Can lifelong endurance exercise improve ageing through beneficial effects on circadian timing function, muscular performance and health status in men? Protocol for a comparative cross-sectional study


https://doi.org/10.4081/ejtm.2023.12012
Vol. 33 No. 4 (2023)
Submitted: 26 October 2023
Accepted: 21 November 2023
Published: 5 December 2023
Circadian, aging, exercise, sports medicine, molecular biology, sleep/wake rhythm
Abstract Views: 2035
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Authors

  • Genc Berisha
    genc.berisha@uniba.sk
    Comenius University in Bratislava, Faculty of Physical Education and Sport, Department of Biological and Medical Sciences, Slovakia. https://orcid.org/0000-0002-1171-1583
  • Milan Sedliak Comenius University in Bratislava, Faculty of Physical Education and Sport, Department of Biological and Medical Sciences, Slovakia.
  • Michal Zeman Comenius University in Bratislava, Faculty of Natural Sciences, Department of Animal Physiology and Ethology, Slovakia.
  • Dušan Hamar Comenius University in Bratislava, Faculty of Physical Education and Sport, Department of Biological and Medical Sciences, Slovakia.
  • Ján Cvečka Comenius University in Bratislava, Faculty of Physical Education and Sport, Professor Hamar Diagnostic Centre, Slovakia.
  • Veronika Tirpáková Comenius University in Bratislava, Faculty of Physical Education and Sport, Professor Hamar Diagnostic Centre, Slovakia.
  • Matej Vajda Comenius University in Bratislava, Faculty of Physical Education and Sport, Professor Hamar Diagnostic Centre, Slovakia.
  • Ľudmila Oreská Comenius University in Bratislava, Faculty of Physical Education and Sport, Department of Biological and Medical Sciences, Slovakia.
  • Alena Černáčková Comenius University in Bratislava, Faculty of Physical Education and Sport, Department of Biological and Medical Sciences, Slovakia.
  • Martin Čupka Comenius University in Bratislava, Faculty of Physical Education and Sport, Department of Biological and Medical Sciences, Slovakia.
  • Nejc Šarabon University of Primorska, Faculty of Health Sciences, Slovenia.
  • Feliciano Protasi Gabriele d'Annunzio University of Chieti and Pescara, Center for Advanced Studies and Technology, Department of Medicine and Aging Sciences, Italy.
  • Sandra Zampieri University of Padova, Department of Surgery, Oncology and Gastroenterology, Department of Biomedical Sciences, Italy.
  • Helmut Kern Ludwig Boltzmann Institute for Rehabilitation Research, St. Pölten, Austria and 2. Physiko- und Rheumatherapie, Austria.
  • Stefan Lofler Ludwig Boltzmann Institute for Rehabilitation Research, St. Pölten, Austria and 2. Physiko- und Rheumatherapie, Austria.
  • Antonio Musaro University of Rome La Sapienza, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Scuola Superiore di Studi Avanzati Sapienza, Italy.
  • Katarína Stebelová Comenius University in Bratislava, Faculty of Natural Sciences, Department of Animal Physiology and Ethology, Slovakia.
  • Monika Okuliarová Comenius University in Bratislava, Faculty of Natural Sciences, Department of Animal Physiology and Ethology, Slovakia.

A well-synchronized circadian system is a manifestation of an individual's health. A gradual weakening of the circadian timing function characterizes aging. Regular exercise has been suggested as a modality to improve many detrimental changes associated with aging. Therefore, we aim to examine the benefits and risks of lifelong endurance exercise on age-dependent changes in the circadian time-keeping function, the performance of the muscular system and health status. The study protocol has a comparative cross-sectional design, including groups of senior (65 to 75 years old, n=16) and young (20-30 years old, n=16) endurance runners and triathletes. Age-matched groups of young and elderly sedentary men are included as controls. The circadian function is evaluated mainly by measurement of urinary 6-sulphatoxymelatonin, a metabolite of the hormone melatonin shown to participate in the modulation of sleep cycles. The 6-sulphatoxymelatonin will be assessed in urine samples collected upon awakening in the morning and in the late evening, as a marker of melatonin production. In addition, sleep/activity rhythms and sleep quality will be measured by wrist actigraphy. Performance of the muscular system will be assessed by examination of muscular strength and quantifying of gene expression in the skeletal muscle tissue samples. Health status and age-induced reduction in immune function are to be analysed via the balance of pro- and anti-inflammatory immune markers in the plasma and skeletal muscle, body composition, bone density and physical fitness.


