Molecular responses in the telomere-mitochondrial axis of ageing in the elderly: a candidate gene approach.
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 γ-coactivator1α (PGC-1α), peroxisome proliferator-activated receptor γ-coactivator1β (PGC-1β), 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.
Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D Diepenbeek, Belgium.
Nicky
N
Pieters
Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D Diepenbeek, Belgium.
Bram G
BG
Janssen
Department of Biostatistics, School of Public Health, Harvard University, 655 Huntington Avenue, Boston, MA, USA.
Linda
L
Valeri
Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D Diepenbeek, Belgium.
Bianca
B
Cox
Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D Diepenbeek, Belgium.
Ann
A
Cuypers
Primary Health Care Centre GVHV, Keinkesstraat 3a, Genk, Belgium.
Harrie
H
Dewitte
Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D Diepenbeek, Belgium.
Michelle
M
Plusquin
Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D Diepenbeek, Belgium.
Karen
K
Smeets
Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D Diepenbeek, Belgium; Department of Public Health, Occupational & Environmental Medicine, Herestraat 49, Leuven, Belgium. Electronic address: tim.nawrot@uhasselt.be.
Tim S
TS
Nawrot
D000368:Aged; D000375:Aging / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis
D004272:DNA, Mitochondrial
Ageing; Mitochondrial DNA content; Targeted transcriptomics; Telomere length