Long-lived Indy and calorie restriction interact to extend life span
Calorie restriction (CR) improves health and extends life span in a variety of species. Despite many downstream molecules and physiological systems having been identified as being regulated by CR, the mechanism by which CR extends life span remains unclear. The Drosophila gene Indy (for I'm not...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2009-06, Vol.106 (23), p.9262-9267 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Wang, Pei-Yu Neretti, Nicola Whitaker, Rachel Hosier, Suzanne Chang, Chengyi Lu, Daniel Rogina, Blanka Helfand, Stephen L |
| description | Calorie restriction (CR) improves health and extends life span in a variety of species. Despite many downstream molecules and physiological systems having been identified as being regulated by CR, the mechanism by which CR extends life span remains unclear. The Drosophila gene Indy (for I'm not dead yet), involved in the transport and storage of Krebs cycle intermediates in tissues important in fly metabolism, was proposed to regulate life span via an effect on metabolism that could overlap with CR. In this study, we report that CR down regulates Indy mRNA expression, and that CR and the level of Indy expression interact to affect longevity. Optimal life span extension is seen when Indy expression is decreased between 25 and 75% of normal. Indy long-lived flies show several phenotypes that are shared by long-lived CR flies, including decreased insulin-like signaling, lipid storage, weight gain, and resistance to starvation as well as an increase in spontaneous physical activity. We conclude that Indy and CR interact to affect longevity and that a decrease in Indy may induce a CR-like status that confers life span extension. |
| doi_str_mv | 10.1073/pnas.0904115106 |
| format | Article |
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Despite many downstream molecules and physiological systems having been identified as being regulated by CR, the mechanism by which CR extends life span remains unclear. The Drosophila gene Indy (for I'm not dead yet), involved in the transport and storage of Krebs cycle intermediates in tissues important in fly metabolism, was proposed to regulate life span via an effect on metabolism that could overlap with CR. In this study, we report that CR down regulates Indy mRNA expression, and that CR and the level of Indy expression interact to affect longevity. Optimal life span extension is seen when Indy expression is decreased between 25 and 75% of normal. Indy long-lived flies show several phenotypes that are shared by long-lived CR flies, including decreased insulin-like signaling, lipid storage, weight gain, and resistance to starvation as well as an increase in spontaneous physical activity. We conclude that Indy and CR interact to affect longevity and that a decrease in Indy may induce a CR-like status that confers life span extension.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0904115106</identifier><identifier>PMID: 19470468</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Aging - genetics ; Animals ; Biological Sciences ; Caloric Restriction ; Calories ; Dicarboxylic Acid Transporters - genetics ; Dicarboxylic Acid Transporters - metabolism ; Drosophila ; Drosophila melanogaster ; Drosophila melanogaster - physiology ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; Female ; Food ; food deprivation ; Food intake ; Gene expression ; Gene Expression Regulation ; genes ; Indy gene ; insect genetics ; Insects ; Insulin ; Life Expectancy ; Life span ; Lipid Metabolism ; Lipids ; lipogenesis ; Longevity ; low calorie diet ; Male ; Messenger RNA ; Metabolism ; Molecules ; physical activity ; Ribonucleic acid ; RNA ; Signal transduction ; Starvation ; Studies ; Symporters - genetics ; Symporters - metabolism ; triacylglycerols</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2009-06, Vol.106 (23), p.9262-9267</ispartof><rights>Copyright National Academy of Sciences Jun 9, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-15055dc3019aa64b2c5ec902a72904de2ce7c170e6549db6637e6a030ad1e75f3</citedby><cites>FETCH-LOGICAL-c587t-15055dc3019aa64b2c5ec902a72904de2ce7c170e6549db6637e6a030ad1e75f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/106/23.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40483203$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40483203$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19470468$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Pei-Yu</creatorcontrib><creatorcontrib>Neretti, Nicola</creatorcontrib><creatorcontrib>Whitaker, Rachel</creatorcontrib><creatorcontrib>Hosier, Suzanne</creatorcontrib><creatorcontrib>Chang, Chengyi</creatorcontrib><creatorcontrib>Lu, Daniel</creatorcontrib><creatorcontrib>Rogina, Blanka</creatorcontrib><creatorcontrib>Helfand, Stephen L</creatorcontrib><title>Long-lived Indy and calorie restriction interact to extend life span</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Calorie restriction (CR) improves health and extends life span in a variety of species. Despite many downstream molecules and physiological systems having been identified as being regulated by CR, the mechanism by which CR extends life span remains unclear. The Drosophila gene Indy (for I'm not