Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription.
DNA breaks activate the DNA damage response and, if left unrepaired, trigger cellular senescence. Telomeres are specialized nucleoprotein structures that protect chromosome ends from persistent DNA damage response activation. Whether protection can be enhanced to counteract the age-dependent decline in telomere integrity is a challenging question. Telomeric repeat-containing RNA (TERRA), which is transcribed from telomeres, emerged as important player in telomere integrity. However, how human telomere transcription is regulated is still largely unknown. We identify nuclear respiratory factor 1 and peroxisome proliferator-activated receptor γ coactivator 1α as regulators of human telomere transcription. In agreement with an upstream regulation of these factors by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), pharmacological activation of AMPK in cancer cell lines or in normal nonproliferating myotubes up-regulated TERRA, thereby linking metabolism to telomere fitness. Cycling endurance exercise, which is associated with AMPK activation, increased TERRA levels in skeletal muscle biopsies obtained from 10 healthy young volunteers. The data support the idea that exercise may protect against aging.
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.
Aurélie
A
Diman
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.
Joanna
J
Boros
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.
Florian
F
Poulain
Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin 1, 1348 Louvain-la-Neuve, Belgium.
Julie
J
Rodriguez
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.; Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin 1, 1348 Louvain-la-Neuve, Belgium.
Marin
M
Purnelle
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.
Harikleia
H
Episkopou
Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 55, 1200 Brussels, Belgium.
Luc
0000-0003-0655-7099
L
Bertrand
Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin 1, 1348 Louvain-la-Neuve, Belgium.
Marc
0000-0001-8182-1588
M
Francaux
Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin 1, 1348 Louvain-la-Neuve, Belgium.
Louise
L
Deldicque
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.
Anabelle
A
Decottignies
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015444:Exercise; D017930:Genes, Reporter; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000737:chemistry / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D011485:Protein Binding; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D055815:Young Adult
D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D055372:AMP-Activated Protein Kinases
AMPK; NRF1; TERRA; Telomere; exercise