Eight weeks of high-intensity interval training and aerobic continues training increase serum telomerase, sirt6, and irisin level in healthy elderly men

Document Type : Research Paper


1 1 Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran

2 Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences


Background: Telomerase activity plays a key role in preserving telomere length which is important in cellular aging. There is evidence showing the link between sirt6, irisin, and telomerase activity.  
Aim: The aim of this study was to compare the effect of 8 weeks of high-intensity interval training (HIIT) and aerobic continuous training (ACT) on telomerase activity, sirt6, and irisin levels of healthy older adults.
Materials and Methods: Thirty healthy males (age: 60-70 years, weight: 68-72 kg) participated voluntarily to follow the 8-week program including 3 sessions per week. Rest ratio in HIIT training was 1:2 and the intensity corresponded to 90% of HRR. ACT intensity was progressive starting with 50% of HRR and finishing with 70% of HRR. Blood samples were taken in a 12-hour fasting situation, before and after the program.
Results: Results showed a significant effect of training on serum telomerase and sirt6 in training groups, not the control group. Also, in comparison to ACT and the control group, serum irisin was significantly higher in the HIIT group.
Conclusion: We concluded HIIT training is safe and efficient for older adults in terms of telomerase activity, sirt6, and irisin level and can be followed as a time-efficient training protocol.


[1] Guan Y, Yan Z. “Molecular mechanisms of exercise and healthspan”. Cells. 2022; 11(5): 872.

[2] Ludlow AT, Zimmerman JB, Witkowski S, Hearn JW, Hatfield BD, Roth SM. “Relationship between physical activity level, telomere length, and telomerase activity”. Medicine and Science in Sports and Exercise. 2008; 40(10): 1764-71. https://doi.org/10.1249/mss.0b013e31817c92aa.

[3] Benetos A, Okuda K, Lajemi M, Kimura M, Thomas F, Skurnick J, Labat C, Bean K, Aviv A. “Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity”. Hypertension. 2001; 37(2): 381-385. https://doi.org/10.1161/01.hyp.37.2.381.

[4] Blackburn EH. “Telomere states and cell fates”. Nature. 2000; 408(6808): 53-56. https://doi.org/10.1038/35040500.

[5] Demissie S, Levy D, Benjamin EJ, Cupples LA, Gardner JP, Herbert A, Kimura M, Larson MG, Meigs JB, Keaney JF, Aviv A.. “Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men" from the Framingham Heart Study”. Aging cell. 2006; 5(4): 325-330. https://doi.org/10.1111/j.1474-9726.2006.00224.x.

[6] Zvereva M, Shcherbakova D, Dontsova O. “Telomerase: structure, functions, and activity regulation”. Biochemistry (Moscow). 2010; 75(13): 1563-1583. https://doi.org/10.1134/s0006297910130055.

[7] Koltai E, Szabo Z, Atalay M, Boldogh I, Naito H, Goto S, Nyakas C, Radak Z. “Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats”. Mechanisms of Ageing and Development. 2010; 131(1): 21-28. https://doi.org/10.1016/j.mad.2009.11.002.

[8] Michishita E, McCord RA, Boxer LD, Barber MF, Hong T, Gozani O, Chua KF. “Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6”. Cell Cycle. 2009; 8(16): 2664-2666. https://doi.org/10.4161/cc.8.16.9367.

[9] Baur JA, Zou Y, Shay JW, Wright WE. T. “Telomere position effect in human cells”. Science. 2001; 292(5524): 2075-2077. https://doi.org/10.1126/science.1062329.

[10] McCord RA, Michishita E, Hong T, Berber E, Boxer LD, Kusumoto R, Guan S, Shi X, Gozani O, Burlingame AL, Bohr VA. “SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair”. Aging (Albany NY). 2009; 1(1): 109. https://doi.org/10.18632/aging.100011.

[11] Kaminsky LA, German C, Imboden M, Ozemek C, Peterman JE, Brubaker PH. “The importance of healthy lifestyle behaviors in the prevention of cardiovascular disease”. Progress in Cardiovascular Diseases. 2022; 70: 8-15. https://doi.org/10.1016/j.pcad.2021.12.001.

[12] Melk A, Tegtbur U, Hilfiker-Kleiner D, Eberhard J, Saretzki G, Eulert C, Kerling A, Nelius AK, Hömme M, Strunk D, Berliner D. “Improvement of biological age by physical activity”. International Journal of Cardiology. 2014; 176(3): 1187-1189.

[13] Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S.. “A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis”. Nature. 2012; 481(7382): 463. https://doi.org/10.1016/j.yend.2012.04.012.

[14] Khavinson VK, Kuznik BI, Tarnovskaya SI, Lin’kova NS.. “Short peptides and telomere length regulator hormone irisin”. Bulletin of Experimental Biology and Medicine. 2016; 160(3): 347-349. https://doi.org/10.1007/s10517-016-3167-y.

[15] Rana KS, Arif M, Hill EJ, Aldred S, Nagel DA, Nevill A, Randeva HS, Bailey CJ, Bellary S, Brown JE.. “Plasma irisin levels predict telomere length in healthy adults”. Age. 2014; 36(2): 995-1001. https://doi.org/10.1007/s11357-014-9620-9.

