Journal of Sports and Biomotor Sciences

Journal of Sports and Biomotor Sciences

Neuromuscular indices adaptation of sarcopenic elderly men to high-intensity interval training and L-citrulline supplementation

Document Type : Original Article

Authors
Amin Farzaneh hesari 1
Solmaz Mhdavi ortakand 2
Bahareh Samadi 3
1 Assistant Professor of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran
2 Ph.D, Corrected exercise, Tehran university, Tehran, Iran
3 M.Sc of Sports Physiology, Department of Sports Science, Sari Branch, Islamic Azad University, Sari, Iran
10.22034/sbs.2023.372342.0
Abstract
Introduction and purpose: Aging causes the decreased of muscle mass, strength, and or limited activity known as sarcopenia in the elderly. Therefore, the purpose of this study was to determine the effects of eight weeks of high-intensity interval and L-citrulline supplementation on serum CAF and neuromuscular indices in elderly men with sarcopenia.
Materials and Methods: In this randomized clinical trial, 41 elderly men with sarcopenia randomly divided into four groups: high-intensity interval training+placebo (HIIT), citrolin (CIT) and high-intensity interval training+citrolin (HIIT+CIT) and placebo (P). HIIT was performed for 8 weeks and 2 sessions per week that included 30 seconds cycling exercise on ergometer (intensity of 85-90% HR reserve). CIT supplement consumed in single 6 g-dose alternative day. Pre and post-training intervention, neuromuscular indices (muscle quality, chair sitting-standing time, timed up and go) were measured and blood sample (CAF) were taken. Repeated measures ANOVA and Bonferroni post hoc tests was used for data analysis.
Results: Results showed that there was significant decrease for CAF and significant increase for muscle quality and sitting-standing time in HIIT+CIT and HIIT than P (P<0.05). Lean mass index and walking speed significantly improved in HIIT+CIT and HIIT than P (P<0.05).
Discussion and Conclusion: In conclusion, HIIT with two sessions per week frequency improved neuromuscular indices in sarcopenic elderly men and therefore, can be considered an effective method to prevent or reduce sarcopenia.

