Molecular responses in the telomere-mitochondrial axis of ageing in the elderly: a candidate gene approach
Pieters, Nicky × Janssens, Bram G Valeri, Linda Cox, Bianca Cuypers, Ann Dewitte, Harrie Plusquin, Michelle Smeets, Karen Nawrot, Tim #
Mechanisms of Ageing and Development vol:145 pages:51-57
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 -coactivator1
(PGC-1), peroxisome proliferator-activated receptor -coactivator1 (PGC-1), 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 telomeremitochondrial