Giacomoni M, Edwards B, Bambaeichi E. Gender differences in the circadian variations in muscle strength assessed with and without superimposed electrical twitches. Ergonomics. 2005 Sep 15-Nov 15;48(11-14):1473-87. PMID: 16338714. DOI: https://doi.org/10.1080/00140130500101452

Küüsmaa M, Sedliak M, Häkkinen K. Effects of time-of-day on neuromuscular function in untrained men: Specific responses of high morning performers and high evening performers. Chronobiol Int. 2015;32(8):1115-24. Epub 2015 Sep 11. PMID: 26361893. DOI: https://doi.org/10.3109/07420528.2015.1065269

Mora-Rodríguez R, García Pallarés J, López-Samanes Á, Ortega JF, Fernández-Elías VE. Caffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained men. PLoS One. 2012;7(4):e33807. Epub 2012 Apr 4. PMID: 22496767; PMCID: PMC3319538. DOI: https://doi.org/10.1371/journal.pone.0033807

Sedliak M, Finni T, Cheng S, Haikarainen T, Häkkinen K. Diurnal variation in maximal and submaximal strength, power and neural activation of leg extensors in men: multiple sampling across two consecutive days. Int J Sports Med. 2008 Mar;29(3):217-24. Epub 2007 Jul 5. PMID: 17614012. DOI: https://doi.org/10.1055/s-2007-965125

Amaro-Gahete FJ, Jurado-Fasoli L, Triviño AR, Sanchez-Delgado G, De-la-O A, Helge JW, Ruiz JR. Diurnal Variation of Maximal Fat-Oxidation Rate in Trained Male Athletes. Int J Sports Physiol Perform. 2019 Sep 1;14(8):1140-1146. PMID: 30702364. DOI: https://doi.org/10.1123/ijspp.2018-0854

Basti A, Yalçin M, Herms D, Hesse J, Aboumanify O, Li Y, Aretz Z, Garmshausen J, El-Athman R, Hastermann M, Blottner D, Relógio A. Diurnal variations in the expression of core-clock genes correlate with resting muscle properties and predict fluctuations in exercise performance across the day. BMJ Open Sport Exerc Med. 2021 Feb 10;7(1):e000876. PMID: 33680499; PMCID: PMC7878143. DOI: https://doi.org/10.1136/bmjsem-2020-000876

Dyar KA, Ciciliot S, Wright LE, Biensø RS, Tagliazucchi GM, Patel VR, Forcato M, Paz MI, Gudiksen A, Solagna F, Albiero M, Moretti I, Eckel-Mahan KL, Baldi P, Sassone-Corsi P, Rizzuto R, Bicciato S, Pilegaard H, Blaauw B, Schiaffino S. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock. Mol Metab. 2013 Oct 23;3(1):29-41. Erratum in: Mol Metab. 2014 Dec;3(9):857. PMID: 24567902; PMCID: PMC3929910. DOI: https://doi.org/10.1016/j.molmet.2014.09.002

