Rapamycin slows aging in mice
Summary Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age‐dependent change, including alterations in heart, liver, adrenal g...
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| Veröffentlicht in: | Aging cell 2012-08, Vol.11 (4), p.675-682 |
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| creator | Wilkinson, John E. Burmeister, Lisa Brooks, Susan V. Chan, Chi‐Chao Friedline, Sabrina Harrison, David E. Hejtmancik, James F. Nadon, Nancy Strong, Randy Wood, Lauren K. Woodward, Maria A. Miller, Richard A. |
| description | Summary
Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age‐dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age‐dependent decline in spontaneous activity, occur more slowly in rapamycin‐treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue‐specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action. |
| doi_str_mv | 10.1111/j.1474-9726.2012.00832.x |
| format | Article |
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Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age‐dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age‐dependent decline in spontaneous activity, occur more slowly in rapamycin‐treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue‐specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/j.1474-9726.2012.00832.x</identifier><identifier>PMID: 22587563</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adrenal Gland Neoplasms - chemically induced ; Aging ; Aging - drug effects ; Aging - pathology ; Aging - physiology ; Animals ; Cataract - chemically induced ; Endometrium - drug effects ; Endometrium - pathology ; Female ; interventions ; Liver - drug effects ; Liver - pathology ; Longevity - drug effects ; Longevity - physiology ; longevity pathology ; Male ; Medical research ; Mice ; Mice, 129 Strain ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Motor Activity - drug effects ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - pathology ; Organ Specificity ; Rodents ; Sirolimus - blood ; Sirolimus - pharmacology ; Sirolimus - toxicity ; Tendons - drug effects ; Tendons - pathology ; Testis - drug effects ; Testis - pathology ; TOR ; TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><ispartof>Aging cell, 2012-08, Vol.11 (4), p.675-682</ispartof><rights>2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland</rights><rights>2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.</rights><rights>2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5682-1ee4b3cbd917b5478454ad5ffc6c2be5a4cd5a303897fe9631f92a7dde96bfc03</citedby><cites>FETCH-LOGICAL-c5682-1ee4b3cbd917b5478454ad5ffc6c2be5a4cd5a303897fe9631f92a7dde96bfc03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434687/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434687/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,729,782,786,887,1419,11569,27931,27932,45581,45582,46059,46483,53798,53800</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1474-9726.2012.00832.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22587563$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wilkinson, John E.</creatorcontrib><creatorcontrib>Burmeister, Lisa</creatorcontrib><creatorcontrib>Brooks, Susan V.</creatorcontrib><creatorcontrib>Chan, Chi‐Chao</creatorcontrib><creatorcontrib>Friedline, Sabrina</creatorcontrib><creatorcontrib>Harrison, David E.</creatorcontrib><creatorcontrib>Hejtmancik, James F.</creatorcontrib><creatorcontrib>Nadon, Nancy</creatorcontrib><creatorcontrib>Strong, Randy</creatorcontrib><creatorcontrib>Wood, Lauren K.</creatorcontrib><creatorcontrib>Woodward, Maria A.</creatorcontrib><creatorcontrib>Miller, Richard A.</creatorcontrib><title>Rapamycin slows aging in mice</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Summary
Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age‐dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age‐dependent decline in spontaneous activity, occur more slowly in rapamycin‐treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue‐specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action.</description><subject>Adrenal Gland Neoplasms - chemically induced</subject><subject>Aging</subject><subject>Aging - drug effects</subject><subject>Aging - pathology</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>Cataract - chemically induced</subject><subject>Endometrium - drug effects</subject><subject>Endometrium - pathology</subject><subject>Female</subject><subject>interventions</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Longevity - drug effects</subject><subject>Longevity - physiology</subject><subject>longevity pathology</subject><subject>Male</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, 129 Strain</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><subject>Motor Activity - drug effects</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Organ Specificity</subject><subject>Rodents</subject><subject>Sirolimus - blood</subject><subject>Sirolimus - pharmacology</subject><subject>Sirolimus - toxicity</subject><subject>Tendons - drug effects</subject><subject>Tendons - pathology</subject><subject>Testis - drug effects</subject><subject>Testis - pathology</subject><subject>TOR</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><issn>1474-9718</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkFtLw0AQhRdRbK3-BKXgc-Jes5sHhVLqBQqC6POw2WxqQi4129r237uxNeib8zJnmTNnhw-hMcEh8XVThIRLHsSSRiHFhIYYK0bD7REa9oPjXhM1QGfOFRgTGWN2igaUCiVFxIbo8kUvdbUzeT12ZbNxY73I68XYP6vc2HN0kunS2YtDH6G3-9nr9DGYPz88TSfzwIhI0YBYyxNmkjQmMhFcKi64TkWWmcjQxArNTSo0w0zFMrNxxEgWUy3T1OskM5iN0N0-d7lOKpsaW69aXcKyzSvd7qDROfyd1Pk7LJpPYJzxSEkfcH0IaJuPtXUrKJp1W_ubgQjOpcQEx96l9i7TNs61Nut_IBg6sFBAxww6ftCBhW-wsPWrV78v7Bd_SHrD7d6wyUu7-3cwTKazuVfsCznchrQ</recordid><startdate>201208</startdate><enddate>201208</enddate><creator>Wilkinson, John E.