Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity

2.50
Hdl Handle:
http://hdl.handle.net/10547/594764
Title:
Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity
Authors:
Kim, Sangkyu; Bi, Xiuhua; Czarny-Ratajczak, Malwina ( 0000-0002-5601-7253 ) ; Dai, Jianliang; Welsh, David A.; Myers, Leann; Welsch, Michael A.; Cherry, Katie E; Arnold, Jonathan; Poon, Leonard W.; Jazwinski, S. Michal
Abstract:
Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age. We screened two genes known to be involved in telomere maintenance for association with the age-related decline in telomere length observed in our population to identify candidate longevity-associated genes. A single-nucleotide polymorphism located in the SIRT1 gene and another in the 3' flanking region of XRCC6 had significant effects on telomere length. At each bi-allelic locus, the minor variant was associated with longer telomeres, though the mode of inheritance fitting best differed between the two genes. No statistical interaction was detected for telomere length between the SIRT1 and XRCC6 variants or between these polymorphisms and age. The SIRT1 locus was significantly associated with longevity (P < 0.003). The frequency of the minor allele was higher in long-lived cases than in young controls, which coincides with the protective role of the minor variant for telomere length. In contrast, the XRCC6 variant was not associated with longevity. Furthermore, it did not affect the association of SIRT1 with exceptional survival. The association of the same variant of SIRT1 with longevity was near significant (P < 0.07) in a second population. These results suggest a potential role of SIRT1 in linking telomere length and longevity. Given the differences between this gene and XRCC6, they point to the distinct impact that alternate pathways of telomere maintenance may have on aging and exceptional survival.
Affiliation:
Tulane University Health Sciences Center
Citation:
Kim, S. et al (2012) 'Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity'. Biogerontology 13 (2):119-31
Publisher:
Springer
Journal:
Biogerontology
Issue Date:
Apr-2012
URI:
http://hdl.handle.net/10547/594764
DOI:
10.1007/s10522-011-9360-5
PubMed ID:
21972126
PubMed Central ID:
PMC3272146
Additional Links:
http://link.springer.com/article/10.1007/s10522-011-9360-5; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272146/
Type:
Article
Language:
en
ISSN:
1573-6768
Appears in Collections:
Muscle Cellular and Molecular Physiology

Full metadata record

DC FieldValue Language
dc.contributor.authorKim, Sangkyuen
dc.contributor.authorBi, Xiuhuaen
dc.contributor.authorCzarny-Ratajczak, Malwinaen
dc.contributor.authorDai, Jianliangen
dc.contributor.authorWelsh, David A.en
dc.contributor.authorMyers, Leannen
dc.contributor.authorWelsch, Michael A.en
dc.contributor.authorCherry, Katie Een
dc.contributor.authorArnold, Jonathanen
dc.contributor.authorPoon, Leonard W.en
dc.contributor.authorJazwinski, S. Michalen
dc.date.accessioned2016-01-25T10:41:51Zen
dc.date.available2016-01-25T10:41:51Zen
dc.date.issued2012-04en
dc.identifier.citationKim, S. et al (2012) 'Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity'. Biogerontology 13 (2):119-31en
dc.identifier.issn1573-6768en
dc.identifier.pmid21972126en
dc.identifier.doi10.1007/s10522-011-9360-5en
dc.identifier.urihttp://hdl.handle.net/10547/594764en
dc.description.abstractLeukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age. We screened two genes known to be involved in telomere maintenance for association with the age-related decline in telomere length observed in our population to identify candidate longevity-associated genes. A single-nucleotide polymorphism located in the SIRT1 gene and another in the 3' flanking region of XRCC6 had significant effects on telomere length. At each bi-allelic locus, the minor variant was associated with longer telomeres, though the mode of inheritance fitting best differed between the two genes. No statistical interaction was detected for telomere length between the SIRT1 and XRCC6 variants or between these polymorphisms and age. The SIRT1 locus was significantly associated with longevity (P < 0.003). The frequency of the minor allele was higher in long-lived cases than in young controls, which coincides with the protective role of the minor variant for telomere length. In contrast, the XRCC6 variant was not associated with longevity. Furthermore, it did not affect the association of SIRT1 with exceptional survival. The association of the same variant of SIRT1 with longevity was near significant (P < 0.07) in a second population. These results suggest a potential role of SIRT1 in linking telomere length and longevity. Given the differences between this gene and XRCC6, they point to the distinct impact that alternate pathways of telomere maintenance may have on aging and exceptional survival.en
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urlhttp://link.springer.com/article/10.1007/s10522-011-9360-5en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272146/en
dc.rightsArchived with thanks to Biogerontologyen
dc.subjecttelomeresen
dc.subjectageen
dc.subjectageingen
dc.subject.mesh3' Flanking Regionen
dc.subject.meshAdulten
dc.subject.meshAge Factorsen
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshAntigens, Nuclearen
dc.subject.meshCase-Control Studiesen
dc.subject.meshDNA-Binding Proteinsen
dc.subject.meshFemaleen
dc.subject.meshGene Frequencyen
dc.subject.meshGenotypeen
dc.subject.meshGeorgiaen
dc.subject.meshHumansen
dc.subject.meshLod Scoreen
dc.subject.meshLongevityen
dc.subject.meshLouisianaen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMultivariate Analysisen
dc.subject.meshOdds Ratioen
dc.subject.meshPhenotypeen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshProportional Hazards Modelsen
dc.subject.meshSirtuin 1en
dc.subject.meshSurvival Analysisen
dc.subject.meshTelomereen
dc.subject.meshTelomere Shorteningen
dc.subject.meshYoung Adulten
dc.titleTelomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevityen
dc.typeArticleen
dc.contributor.departmentTulane University Health Sciences Centeren
dc.identifier.journalBiogerontologyen
dc.identifier.pmcidPMC3272146en

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