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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/18897

Title: Molecular responses in the telomere-mitochondrial axis of ageing in the elderly: A candidate gene approach
Authors: PIETERS, Nicky
Janssen, Bram
Valeri, Linda
COX, Bianca
CUYPERS, Ann
Dewitte, Harrie
PLUSQUIN, Michelle
SMEETS, Karen
NAWROT, Tim
Issue Date: 2015
Publisher: ELSEVIER IRELAND LTD
Citation: MECHANISMS OF AGEING AND DEVELOPMENT, 145, p. 51-57
Abstract: Experimental evidence shows that telomere shortening induces mitochondrial damage but so far studies in humans are scarce. Here, we investigated the association between leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content in elderly and explored possible intermediate mechanisms by determining the gene expression profile of candidate genes in the telomere-mitochondrial axis of ageing. Among 166 non-smoking elderly, LTL, leukocyte mtDNA content and expression of candidate genes: sirtuin1 (SIRT1), tumor protein p53 (TP53), peroxisome proliferator-activated receptor gamma-coactivator1 alpha (PGC-1 alpha), peroxisome proliferator-activated receptor gamma-coactivator1 beta (PGC-1 beta), nuclear respiratory factor 1 (NRF1) and nuclear factor, erythroid 2 like 2 (NRF2), using a quantitave real time polymerase chain assay (qPCR). Statistical mediation analysis was used to study intermediate mechanisms of the telomere-mitochondrial axis of ageing. LTL correlated with leukocyte mtDNA content in our studied elderly (r = 0.23, p = 0.0047). SIRT1 gene expression correlated positively with LTL (r = 0.26, p = 0.0094) and leukocyte mtDNA content (r= 0.43, p<0.0001). The other studied candidates showed significant correlations in the telomere-mitochondrial interactome but not independent from SIRT1. SIRT1 gene expression was estimated to mediate 40% of the positive association between LTL and leukocyte mtDNA content. The key finding of our study was that SIRT1 expression plays a pivotal role in the telomere-mitochondrial interactome. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Notes: [Pieters, Nicky; Janssen, Bram G.; Cox, Bianca; Cuypers, Ann; Plusquin, Michelle; Smeets, Karen; Nawrot, Tim S.] Hasselt Univ, Ctr Environm Sci, B-3590 Diepenbeek, Belgium. [Valeri, Linda] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Dewitte, Harrie] Primary Hlth Care Ctr GVHV, Genk, Belgium. [Nawrot, Tim S.] Dept Publ Hlth Occupat & Environm Med, Leuven, Belgium.
URI: http://hdl.handle.net/1942/18897
DOI: 10.1016/j.mad.2015.02.003
ISI #: 000353732400006
ISSN: 0047-6374
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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