title: Telomere length and regulatory proteins in human skeletal muscle with and without ongoing regenerative cycles.
abstract: New insights suggest the existence of telomere regulatory mechanisms in several adult tissues. In this study, we aimed to assess in vivo telomere length and the presence of specific proteins involved in telomere regulation in a model of human skeletal muscle with (patients with dermatomyosis or polymyositis) and without ongoing regenerative events (healthy subjects). Mean (meanTRF) and minimal telomere (miniTRF) lengths and the expression of telomerase, tankyrase 1, TRF2 (telomeric repeat binding factor 2) and POT1 (protection of telomeres 1) were investigated in skeletal muscle samples from 12 patients (MYO) and 13 healthy subjects (CON). There was no significant shortening of telomeres in skeletal muscle from patients compared with control subjects (MYO, meanTRF length 11.0 ± 1.8 kbp and miniTRF length 4.7 ± 0.8 kbp; CON, meanTRF length 10.4 ± 1.1 kbp and miniTRF length 4.6 ± 0.5 kbp). Theoretically, telomere length can be controlled by endogenous mechanisms. Here, we show for the first time that expression levels of telomerase, tankyrase 1, TRF2 and POT1 were, respectively, six-, seven-, three- and fivefold higher in the nuclear fraction of skeletal muscle of MYO compared with CON (P < 0.05). This suggests the existence of endogenous mechanisms allowing for telomere regulation in skeletal muscle with ongoing cycles of degeneration and regeneration and a model where regulatory factors are possibly involved in the protection of skeletal muscle telomeres.
authors.affiliation: School of Health and Medical Sciences, University of Örebro, 70182 Örebro, Sweden.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ponsot
authors.forename: Andoni
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Delis
authors.forename: Fawzi
authors.initials: F
authors.lastname: Kadi
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D000089804:Shelterin Complex; D038501:Tankyrases / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000089804:Shelterin Complex; D038501:Tankyrases; D019098:Telomerase; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; C440849:POT1 protein, human; C504753:TERF2 protein, human; C418109:TNKS protein, human