Highlights

Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with
functional impairment and physical disability. J Am Geriatr Soc. 2002; 50(5):889-96.
2. Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB. Sarcopenia: etiology, clinical consequences,
intervention, and assessment. Osteoporos Int. 2010; 21(4):543-59.
3. Pratt J, Boreham C, Ennis S, Ryan AW, De Vito G. Genetic associations with aging muscle: a systematic review. Cells.
2019; 9(1):12-19.
4. Wu R, De Vito G, Delahunt E, Ditroilo M. Age-related changes in motor function (I). Mechanical and neuromuscular
factors. Int J Sports Med. 2020; 41(11):709-719.
5. Jang YC, Van Remmen H. Age-associated alterations of the neuromuscular junction. Exp Gerontol. 2011; 46(2):193-198.
6. Lepore E, Casola I, Dobrowolny G, Musarò A. Neuromuscular junction as an entity of nerve-muscle communication.
Cells. 2019; 8(8): E906.
7. Punga AR, Ruegg MA. Signaling and aging at the neuromuscular synapse: Lessons learnt from neuromuscular diseases.
Curr Opin Pharmacol. 2012; 12(3), 340-46.
8. Butikofer L, Zurlinden A, Bolliger MF, Kunz B, Sonderegger P. Destabilization of the neuromuscular junction by
proteolytic cleavage of agrin results in precocious sarcopenia. FASEB J. 2011; 25(12), 4378-93.
9. Bondoc I, Cochrane SK, Church TS, Dahinden P, Hettwer S, Hsu FC, et al. Effects of a one-year physical activity
program on serum c-terminal agrin fragment (CAF) concentrations among mobility-limited older adults. J Nut Health
Aging, 2015; 19(9), 922-27.
10. Drey M, Sieber CC, Bauer JM, Uter W, Dahinden P, Fariello RG, et al. C-terminal Agrin Fragment as a potential marker
for sarcopenia caused by degeneration of the neuromuscular junction. Exp. Gerontol. 2013; 48(1), 76-8.
11. Landi R, Calvani M, Lorenzi AM, Martone M, Tosato M, et al. Serum levels of c-terminal agrin fragment (CAF) are
associated with sarcopenia in older multimorbid community-dwellers: results from the ilsirente study. Exp. Gerontol.
2016; 79, 31-36.
12. Bhasin S, He EJ, Kawakubo M, Schroeder ET, Yarasheski K, Opiteck GJ, et al. N-terminal propeptide of type III
procollagen as a biomarker of anabolic response to recombinant human GH and testosterone. Clin Endocrinol Metab,
2009; 94(11), 4224-33.
13. Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low‐volume, high‐intensity interval
training in health and disease. J. physiol. 2012; 590(5):1077-84.
14. Tschopp M, Sattelmayer MK, Hilfiker R. Is power training or conventional resistance training better for function in
elderly persons? A meta-analysis. Age Ageing. 2011; 40(5):549-56.
15. Coetsee C, Terblanche E. The effect of three different exercise training modalities on cognitive and physical function in a healthy older population. Eur Rev Aging Phys Act. 2017; 14(1):13.
16. Buckinx F, Gouspillou G, Carvalho LP, Marcangeli V, El Hajj Boutros G, Dulac M, et al. Effect of high-intensity
interval training combined with l-citrulline supplementation on functional capacities and muscle function in dynapenicobese older adults. J clin Med. 2018; 7(12):561.
17. Sculthorpe NF, Herbert P, Grace F. One session of high-intensity interval training (HIIT) every 5 days, improves muscle
power but not static balance in lifelong sedentary ageing men: a randomized controlled trial. Medicine. 2017;
96(6):e6040
18. Hoseinzadeh F, Farzaneh Hesari A. Effects of low-frequency High-Intensity Interval training combined with L-Citrulline
supplementation on myostatin and some physiological parameters in inactive elderly men. Sport Biosciences. 2020;
12(4):493-506. [In Persian]
19. van de Poll MC, Soeters PB, Deutz NE, Fearon KC, Dejong CH. Renal metabolism of amino acids: its role in interorgan
amino acid exchange. Am j Clin Nnutr. 2004; 79(2):185-197.
20. Moinard C, Maccario J, Walrand S, Lasserre V, Marc J, Boirie Y, et al. Arginine behaviour after arginine or citrulline
administration in older subjects. Br. J. Nutr. 2016; 115(3):399-404.
21. Moinard C, Le Plenier S, Noirez P, Morio B, Bonnefont-Rousselot D, Kharchi C, et al. Citrulline supplementation
induces changes in body composition and limits age-related metabolic changes in healthy male rats. J Nutr. 2015;
145(7):1429-1437.
22. Bouillanne O, Melchior J-C, Faure C, Paul M, Canouï-Poitrine F, Boirie Y, et al. Impact of 3-week citrulline
supplementation on postprandial protein metabolism in malnourished older patients: The Ciproage randomized controlled trial. Clin Nutr. 2019; 38(2):564-76.
23. Fragala MS, Jajtner AR, Beyer KS, Townsend JR, Emerson S, Scanlon TC, et al. Biomarkers of muscle quality:
N‐terminal propeptide of type III procollagen and C‐terminal agrin fragment responses to resistance exercise training
in older adults. J Cachexia Sarcopenia Muscle. 2014; 5(2), 139-48.
24. Willoughby DS, Beretich KN, Chen M, Funderburk LK. Decreased serum levels of C-terminal agrin in
postmenopausal women following resistance training. Aging Phys Act. 2020; 28(1):73–80.
25. Sharifi Mogadam A, Askari R, Haghighi AH. The Effect of Resistance Training with and without Blood Flow Restriction
on Serum Concentration of CAF, P3NP and Muscular Function in Elderly Women. sport biosciences. 2018; 10(3):17. [In
Persian]
26. Bigdelia S, Dehghaniyana MH, Amani-Shalamzaria S, Rajabia H, Gahreman DE. Functional training with blood
occlusion influences muscle quality indices in older adults. Arch. Gerontol. Geriatr. 2020; 90:104-110.
27. Campo Cervantes J, Macías Cervantes JH , Monroy Torres R. Effect of a resistance training program on sarcopenia and
functionality of the older adults living in a nursing home. J Nutr Health Aging. 2019; 23(9):829-836.
28. Gonzales JU, Raymond A, Ashley J, Kim Y. Does l‐citrulline supplementation improve exercise blood flow in older
adults? Expe physiol. 2017; 102(12):1661-71.
29. Fragala M, Fukuda D, Stout J, Townsend J, Emerson N, Boone C, et al. Muscle quality index improves with resistance
exercise training in older adults. Exp Gerontolo. 2014; 53:1-6.
30. Vikberg S, Sörlén N, Brandén L, Johansson J, Nordström A, Hult A, et al. Effects of Resistance Training on Functional
Strength and Muscle Mass in 70-Year-Old Individuals With Pre-sarcopenia: A Randomized Controlled Trial. Am Med
Dir Assoc. 2019; 20(1): 28-34.
31. Cooper C, Fielding R, Visser M, Van Loon LJ, Rolland Y, Orwoll E, et al. Tools in the assessment of sarcopenia. Calcif
Tissue Int. 2013; 93(3): 201-210.
32. Coburn JW, Malek MH. NSCA's essentials of personal training: USA: Human Kinetics; 2012. 164-171.
33. Fragala MS, Kenny AM, Kuchel GA. Muscle quality in aging: a multidimensional approach to muscle functioning with
applications for treatment. Sports Med. 2015; 45(5):641-58.
34. Kargaran A, Abedinpour A, Saadatmehr Z, Yaali R, Amani-Shalamzari S, Gahreman D. Effects of dual-task training
with blood flow restriction on cognitive functions, muscle quality, and circulatory biomarkers in elderly women. Physiol
Behav. 2021; 239,1-9.
35. Deschenes MR, Roby MR, Eason MK, Harris MB. Remodeling of the neuromuscular junction precedes sarcopenia
related alterations in myofibers. Exp Gerontol. 2010; 45(5),389-93.
36. Banitalebi E, Faramarzi M, Ghahfarokhi MM, SavariNikoo F, Soltani N, Bahramzadeh A. Osteosarcopenic obesity
markers following elastic band resistance training: a randomized controlled trial. Exp. Gerontol. 2020; 135:110884.
37. Goodpaster BH, Park S, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength,
mass, and quality in older adults: the health, aging and body composition study. Gerontol. A Biol. Sci. Med. Sci. 2006;
61(10):1059-64.
38. Ozaki H, Kakigi R, Kobayashi H, Loenneke JP, Abe A, Naito H. Effects of walking combined with restricted leg blood
flow on mtor and mapk signalling in young men. Acta. Physiol. 2014; 211(1):97-106.
39. Barry E, Galvin R, Keogh C, