Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile
Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/i...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2015
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| Online Access: | http://hdl.handle.net/1721.1/96746 https://orcid.org/0000-0002-0079-4467 https://orcid.org/0000-0002-1446-7256 |
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| author | Mercken, Evi M. Crosby, Seth D. Lamming, Dudley W. JeBailey, Lellean Krzysik-Walker, Susan Villareal, Dennis T. Capri, Miriam Franceschi, Claudio Zhang, Yongqing Becker, Kevin de Cabo, Rafael Fontana, Luigi Sabatini, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Mercken, Evi M. Crosby, Seth D. Lamming, Dudley W. JeBailey, Lellean Krzysik-Walker, Susan Villareal, Dennis T. Capri, Miriam Franceschi, Claudio Zhang, Yongqing Becker, Kevin de Cabo, Rafael Fontana, Luigi Sabatini, David |
| author_sort | Mercken, Evi M. |
| collection | MIT |
| description | Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans, CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis, and inflammation. Furthermore, our data identify promising pathways for therapeutic targets to combat age-related diseases and promote health in humans. |
| first_indexed | 2024-09-23T13:54:52Z |
| format | Article |
| id | mit-1721.1/96746 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:54:52Z |
| publishDate | 2015 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/967462022-09-28T17:01:39Z Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile Mercken, Evi M. Crosby, Seth D. Lamming, Dudley W. JeBailey, Lellean Krzysik-Walker, Susan Villareal, Dennis T. Capri, Miriam Franceschi, Claudio Zhang, Yongqing Becker, Kevin de Cabo, Rafael Fontana, Luigi Sabatini, David Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Lamming, Dudley W. Sabatini, David M. Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans, CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis, and inflammation. Furthermore, our data identify promising pathways for therapeutic targets to combat age-related diseases and promote health in humans. American Federation for Aging Research National Center for Research Resources (U.S.) (Grant UL1 RR024992) National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant P30DK056341) 2015-04-23T17:39:19Z 2015-04-23T17:39:19Z 2013-06 2013-04 Article http://purl.org/eprint/type/JournalArticle 14749718 1474-9728 http://hdl.handle.net/1721.1/96746 Mercken, Evi M., Seth D. Crosby, Dudley W. Lamming, Lellean JeBailey, Susan Krzysik-Walker, Dennis T. Villareal, Miriam Capri, et al. “Calorie Restriction in Humans Inhibits the PI3K/AKT Pathway and Induces a Younger Transcription Profile.” Aging Cell 12, no. 4 (June 5, 2013): 645–651. © 2013 John Wiley & Sons Ltd and the Anatomical Society https://orcid.org/0000-0002-0079-4467 https://orcid.org/0000-0002-1446-7256 en_US http://dx.doi.org/10.1111/acel.12088 Aging Cell Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Wiley Blackwell Wiley |
| spellingShingle | Mercken, Evi M. Crosby, Seth D. Lamming, Dudley W. JeBailey, Lellean Krzysik-Walker, Susan Villareal, Dennis T. Capri, Miriam Franceschi, Claudio Zhang, Yongqing Becker, Kevin de Cabo, Rafael Fontana, Luigi Sabatini, David Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile |
| title | Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile |
| title_full | Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile |
| title_fullStr | Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile |
| title_full_unstemmed | Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile |
| title_short | Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile |
| title_sort | calorie restriction in humans inhibits the pi3k akt pathway and induces a younger transcription profile |
| url | http://hdl.handle.net/1721.1/96746 https://orcid.org/0000-0002-0079-4467 https://orcid.org/0000-0002-1446-7256 |
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