Perrin L, Loizides-Mangold U, Skarupelova S, Pulimeno P, Chanon S, Robert M, Bouzakri K, Modoux C, Roux-Lombard P, Vidal H, Lefai E, Dibner C. Human skeletal myotubes display a cell-autonomous circadian clock implicated in basal myokine secretion. Mol Metab. 2015 Aug 6;4(11):834-45. PMID: 26629407; PMCID: PMC4632112. DOI: https://doi.org/10.1016/j.molmet.2015.07.009

van Moorsel D, Hansen J, Havekes B, Scheer FAJL, Jörgensen JA, Hoeks J, Schrauwen-Hinderling VB, Duez H, Lefebvre P, Schaper NC, Hesselink MKC, Staels B, Schrauwen P. Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity. Mol Metab. 2016 Jul 1;5(8):635-645. PMID: 27656401; PMCID: PMC5021670. DOI: https://doi.org/10.1016/j.molmet.2016.06.012

Perrin L, Loizides-Mangold U, Chanon S, Gobet C, Hulo N, Isenegger L, Weger BD, Migliavacca E, Charpagne A, Betts JA, Walhin JP, Templeman I, Stokes K, Thompson D, Tsintzas K, Robert M, Howald C, Riezman H, Feige JN, Karagounis LG, Johnston JD, Dermitzakis ET, Gachon F, Lefai E, Dibner C. Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle. Elife. 2018 Apr 16;7:e34114. PMID: 29658882; PMCID: PMC5902165. DOI: https://doi.org/10.7554/eLife.34114

Sedliak M, Finni T, Cheng S, Kraemer WJ, Häkkinen K. Effect of time-of-day-specific strength training on serum hormone concentrations and isometric strength in men. Chronobiol Int. 2007;24(6):1159-77. PMID: 18075805. DOI: https://doi.org/10.1080/07420520701800686

Sedliak M, Finni T, Cheng S, Lind M, Häkkinen K. Effect of time-of-day-specific strength training on muscular hypertrophy in men. J Strength Cond Res. 2009 Dec;23(9):2451-7. PMID: 19910830. DOI: https://doi.org/10.1519/JSC.0b013e3181bb7388

Sedliak M, Zeman M, Buzgó G, Cvecka J, Hamar D, Laczo E, Okuliarova M, Vanderka M, Kampmiller T, Häkkinen K, Ahtiainen JP, Hulmi JJ, Nilsen TS, Wiig H, Raastad T. Morphological, molecular and hormonal adaptations to early morning versus afternoon resistance training. Chronobiol Int. 2018 Apr;35(4):450-464. Epub 2017 Dec 28. PMID: 29283292. DOI: https://doi.org/10.1080/07420528.2017.1411360

Mirizio GG, Nunes RSM, Vargas DA, Foster C, Vieira E. Time-of-Day Effects on Short-Duration Maximal Exercise Performance. Sci Rep. 2020 Jun 11;10(1):9485. PMID: 32528038; PMCID: PMC7289891. DOI: https://doi.org/10.1038/s41598-020-66342-w

Cornelissen G, Otsuka K. Chronobiology of Aging: A Mini-Review. Gerontology. 2017;63(2):118-128. Epub 2016 Oct 22. PMID: 27771728. DOI: https://doi.org/10.1159/000450945

Zhao J, Warman GR, Cheeseman JF. The functional changes of the circadian system organization in aging. Ageing Res Rev. 2019 Jul;52:64-71. Epub 2019 Apr 29. PMID: 31048031. DOI: https://doi.org/10.1016/j.arr.2019.04.006

Cipolla-Neto J, Amaral FGD. Melatonin as a Hormone: New Physiological and Clinical Insights. Endocr Rev. 2018 Dec 1;39(6):990-1028. PMID: 30215696. DOI: https://doi.org/10.1210/er.2018-00084

Khullar, A. The role of melatonin in the circadian rhythm sleep-wake cycle. Psychiatric Times. 2012;29(7):26-27,30-32.

