| HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging. | |
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MedLine Citation:
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PMID: 20569235 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity. |
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Authors:
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S Michal Jazwinski; Sangkyu Kim; Jianliang Dai; Li Li; Xiuhua Bi; James C Jiang; Jonathan Arnold; Mark A Batzer; Jerilyn A Walker; David A Welsh; Christina M Lefante; Julia Volaufova; Leann Myers; L Joseph Su; Dorothy B Hausman; Michael V Miceli; Eric Ravussin; Leonard W Poon; Katie E Cherry; Michael A Welsch; |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-04 |
Journal Detail:
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Title: Aging cell Volume: 9 ISSN: 1474-9726 ISO Abbreviation: Aging Cell Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-17 Completed Date: 2011-02-04 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: England |
Other Details:
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Languages: eng Pagination: 698-708 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
Affiliation:
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Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. sjazwins@tulane.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Aged, 80 and over Aging / genetics* Apolipoproteins E / genetics* Female Follow-Up Studies Genetic Variation / genetics Haplotypes Humans Longevity / genetics* Male Membrane Proteins / genetics* Middle Aged Proto-Oncogene Proteins p21(ras) / genetics* Sphingosine N-Acyltransferase |
| Grant Support | |
ID/Acronym/Agency:
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P01 AG017553/AG/NIA NIH HHS; P01 AG022064/AG/NIA NIH HHS; P01 AG022064-06S1/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Membrane Proteins; EC 2.3.1.24/CERS1 protein, human; EC 2.3.1.24/Sphingosine N-Acyltransferase; EC 3.6.5.2/HRAS protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
| Investigator | |
Investigator/Affiliation:
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R C Green / ; M Gearing / ; W R Markesbery / ; J L Woodard / ; M A Johnson / ; J S Tenover / ; I C Siegler / ; P Martin / ; M MacDonald / ; C Rott / ; W L Rodgers / ; A Davey / ; M Allen / ; I E Antikainen / ; A M Arce / ; J Arceneaux / ; E O Boudreaux / ; L Byerley / ; P A Callinan / ; C M Champagne / ; H Cheng / ; Y-w Chiu / ; L Cosenza / ; M E Cress / ; M Czarny-Ratajczak / ; J P DeLany / ; J Denver / ; A Deutsch / ; M J deVeer / ; D A Dobrosielski / ; R Ellis / ; A Ermolao / ; M Erwin / ; M Erwin / ; J Fabre / ; E Fontham / ; M Frisard / ; P Geiselman / ; L Goodwin / ; V Greco / ; S Hadie / ; T Hall / ; M Hamilton / ; S W Herke / ; K Hawley / ; J Hayden / ; K Hebert / ; F Holton / ; H-C Hsu / ; D Johannsen / ; L Kawasaki / ; B Kimball / ; C King-Rowley / ; M Konkel / ; R Kuhn / ; K Landry / ; C Lavie / ; D LaVie / ; M Leblanc / ; H-Y Lin / ; K Lopez / ; B McEvoy-Hein / ; J D Mountz / ; E Olinde / ; J Owens / ; K Pedersen / ; A Pellett / ; P Remedios / ; Y Robertson / ; J Rood / ; H Rothschild / ; R A Russell / ; E Sandifer / ; B Schmidt / ; R Schwartz / ; D K Scott / ; J Silva / ; F N Standberry / ; J Thomson / ; A Tiwari / ; V Toups / ; C Traylor / ; C Velasco-Gonzalez / ; C Waguespack / ; X-Y Wang / ; R H Wood / ; Q Yu / ; S Zehr / ; P Zhang / |
| Comments/Corrections | |
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