dead yet), involved in the transport and storage of Krebs cycle intermediates in tissues important in fly metabolism, was proposed to regulate life span via an effect on metabolism that could overlap with CR. In this study, we report that CR down regulates Indy mRNA expression, and that CR and the level of Indy expression interact to affect longevity. Optimal life span extension is seen when Indy expression is decreased between 25 and 75% of normal. Indy long-lived flies show several phenotypes that are shared by long-lived CR flies, including decreased insulin-like signaling, lipid storage, weight gain, and resistance to starvation as well as an increase in spontaneous physical activity. We conclude that Indy and CR interact to affect longevity and that a decrease in Indy may induce a CR-like status that confers life span extension.</description><subject>Aging - genetics</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Caloric Restriction</subject><subject>Calories</subject><subject>Dicarboxylic Acid Transporters - genetics</subject><subject>Dicarboxylic Acid Transporters - metabolism</subject><subject>Drosophila</subject><subject>Drosophila melanogaster</subject><subject>Drosophila melanogaster - physiology</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Female</subject><subject>Food</subject><subject>food deprivation</subject><subject>Food intake</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>genes</subject><subject>Indy gene</subject><subject>insect genetics</subject><subject>Insects</subject><subject>Insulin</subject><subject>Life Expectancy</subject><subject>Life span</subject><subject>Lipid Metabolism</subject><subject>Lipids</subject><subject>lipogenesis</subject><subject>Longevity</subject><subject>low calorie diet</subject><subject>Male</subject><subject>Messenger RNA</subject><subject>Metabolism</subject><subject>Molecules</subject><subject>physical activity</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signal transduction</subject><subject>Starvation</subject><subject>Studies</subject><subject>Symporters - genetics</subject><subject>Symporters - metabolism</subject><subject>triacylglycerols</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1vEzEQhi0EoqFw5gSsOCAu246_dy9IqHxVisQBerYc72xwtLGD7a3ov8dRogY4cPJhnnnHj15CnlO4oKD55S7YfAE9CEolBfWALCj0tFWih4dkAcB02wkmzsiTnDcA0MsOHpMz2gsNQnUL8mEZw7qd_C0OzXUY7hobhsbZKSaPTcJcknfFx9D4UDBZV5oSG_xVsGKTH7HJOxuekkejnTI-O77n5ObTx-9XX9rl18_XV--XrZOdLi2VIOXgONDeWiVWzEl0PTCrWTUYkDnUjmpAJUU_rJTiGpUFDnagqOXIz8m7Q-5uXm1xcBhKspPZJb-16c5E683fk-B_mHW8NUx1UgtRA94cA1L8OVc7s_XZ4TTZgHHORmleT0tawdf_gJs4p1DlDAPKBQMmK3R5gFyKOScc739CwezrMft6zKmeuvHyT4ETf-yjAq-OwH7zFKcM46ZnilXi7f8JM87TVGpFFX1xQDe5xHTPChAdZ8BPx0YbjV0nn83Nt70eULU3ZPw3ste2IA</recordid><startdate>20090609</startdate><enddate>20090609</enddate><creator>Wang, Pei-Yu</creator><creator>Neretti, Nicola</creator><creator>Whitaker, Rachel</creator><creator>Hosier, Suzanne</creator><creator>Chang, Chengyi</creator><creator>Lu, Daniel</creator><creator>Rogina, Blanka</creator><creator>Helfand, Stephen L</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090609</creationdate><title>Long-lived Indy and calorie restriction interact to extend life span</title><author>Wang, Pei-Yu ; 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Despite many downstream molecules and physiological systems having been identified as being regulated by CR, the mechanism by which CR extends life span remains unclear. The Drosophila gene Indy (for I'm not dead yet), involved in the transport and storage of Krebs cycle intermediates in tissues important in fly metabolism, was proposed to regulate life span via an effect on metabolism that could overlap with CR. In this study, we report that CR down regulates Indy mRNA expression, and that CR and the level of Indy expression interact to affect longevity. Optimal life span extension is seen when Indy expression is decreased between 25 and 75% of normal. Indy long-lived flies show several phenotypes that are shared by long-lived CR flies, including decreased insulin-like signaling, lipid storage, weight gain, and resistance to starvation as well as an increase in spontaneous physical activity. We conclude that Indy and CR interact to affect longevity and that a decrease in Indy may induce a CR-like status that confers life span extension.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>19470468</pmid><doi>10.1073/pnas.0904115106</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Aging - genetics Animals Biological Sciences Caloric Restriction Calories Dicarboxylic Acid Transporters - genetics Dicarboxylic Acid Transporters - metabolism Drosophila Drosophila melanogaster Drosophila melanogaster - physiology Drosophila Proteins - genetics Drosophila Proteins - metabolism Female Food food deprivation Food intake Gene expression Gene Expression Regulation genes Indy gene insect genetics Insects Insulin Life Expectancy Life span Lipid Metabolism Lipids lipogenesis Longevity low calorie diet Male Messenger RNA Metabolism Molecules physical activity Ribonucleic acid RNA Signal transduction Starvation Studies Symporters - genetics Symporters - metabolism triacylglycerols |
| title | Long-lived Indy and calorie restriction interact to extend life span |
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