title: Increased shelterin mRNA expression in peripheral blood mononuclear cells and skeletal muscle following an ultra-long-distance running event.
abstract: Located at the end of chromosomes, telomeres are progressively shortened with each replication of DNA during aging. Integral to the regulation of telomere length is a group of proteins making up the shelterin complex, whose tissue-specific function during physiological stress is not well understood. In this study, we examine the mRNA and protein levels of proteins within and associated with the shelterin complex in subjects (n = 8, mean age = 44 yr) who completed a physiological stress of seven marathons in 7 days. Twenty-two to 24 h after the last marathon, subjects had increased mRNA levels of DNA repair enzymes Ku70 and Ku80 (P < 0.05) in both skeletal muscle and peripheral blood mononuclear cells (PBMCs). Additionally, the PBMCs displayed an increment in three shelterin protein mRNA levels (TRF1, TRF2, and Pot-1, P < 0.05) following the event. Seven days of ultrarunning did not result in changes in mean telomere length, telomerase activity, hTert mRNA, or hterc mRNAs found in PBMCs. Higher protein concentrations of TRF2 were found in skeletal muscle vs. PBMCs at rest. Mean telomere length in skeletal muscle did not change and did not contain detectable levels of htert mRNA or telomerase activity. Furthermore, changes in the PBMCs could not be attributed to changes in the proportion of subtypes of CD4(+) or CD8(+) cells. We have provided the first evidence that, in humans, proteins within and associated with the shelterin complex increase at the mRNA level in response to a physiological stress differentially in PBMCs and skeletal muscle.
authors.affiliation: The Center of Inflammation and Metabolism, Department of Infectious Diseases and Copenhagen Muscle Research Center, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. mjlaye@gmail.com
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Laye
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Solomon
authors.forename: Kristian
authors.initials: K
authors.lastname: Karstoft
authors.forename: Karin K
authors.initials: KK
authors.lastname: Pedersen
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Nielsen
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D012420:Running / Q000502:physiology*; D000089804:Shelterin Complex; D013312:Stress, Physiological / Q000502:physiology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase; D045643:DNA Repair Enzymes