37291105 PMC: 10248351. DOI: 10.1038/s41392-023-01502-8.

Genome-wide analysis toward the epigenetic aetiology of myelodysplastic syndrome disease progression and pharmacoepigenomic basis of hypomethylating agents drug treatment response.

Siamoglou S, Boers R, Koromina M, Boers J, Tsironi A, Chatzilygeroudi T Hum Genomics. 2023; 17(1):37.

PMID: 37098643 PMC: 10127336. DOI: 10.1186/s40246-023-00483-7.

Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia.

Wang Z, Zhang C, Warden C, Liu Z, Yuan Y, Guo C Commun Biol. 2022; 5(1):396.

PMID: 35484199 PMC: 9051098. DOI: 10.1038/s42003-022-03340-w.

References

Adams P, Jasper H, Rudolph K . Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer. Cell Stem Cell. 2015; 16(6):601-12. PMC: 4509784. DOI: 10.1016/j.stem.2015.05.002. View

Mohrin M, Bourke E, Alexander D, Warr M, Barry-Holson K, Le Beau M . Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell. 2010; 7(2):174-85. PMC: 2924905. DOI: 10.1016/j.stem.2010.06.014. View

Fuster J, MacLauchlan S, Zuriaga M, Polackal M, Ostriker A, Chakraborty R . Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017; 355(6327):842-847. PMC: 5542057. DOI: 10.1126/science.aag1381. View

Park C . Hematopoiesis in aging: Current concepts and challenges. Semin Hematol. 2017; 54(1):1-3. DOI: 10.1053/j.seminhematol.2016.10.007. View

Sun D, Luo M, Jeong M, Rodriguez B, Xia Z, Hannah R . Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell. 2014; 14(5):673-88. PMC: 4070311. DOI: 10.1016/j.stem.2014.03.002. View

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

Steensma D, Bejar R, Jaiswal S, Lindsley R, Sekeres M, Hasserjian R . Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015; 126(1):9-16. PMC: 4624443. DOI: 10.1182/blood-2015-03-631747. View

Theocharides A, Rongvaux A, Fritsch K, Flavell R, Manz M . Humanized hemato-lymphoid system mice. Haematologica. 2016; 101(1):5-19. PMC: 4697887. DOI: 10.3324/haematol.2014.115212. View

Beerman I, Seita J, Inlay M, Weissman I, Rossi D . Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle. Cell Stem Cell. 2014; 15(1):37-50. PMC: 4082747. DOI: 10.1016/j.stem.2014.04.016. View

10.

Tomasetti C, Vogelstein B . Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015; 347(6217):78-81. PMC: 4446723. DOI: 10.1126/science.1260825. View

11.

Pang W, Pluvinage J, Price E, Sridhar K, Arber D, Greenberg P . Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes. Proc Natl Acad Sci U S A. 2013; 110(8):3011-6. PMC: 3581956. DOI: 10.1073/pnas.1222861110. View

12.

Damm F, Mylonas E, Cosson A, Yoshida K, Valle V, Mouly E . Acquired initiating mutations in early hematopoietic cells of CLL patients. Cancer Discov. 2014; 4(9):1088-101. DOI: 10.1158/2159-8290.CD-14-0104. View

13.

Flores-Figueroa E, Arana-Trejo R, Gutierrez-Espindola G, Perez-Cabrera A, Mayani H . Mesenchymal stem cells in myelodysplastic syndromes: phenotypic and cytogenetic characterization. Leuk Res. 2004; 29(2):215-24. DOI: 10.1016/j.leukres.2004.06.011. View

14.

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

15.

Elias H, Bryder D, Park C . Molecular mechanisms underlying lineage bias in aging hematopoiesis. Semin Hematol. 2017; 54(1):4-11. DOI: 10.1053/j.seminhematol.2016.11.002. View

16.

Geiger H, de Haan G, Florian M . The ageing haematopoietic stem cell compartment. Nat Rev Immunol. 2013; 13(5):376-89. DOI: 10.1038/nri3433. View

17.

Makipour S, Kanapuru B, Ershler W . Unexplained anemia in the elderly. Semin Hematol. 2008; 45(4):250-4. PMC: 2586804. DOI: 10.1053/j.seminhematol.2008.06.003. View

18.

Jaiswal S, Natarajan P, Silver A, Gibson C, Bick A, Shvartz E . Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med. 2017; 377(2):111-121. PMC: 6717509. DOI: 10.1056/NEJMoa1701719. View

19.

Denkinger M, Leins H, Schirmbeck R, Florian M, Geiger H . HSC Aging and Senescent Immune Remodeling. Trends Immunol. 2015; 36(12):815-824. PMC: 4710174. DOI: 10.1016/j.it.2015.10.008. View

20.

Young N . Current concepts in the pathophysiology and treatment of aplastic anemia. Hematology Am Soc Hematol Educ Program. 2013; 2013:76-81. PMC: 6610029. DOI: 10.1182/asheducation-2013.1.76. View