Aging of hematopoietic stem cells: DNA damage and mutations?
Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a si...
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Veröffentlicht in: | Experimental hematology 2016-10, Vol.44 (10), p.895-901 |
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description | Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly larger amount of γH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared with young cells, and bone marrow failure in animals devoid of DNA repair factors. Novel data on the increase in and nature of DNA mutations in the hematopoietic system with age, the quality of the DNA damage response in aged HSCs, and the nature of γH2AX foci question a direct link between DNA damage and the DNA damage response and aging of HSCs, and rather favor changes in epigenetics, splicing-factors or three-dimensional architecture of the cell as major cell intrinsic factors of HSCs aging. Aging of HSCs is also driven by a strong contribution of aging of the niche. This review discusses the DNA damage theory of HSC aging in the light of these novel mechanisms of aging of HSCs. |
doi_str_mv | 10.1016/j.exphem.2016.06.253 |
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This review discusses the DNA damage theory of HSC aging in the light of these novel mechanisms of aging of HSCs.</description><subject>Advanced Basic Science</subject><subject>Aging</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Cycle</subject><subject>Cell Differentiation</subject><subject>Cellular Senescence - genetics</subject><subject>DNA Damage</subject><subject>Epigenesis, Genetic</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hematopoiesis</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Mutation</subject><subject>Oxidative Stress</subject><issn>0301-472X</issn><issn>1873-2399</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhHyCUI5eEsR07DkKgVfmUKjgAEreR40y2XpJ4GycV_fc42lI-LpxG1rzzjud5GXvMoeDA9bN9QT8OFzQUIr0K0IVQ8g7bcFPJXMi6vss2IIHnZSW-nbAHMe4BQKka7rMTUZWQ5NWGvdju_LjLQpclKzuHQ_A0e5fFmYbMUd_H59nrj9ustYPdUWbHNhuW2c4-jPHVQ3avs32kRzf1lH19--bL2fv8_NO7D2fb89wpU845l7oEZ3kHRuiurIio41KVzjRdV9Wl0rrmpKxpGiEcmYoa3jWtMdxK0lzLU_by6HtYmoFaR-M82R4Pkx_sdI3Bevy7M_oL3IUrVCCVhioZPL0xmMLlQnHGwcf1OjtSWCJyIyRIzrVK0vIodVOIcaLudg0HXMHjHo_gcQWPoDGRTGNP_vzi7dAv0r9voATqytOE0XkaHbV-IjdjG_z_Nvxr4Ho_emf773RNcR-WaUwhIMcoEPDzGv6afeIHpTJc_gQC4atm</recordid><startdate>20161001</startdate><enddate>20161001</enddate><creator>Moehrle, Bettina M</creator><creator>Geiger, Hartmut</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161001</creationdate><title>Aging of hematopoietic stem cells: DNA damage and mutations?</title><author>Moehrle, Bettina M ; Geiger, Hartmut</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-13640ca1f0826f47eeef1354c8bff79456691e5a8bb22ce87eb1fbd881a3e6163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Advanced Basic Science</topic><topic>Aging</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cell Cycle</topic><topic>Cell Differentiation</topic><topic>Cellular Senescence - genetics</topic><topic>DNA Damage</topic><topic>Epigenesis, Genetic</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hematopoiesis</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Mutation</topic><topic>Oxidative Stress</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moehrle, Bettina M</creatorcontrib><creatorcontrib>Geiger, Hartmut</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moehrle, Bettina M</au><au>Geiger, Hartmut</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aging of hematopoietic stem cells: DNA damage and mutations?</atitle><jtitle>Experimental hematology</jtitle><addtitle>Exp Hematol</addtitle><date>2016-10-01</date><risdate>2016</risdate><volume>44</volume><issue>10</issue><spage>895</spage><epage>901</epage><pages>895-901</pages><issn>0301-472X</issn><eissn>1873-2399</eissn><abstract>Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. 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subjects | Advanced Basic Science Aging Animals Apoptosis Cell Cycle Cell Differentiation Cellular Senescence - genetics DNA Damage Epigenesis, Genetic Hematology, Oncology and Palliative Medicine Hematopoiesis Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Humans Mutation Oxidative Stress |
title | Aging of hematopoietic stem cells: DNA damage and mutations? |
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