Rejuvenation of aged progenitor cells by exposure to a young systemic environment
The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem cells. A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in...
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| Veröffentlicht in: | Nature 2005-02, Vol.433 (7027), p.760-764 |
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| description | The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem cells. A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged progenitor cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite cells. The exposure of satellite cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age. |
| doi_str_mv | 10.1038/nature03260 |
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A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged progenitor cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite cells. The exposure of satellite cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature03260</identifier><identifier>PMID: 15716955</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Ageing, cell death ; Aging ; Aging - physiology ; Animals ; Biological and medical sciences ; CCAAT-Enhancer-Binding Protein-alpha - metabolism ; Cell Cycle Proteins - metabolism ; Cell physiology ; Cell Proliferation ; Cells ; Cellular biology ; Cellular Senescence - physiology ; Drosophila Proteins ; Extracellular Space - physiology ; Fundamental and applied biological sciences. Psychology ; Hepatocytes - cytology ; Hepatocytes - metabolism ; Liver ; Liver - cytology ; Liver - physiology ; Liver Regeneration - physiology ; Membrane Proteins - metabolism ; Mice ; Mice, Inbred C57BL ; Molecular and cellular biology ; Muscles - cytology ; Muscles - injuries ; Muscles - pathology ; Muscles - physiology ; Organ Specificity ; Receptors, Notch ; Regeneration - physiology ; Satellite Cells, Skeletal Muscle - cytology ; Satellite Cells, Skeletal Muscle - physiology ; Signal Transduction ; Stem cells ; Trans-Activators - metabolism</subject><ispartof>Nature, 2005-02, Vol.433 (7027), p.760-764</ispartof><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. Feb 17, 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c607t-f55e526036e99da9f7698236b96198b83bb791057c3c34fc7815f0a2e6d140c13</citedby><cites>FETCH-LOGICAL-c607t-f55e526036e99da9f7698236b96198b83bb791057c3c34fc7815f0a2e6d140c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2728,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16527308$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15716955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rando, Thomas A</creatorcontrib><creatorcontrib>Conboy, Irina M</creatorcontrib><creatorcontrib>Conboy, Michael J</creatorcontrib><creatorcontrib>Wagers, Amy J</creatorcontrib><creatorcontrib>Girma, Eric R</creatorcontrib><creatorcontrib>Weissman, Irving L</creatorcontrib><title>Rejuvenation of aged progenitor cells by exposure to a young systemic environment</title><title>Nature</title><addtitle>Nature</addtitle><description>The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem cells. A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged progenitor cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite cells. The exposure of satellite cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age.</description><subject>Ageing, cell death</subject><subject>Aging</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>CCAAT-Enhancer-Binding Protein-alpha - metabolism</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell physiology</subject><subject>Cell Proliferation</subject><subject>Cells</subject><subject>Cellular biology</subject><subject>Cellular Senescence - physiology</subject><subject>Drosophila Proteins</subject><subject>Extracellular Space - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - metabolism</subject><subject>Liver</subject><subject>Liver - cytology</subject><subject>Liver - physiology</subject><subject>Liver Regeneration - physiology</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular and cellular biology</subject><subject>Muscles - cytology</subject><subject>Muscles - injuries</subject><subject>Muscles - pathology</subject><subject>Muscles - physiology</subject><subject>Organ Specificity</subject><subject>Receptors, Notch</subject><subject>Regeneration - physiology</subject><subject>Satellite Cells, Skeletal Muscle - cytology</subject><subject>Satellite Cells, Skeletal Muscle - physiology</subject><subject>Signal Transduction</subject><subject>Stem cells</subject><subject>Trans-Activators - metabolism</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF0l2LEzEUBuAgilurV95LXFARmTWZfF-W4sfCoriueDlk0jNlyjTpJjPL9t-b0mJbqcpcDAzPvOfk5CD0nJILSph-720_RCCslOQBGlGuZMGlVg_RiJBSF0QzeYaepLQghAiq-GN0RoWi0ggxQt-uYTHcQc5og8ehwXYOM7yKYQ6-7UPEDrou4XqN4X4VUi6E-4AtXofBz3Fapx6WrcPg79oY_BJ8_xQ9amyX4NnuPUY_Pn64mX4urr5-upxOrgonieqLRggQuWUmwZiZNY2SRpdM1kZSo2vN6loZSoRyzDHeOKWpaIgtQc4oJ46yMXqzzc3N3g6Q-mrZpk231kMYUqU441RwQ7J8_U8pM9VlWf4XUqU4LaXJ8PwPuAhD9Pm4VUm4MFLqTdlii-a2g6r1TeijdXmuEG0XPDRt_jyhWnBFtVb70CPvVu1tdYguTqD8zDb3cDL17dEP2fRw38_tkFJ1-f362L77u53c_Jx-OaldDClFaKpVbJc2ritKqs1mVgebmfWL3ciGegmzvd2tYgavdsAmZ7smWu_atHdSlIrlZR6jl1u3Tf8NDov9AtYO8vo</recordid><startdate>20050217</startdate><enddate>20050217</enddate><creator>Rando, Thomas A</creator><creator>Conboy, Irina M</creator><creator>Conboy, Michael J</creator><creator>Wagers, Amy J</creator><creator>Girma, Eric R</creator><creator>Weissman, Irving L</creator><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</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>ATWCN</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope></search><sort><creationdate>20050217</creationdate><title>Rejuvenation of aged progenitor cells by exposure to a young systemic environment</title><author>Rando, Thomas A ; 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A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged progenitor cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite cells. The exposure of satellite cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>15716955</pmid><doi>10.1038/nature03260</doi><tpages>5</tpages></addata></record> |
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| ispartof | Nature, 2005-02, Vol.433 (7027), p.760-764 |
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| language | eng |
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| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Ageing, cell death Aging Aging - physiology Animals Biological and medical sciences CCAAT-Enhancer-Binding Protein-alpha - metabolism Cell Cycle Proteins - metabolism Cell physiology Cell Proliferation Cells Cellular biology Cellular Senescence - physiology Drosophila Proteins Extracellular Space - physiology Fundamental and applied biological sciences. Psychology Hepatocytes - cytology Hepatocytes - metabolism Liver Liver - cytology Liver - physiology Liver Regeneration - physiology Membrane Proteins - metabolism Mice Mice, Inbred C57BL Molecular and cellular biology Muscles - cytology Muscles - injuries Muscles - pathology Muscles - physiology Organ Specificity Receptors, Notch Regeneration - physiology Satellite Cells, Skeletal Muscle - cytology Satellite Cells, Skeletal Muscle - physiology Signal Transduction Stem cells Trans-Activators - metabolism |
| title | Rejuvenation of aged progenitor cells by exposure to a young systemic environment |
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