[16] Radak Z, et al. “Telomerase activity is not altered by regular strenuous exercise in skeletal muscle or by sarcoma in liver of rats”. Redox Report. 2001; 6(2): 99-103. https://doi.org/10.1179/135100001101536102.

[17] Liang C, Zhou X, Li M, Song Z, Lan J. “Effects of treadmill exercise on mitochondrial DNA damage and cardiomyocyte telomerase activity in aging model rats based on classical apoptosis signaling pathway”. BioMed Research International. 2022; 3529499. https://doi.org/10.1155/2022/3529499.

[18] Werner CM, Hecksteden A, Morsch A, Zundler J, Wegmann M, Kratzsch J, Thiery J, Hohl M, Bittenbring JT, Neumann F, Böhm M. “Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study”. European Heart Journal. 2018; 40(1): 34-46. https://doi.org/10.1093/eurheartj/ehy585.

[19] Tennen RI, Bua DJ, Wright WE, Chua KF. “SIRT6 is required for maintenance of telomere position effect in human cells”. Nature Communications. 2011; 2: 433. https://doi.org/10.1038/ncomms1443.

[20] Selamoglu Z, Hajipour S, Khan QA, Ahandani EA. “The effects on antiaging molecules of physical exercise”. Bioengineering Studies. 2022; 3(1): 28-32.

[21] Keyvani F, Kordi MR, Maghbooli Taghidizaj Z, Shabkhiz F. “The effect of eight weeks high intensity interval training on serum levels of telomerase enzyme and sirtuin 6 protein in aged men”. Sport Physiology. 2020; 12(45): 17-30. https://doi.org/10.52547/joeppa.15.2.95

[22] Sanders JL, Newman AB. “Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither?”. Epidemiologic Reviews. 2013; 35(1): 112-131. https://doi.org/10.1093/epirev/mxs008.

[23] Puterman E, Lin J, Blackburn E, O’Donovan A, Adler N, Epel E. “The power of exercise: buffering the effect of chronic stress on telomere length”. PloS one. 2010; 5(5): e10837. https://doi.org/10.1371/journal.pone.0010837.

[24] Sjögren P, Fisher R, Kallings L, Svenson U, Roos G, Hellénius M. “Stand up for health—avoiding sedentary behaviour might lengthen your telomeres: secondary outcomes from a physical activity RCT in older people”. Br J Sports Med. 2014; 48(19): 1407-1409. https://doi.org/10.1136/bjsports-2013-093342.

[25] Wang Y, Feigon J. “Structural biology of telomerase and its interaction at telomeres”. Current Opinion in Structural Biology. 2017; 47: 77-87. https://doi.org/10.1016/j.sbi.2017.06.010.

[26] Chen N, Li Q, Liu J, Jia Sh. “Irisin, an exercise‐induced myokine as a metabolic regulator: an updated narrative review”. Diabetes/ Metabolism Research and Reviews. 2016; 32(1): 51-59. https://doi.org/10.1002/dmrr.2660.

[27] Cunha A. “Basic research: Irisin—behind the benefits of exercise”. Nature Reviews Endocrinology. 2012; 8(4): 195. https://doi.org/10.1038/nrendo.2012.11.

[28] Norheim F, Langlwite TM, Hjorth M, Holen T, et al. “The effects of acute and chronic exercise on PGC‐1α, irisin and browning of subcutaneous adipose tissue in humans”. The FEBS Journal. 2014; 281(3): 739-749. https://doi.org/10.1111/febs.12619.

[29] Sánchez B, Muñoz-Pinto MF, Cano M. “Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase”. Expert Reviews in Molecular Medicine. 2023; 25: e4. https://doi.org/10.1017/erm.2022.41.

[30] Lombard DB, Schwer B, Alt FW, Mostoslavsky R. “SIRT6 in DNA repair, metabolism and ageing”. Journal of Internal Medicine. 2008; 263(2): 128-141. https://doi.org/10.1111/j.1365-2796.2007.01902.x.

[31] Jia G, Su L, Singhal S, Liu X. “Emerging roles of SIRT6 on telomere maintenance, DNA repair, metabolism and mammalian aging”. Molecular and Cellular Biochemistry. 2012; 364(1-2): 345-350. https://doi.org/10.1007/s11010-012-1236-8.

[32] Hipkiss AR, “Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms?”. Biogerontology. 2008; 9(1): 49-55. https://doi.org/10.1007/s10522-007-9110-x.

[33] Song S, Lee E, Kim H. “Does exercise affect telomere length? A systematic review and meta-analysis of randomized controlled trials”. Medicina. 2022; 58(2): 242. https://doi.org/10.3390/medicina58020242.

[34] Von Zglinicki T. “Oxidative stress shortens telomeres”. Trends in Biochemical Sciences. 2002; 27(7): 339-344. https://doi.org/10.1016/s0968-0004(02)02110-2.

[35] Sousa-Victor P, García-Prat L, Serrano AL, Perdiguero E, Muñoz-Cánoves P. “Muscle stem cell aging: regulation and rejuvenation”. Trends in Endocrinology & Metabolism. 2015; 26(6): 287-296. https://doi.org/10.1016/j.tem.2015.03.006.