</creator><creator>Burmeister, Lisa</creator><creator>Brooks, Susan V.</creator><creator>Chan, Chi‐Chao</creator><creator>Friedline, Sabrina</creator><creator>Harrison, David E.</creator><creator>Hejtmancik, James F.</creator><creator>Nadon, Nancy</creator><creator>Strong, Randy</creator><creator>Wood, Lauren K.</creator><creator>Woodward, Maria A.</creator><creator>Miller, Richard A.</creator><general>Blackwell Publishing Ltd</general><general>John Wiley & Sons, Inc</general><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>7QP</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>201208</creationdate><title>Rapamycin slows aging in mice</title><author>Wilkinson, John E. ; Burmeister, Lisa ; Brooks, Susan V. ; Chan, Chi‐Chao ; Friedline, Sabrina ; Harrison, David E. ; Hejtmancik, James F. ; Nadon, Nancy ; Strong, Randy ; Wood, Lauren K. ; Woodward, Maria A. ; Miller, Richard A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5682-1ee4b3cbd917b5478454ad5ffc6c2be5a4cd5a303897fe9631f92a7dde96bfc03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adrenal Gland Neoplasms - chemically induced</topic><topic>Aging</topic><topic>Aging - drug effects</topic><topic>Aging - pathology</topic><topic>Aging - physiology</topic><topic>Animals</topic><topic>Cataract - chemically induced</topic><topic>Endometrium - drug effects</topic><topic>Endometrium - pathology</topic><topic>Female</topic><topic>interventions</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Longevity - drug effects</topic><topic>Longevity - physiology</topic><topic>longevity pathology</topic><topic>Male</topic><topic>Medical research</topic><topic>Mice</topic><topic>Mice, 129 Strain</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred DBA</topic><topic>Motor Activity - drug effects</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Organ Specificity</topic><topic>Rodents</topic><topic>Sirolimus - blood</topic><topic>Sirolimus - pharmacology</topic><topic>Sirolimus - toxicity</topic><topic>Tendons - drug effects</topic><topic>Tendons - pathology</topic><topic>Testis - drug effects</topic><topic>Testis - pathology</topic><topic>TOR</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wilkinson, John E.</creatorcontrib><creatorcontrib>Burmeister, Lisa</creatorcontrib><creatorcontrib>Brooks, Susan V.</creatorcontrib><creatorcontrib>Chan, Chi‐Chao</creatorcontrib><creatorcontrib>Friedline, Sabrina</creatorcontrib><creatorcontrib>Harrison, David E.</creatorcontrib><creatorcontrib>Hejtmancik, James F.</creatorcontrib><creatorcontrib>Nadon, Nancy</creatorcontrib><creatorcontrib>Strong, Randy</creatorcontrib><creatorcontrib>Wood, Lauren K.</creatorcontrib><creatorcontrib>Woodward, Maria A.</creatorcontrib><creatorcontrib>Miller, Richard A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Wilkinson, John E.</au><au>Burmeister, Lisa</au><au>Brooks, Susan V.</au><au>Chan, Chi‐Chao</au><au>Friedline, Sabrina</au><au>Harrison, David E.</au><au>Hejtmancik, James F.</au><au>Nadon, Nancy</au><au>Strong, Randy</au><au>Wood, Lauren K.</au><au>Woodward, Maria A.</au><au>Miller, Richard A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapamycin slows aging in mice</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2012-08</date><risdate>2012</risdate><volume>11</volume><issue>4</issue><spage>675</spage><epage>682</epage><pages>675-682</pages><issn>1474-9718</issn><eissn>1474-9726</eissn><abstract>Summary
Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age‐dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age‐dependent decline in spontaneous activity, occur more slowly in rapamycin‐treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue‐specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22587563</pmid><doi>10.1111/j.1474-9726.2012.00832.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Aging cell, 2012-08, Vol.11 (4), p.675-682 |
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| subjects | Adrenal Gland Neoplasms - chemically induced Aging Aging - drug effects Aging - pathology Aging - physiology Animals Cataract - chemically induced Endometrium - drug effects Endometrium - pathology Female interventions Liver - drug effects Liver - pathology Longevity - drug effects Longevity - physiology longevity pathology Male Medical research Mice Mice, 129 Strain Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred DBA Motor Activity - drug effects Myocytes, Cardiac - drug effects Myocytes, Cardiac - pathology Organ Specificity Rodents Sirolimus - blood Sirolimus - pharmacology Sirolimus - toxicity Tendons - drug effects Tendons - pathology Testis - drug effects Testis - pathology TOR TOR Serine-Threonine Kinases - antagonists & inhibitors |
| title | Rapamycin slows aging in mice |
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