Stem cell secretome treatment improves whole‐body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice
Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a s...
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| Veröffentlicht in: | Aging cell 2024-06, Vol.23 (6), p.e14144-n/a |
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| creator | Fennel, Zachary J. Bourrant, Paul‐Emile Kurian, Anu Susan Petrocelli, Jonathan J. Hart, Naomi M. M. P. Yee, Elena M. Boudina, Sihem Keirstead, Hans S. Nistor, Gabrielle Greilach, Scott A. Berchtold, Nicole C. Lane, Thomas E. Drummond, Micah J. |
| description | Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22–24 months) compared to saline‐injected aged‐matched controls. Secretome delivery substantially increased whole‐body lean mass and decreased fat mass, corresponding to higher myofiber cross‐sectional area and smaller adipocyte size, respectively. Secretome‐treated mice also had greater whole‐body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome‐treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL‐6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome‐treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction. Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole‐body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice.
In this study, we show that the 4‐week administration of a stem cell secretome, made up of exosomes, growth, immune, and extracellular matrix factors, robustly ameliorated several hallmarks of aging in male mice resulting in improvements in physical function, metabolism, adiposity, and skeletal muscle remodeling. |
| doi_str_mv | 10.1111/acel.14144 |
| format | Article |
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In this study, we show that the 4‐week administration of a stem cell secretome, made up of exosomes, growth, immune, and extracellular matrix factors, robustly ameliorated several hallmarks of aging in male mice resulting in improvements in physical function, metabolism, adiposity, and skeletal muscle remodeling.</description><identifier>ISSN: 1474-9718</identifier><identifier>ISSN: 1474-9726</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.14144</identifier><identifier>PMID: 38500398</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adipocytes ; adipogenesis ; Adipose tissue ; Adiposity - drug effects ; Aging ; AKT protein ; Animals ; Body fat ; Cell culture ; Cell growth ; Cell size ; Collagen (type IV) ; Culture media ; Cytoskeleton ; Energy expenditure ; fibrosis ; Immunomodulation ; Kinases ; Lipids ; Male ; metabolic rate ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Myotubes ; NMR ; Nuclear magnetic resonance ; Phosphorylation ; Physical activity ; Quadriceps muscle ; sarcopenia ; Secretome ; Secretome - metabolism ; Skeletal muscle ; Stem cells ; Stem Cells - metabolism ; Vascular endothelial growth factor</subject><ispartof>Aging cell, 2024-06, Vol.23 (6), p.e14144-n/a</ispartof><rights>2024 The Authors. published by Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3524-a8acbcd9c75a859740debdba3fe1fbca2036aa329cd7a3ccadfa729d52d9822a3</cites><orcidid>0000-0001-5961-8890 ; 0000-0001-9482-7815</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Facel.14144$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Facel.14144$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,860,1411,11541,27901,27902,45550,45551,46027,46451</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38500398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fennel, Zachary J.</creatorcontrib><creatorcontrib>Bourrant, Paul‐Emile</creatorcontrib><creatorcontrib>Kurian, Anu Susan</creatorcontrib><creatorcontrib>Petrocelli, Jonathan J.</creatorcontrib><creatorcontrib>Hart, Naomi M. M. P.</creatorcontrib><creatorcontrib>Yee, Elena M.</creatorcontrib><creatorcontrib>Boudina, Sihem</creatorcontrib><creatorcontrib>Keirstead, Hans S.</creatorcontrib><creatorcontrib>Nistor, Gabrielle</creatorcontrib><creatorcontrib>Greilach, Scott A.</creatorcontrib><creatorcontrib>Berchtold, Nicole C.</creatorcontrib><creatorcontrib>Lane, Thomas E.</creatorcontrib><creatorcontrib>Drummond, Micah J.</creatorcontrib><title>Stem cell secretome treatment improves whole‐body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22–24 months) compared to saline‐injected aged‐matched controls. Secretome delivery substantially increased whole‐body lean mass and decreased fat mass, corresponding to higher myofiber cross‐sectional area and smaller adipocyte size, respectively. Secretome‐treated mice also had greater whole‐body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome‐treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL‐6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome‐treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction. Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole‐body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice.