Yoshida K, Hashiramoto A, Okano T, Yamane T, Shibanuma N, Shiozawa S. TNF-α modulates expression of the circadian clock gene Per2 in rheumatoid synovial cells. Scand J Rheumatol. 2013;42(4):276-80. Epub 2013 Mar 16. PMID: 23496259. DOI: https://doi.org/10.3109/03009742.2013.765031

Yoshida K, Nakai A, Kaneshiro K, Hashimoto N, Suzuki K, Uchida K, Hashimoto T, Kawasaki Y, Tateishi K, Nakagawa N, Shibanuma N, Sakai Y, Hashiramoto A. TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells. Biochem Biophys Res Commun. 2018 Jan 8;495(2):1675-1680. Epub 2017 Dec 5. PMID: 29217191. DOI: https://doi.org/10.1016/j.bbrc.2017.12.015

Narasimamurthy R, Hatori M, Nayak SK, Liu F, Panda S, Verma IM. Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12662-7. Epub 2012 Jul 9. PMID: 22778400; PMCID: PMC3411996. DOI: https://doi.org/10.1073/pnas.1209965109

Spengler ML, Kuropatwinski KK, Comas M, Gasparian AV, Fedtsova N, Gleiberman AS, Gitlin II, Artemicheva NM, Deluca KA, Gudkov AV, Antoch MP. Core circadian protein CLOCK is a positive regulator of NF-κB-mediated transcription. Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):E2457-65. Epub 2012 Aug 15. PMID: 22895791; PMCID: PMC3443185. DOI: https://doi.org/10.1073/pnas.1206274109

de Souza Teixeira AA, Lira FS, Rosa-Neto JC. Aging with rhythmicity. Is it possible? Physical exercise as a pacemaker. Life Sci. 2020 Nov 15;261:118453. Epub 2020 Sep 18. PMID: 32956663; PMCID: PMC7500276. DOI: https://doi.org/10.1016/j.lfs.2020.118453

Gabriel BM, Zierath JR. Circadian rhythms and exercise - re-setting the clock in metabolic disease. Nat Rev Endocrinol. 2019 Apr;15(4):197-206. PMID: 30655625. DOI: https://doi.org/10.1038/s41574-018-0150-x

Choi Y, Cho J, No MH, Heo JW, Cho EJ, Chang E, Park DH, Kang JH, Kwak HB. Re-Setting the Circadian Clock Using Exercise against Sarcopenia. Int J Mol Sci. 2020 Apr 28;21(9):3106. PMID: 32354038; PMCID: PMC7247148. DOI: https://doi.org/10.3390/ijms21093106

Schmitt EE, Johnson EC, Yusifova M, Bruns DR. The renal molecular clock: broken by aging and restored by exercise. Am J Physiol Renal Physiol. 2019 Nov 1;317(5):F1087-F1093. Epub 2019 Aug 28. PMID: 31461350; PMCID: PMC6879930. DOI: https://doi.org/10.1152/ajprenal.00301.2019

Gaskell SK, Rauch CE, Parr A, Costa RJS. Diurnal versus Nocturnal Exercise-Effect on the Gastrointestinal Tract. Med Sci Sports Exerc. 2021 May 1;53(5):1056-1067. PMID: 33065594. DOI: https://doi.org/10.1249/MSS.0000000000002546

Youngstedt SD, Elliott JA, Kripke DF. Human circadian phase-response curves for exercise. J Physiol. 2019 Apr;597(8):2253-2268. Epub 2019 Mar 18. PMID: 30784068; PMCID: PMC6462487. DOI: https://doi.org/10.1113/JP276943

Elbaz M, Yauy K, Metlaine A, Martoni M, Léger D. Validation of a new actigraph motion watch versus polysomnography on 70 healthy and suspected sleepdisordered subjects. In Universite Paris Descartes. 2012. (Vol. 21, Issue 2001).