In this study, we show that the 4‐week administration of a stem cell secretome, made up of exosomes, growth, immune, and extracellular matrix factors, robustly ameliorated several hallmarks of aging in male mice resulting in improvements in physical function, metabolism, adiposity, and skeletal muscle remodeling.</description><subject>Adipocytes</subject><subject>adipogenesis</subject><subject>Adipose tissue</subject><subject>Adiposity - drug effects</subject><subject>Aging</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Body fat</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell size</subject><subject>Collagen (type IV)</subject><subject>Culture media</subject><subject>Cytoskeleton</subject><subject>Energy expenditure</subject><subject>fibrosis</subject><subject>Immunomodulation</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Male</subject><subject>metabolic rate</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MicroRNAs</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Myotubes</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Phosphorylation</subject><subject>Physical activity</subject><subject>Quadriceps muscle</subject><subject>sarcopenia</subject><subject>Secretome</subject><subject>Secretome - metabolism</subject><subject>Skeletal muscle</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Vascular endothelial growth factor</subject><issn>1474-9718</issn><issn>1474-9726</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kbtuFDEUhi0EIhdoeABkiQahbPBlLnYZrUJAWokCqK0z9hlwsMfL2JNoOxp6npEnwcuGFBScxkfW50-_9RPyjLNzXuc1WAznvOFN84Ac86ZvVroX3cP7nasjcpLzNWO810w-JkdStYxJrY7Jjw8FI62CQDPaGUuKSMuMUCJOhfq4ndMNZnr7JQX89f3nkNyORiwwpOBzPKMzusVWAJzfpuzL7ozC5Gh9FlOp9_krhooHGpdsA9JxmWzxaaJ-ovAZHY3e4hPyaISQ8endeUo-vbn8uH672ry_ere-2KysbEWzAgV2sE7bvgXV6r5hDgc3gByRj4MFwWQHIIW2rgdpLbgReqFdK5xWQoA8JS8P3hrv24K5mOjz_vMwYVqyEbpTulpUX9EX_6DXaZmnms5I1nWN5kqrSr06UHZOOc84mu3sI8w7w5nZl2P25Zg_5VT4-Z1yGSK6e_RvGxXgB-DWB9z9R2Uu1pebg_Q3tTGeMQ</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Fennel, Zachary J.</creator><creator>Bourrant, Paul‐Emile</creator><creator>Kurian, Anu Susan</creator><creator>Petrocelli, Jonathan J.</creator><creator>Hart, Naomi M. 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P. ; Yee, Elena M. ; Boudina, Sihem ; Keirstead, Hans S. ; Nistor, Gabrielle ; Greilach, Scott A. ; Berchtold, Nicole C. ; Lane, Thomas E. ; Drummond, Micah J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3524-a8acbcd9c75a859740debdba3fe1fbca2036aa329cd7a3ccadfa729d52d9822a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adipocytes</topic><topic>adipogenesis</topic><topic>Adipose tissue</topic><topic>Adiposity - drug effects</topic><topic>Aging</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Body fat</topic><topic>Cell culture</topic><topic>Cell growth</topic><topic>Cell size</topic><topic>Collagen (type IV)</topic><topic>Culture media</topic><topic>Cytoskeleton</topic><topic>Energy expenditure</topic><topic>fibrosis</topic><topic>Immunomodulation</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Male</topic><topic>metabolic rate</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MicroRNAs</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Myotubes</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Phosphorylation</topic><topic>Physical activity</topic><topic>Quadriceps muscle</topic><topic>sarcopenia</topic><topic>Secretome</topic><topic>Secretome - metabolism</topic><topic>Skeletal muscle</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fennel, Zachary J.</creatorcontrib><creatorcontrib>Bourrant, Paul‐Emile</creatorcontrib><creatorcontrib>Kurian, Anu Susan</creatorcontrib><creatorcontrib>Petrocelli, Jonathan J.</creatorcontrib><creatorcontrib>Hart, Naomi M. 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M. P.</au><au>Yee, Elena M.</au><au>Boudina, Sihem</au><au>Keirstead, Hans S.</au><au>Nistor, Gabrielle</au><au>Greilach, Scott A.</au><au>Berchtold, Nicole C.</au><au>Lane, Thomas E.</au><au>Drummond, Micah J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stem cell secretome treatment improves whole‐body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2024-06</date><risdate>2024</risdate><volume>23</volume><issue>6</issue><spage>e14144</spage><epage>n/a</epage><pages>e14144-n/a</pages><issn>1474-9718</issn><issn>1474-9726</issn><eissn>1474-9726</eissn><abstract>Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22–24 months) compared to saline‐injected aged‐matched controls. Secretome delivery substantially increased whole‐body lean mass and decreased fat mass, corresponding to higher myofiber cross‐sectional area and smaller adipocyte size, respectively. Secretome‐treated mice also had greater whole‐body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome‐treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL‐6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome‐treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction. Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole‐body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice.
In this study, we show that the 4‐week administration of a stem cell secretome, made up of exosomes, growth, immune, and extracellular matrix factors, robustly ameliorated several hallmarks of aging in male mice resulting in improvements in physical function, metabolism, adiposity, and skeletal muscle remodeling.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>38500398</pmid><doi>10.1111/acel.14144</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-5961-8890</orcidid><orcidid>https://orcid.org/0000-0001-9482-7815</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes adipogenesis Adipose tissue Adiposity - drug effects Aging AKT protein Animals Body fat Cell culture Cell growth Cell size Collagen (type IV) Culture media Cytoskeleton Energy expenditure fibrosis Immunomodulation Kinases Lipids Male metabolic rate Mice Mice, Inbred C57BL MicroRNAs Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Myotubes NMR Nuclear magnetic resonance Phosphorylation Physical activity Quadriceps muscle sarcopenia Secretome Secretome - metabolism Skeletal muscle Stem cells Stem Cells - metabolism Vascular endothelial growth factor |
| title | Stem cell secretome treatment improves whole‐body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice |
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