Littner M, Kushida CA, Anderson WM, Bailey D, Berry RB, Davila DG, Hirshkowitz M, Kapen S, Kramer M, Loube D, Wise M, Johnson SF; Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the role of actigraphy in the study of sleep and circadian rhythms: an update for 2002. Sleep. 2003 May 1;26(3):337-41. PMID: 12749556. DOI: https://doi.org/10.1093/sleep/26.3.337

Folkard S, Monk TH, Lobban MC. Towards a predictive test of adjustment to shift work. Ergonomics. 1979 Jan;22(1):79-91. PMID: 436816. DOI: https://doi.org/10.1080/00140137908924591

Sousa VD, Rojjanasrirat W. Translation, adaptation and validation of instruments or scales for use in cross-cultural health care research: a clear and user-friendly guideline. J Eval Clin Pract. 2011 Apr;17(2):268-74. Epub 2010 Sep 28. PMID: 20874835. DOI: https://doi.org/10.1111/j.1365-2753.2010.01434.x

Bily W, Franz C, Trimmel L, Loefler S, Cvecka J, Zampieri S, Kasche W, Sarabon N, Zenz P, Kern H. Effects of Leg-Press Training With Moderate Vibration on Muscle Strength, Pain, and Function After Total Knee Arthroplasty: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2016 Jun;97(6):857-65. Epub 2016 Jan 4. PMID: 26763947. DOI: https://doi.org/10.1016/j.apmr.2015.12.015

Kralik M, Cvecka J, Buzgo G, Putala M, Ukropcova B, Ukropec J, Killinger Z, Payer J, Kollarik B, Bujdak P, Raastad T, Sedliak M. Strength training as a supplemental therapy for androgen deficiency of the aging male (ADAM): study protocol for a three-arm clinical trial. BMJ Open. 2019 Sep 5;9(9):e025991. PMID: 31492775; PMCID: PMC6731925. DOI: https://doi.org/10.1136/bmjopen-2018-025991

Sarabon N, Rosker J, Fruhmann H, Burggraf S, Loefler S, Kern H. Reliability of maximal voluntary contraction related parameters measured by a novel portable isometric knee dynamometer. Phys Medizin Rehabil Kurortmedizin. 2013;23(1). DOI: https://doi.org/10.1055/s-0032-1331190

Sarabon N, Loefler S, Cvecka J, Sedliak M, Kern H. Strength training in elderly people improves static balance: a randomized controlled trial. Eur J Transl Myol. 2013;23(3). DOI: https://doi.org/10.4081/bam.2013.3.85

Shanely RA, Zwetsloot KA, Triplett NT, Meaney MP, Farris GE, Nieman DC. Human skeletal muscle biopsy procedures using the modified Bergström technique. J Vis Exp. 2014 Sep 10;(91):51812. PMID: 25285722; PMCID: PMC4828068. DOI: https://doi.org/10.3791/51812

Lavin KM, Perkins RK, Jemiolo B, Raue U, Trappe SW, Trappe TA. Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation. J Appl Physiol (1985). 2020 Jan 1;128(1):87-99. Epub 2019 Nov 21. PMID: 31751180; PMCID: PMC6985808. DOI: https://doi.org/10.1152/japplphysiol.00495.2019

Hopkins WG. A scale of magnitudes for effect statistics. Sportscience. 2002;5.

Hopkins WG, Marshall SW, Batterham AM, Hanin J. Progressive statistics for studies in sports medicine and exercise science. Med Sci Sports Exerc. 2009 Jan;41(1):3-13. PMID: 19092709. DOI: https://doi.org/10.1249/MSS.0b013e31818cb278

Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013 Jan 8;346:e7586. PMID: 23303884; PMCID: PMC3541470. DOI: https://doi.org/10.1136/bmj.e7586

Berisha, G., Sedliak, M., Zeman, M., Hamar, D., Cvečka, J., Tirpáková, V., Vajda, M., Oreská, Ľudmila, Černáčková, A., Čupka, M., Šarabon, N., Protasi, F., Zampieri, S., Kern, H., Lofler, S., Musaro, A., Stebelová, K., & Okuliarová, M. (2023). Can lifelong endurance exercise improve ageing through beneficial effects on circadian timing function, muscular performance and health status in men? Protocol for a comparative cross-sectional study. European Journal of Translational Myology, 33(4). https://doi.org/10.4081/ejtm.2023.12012

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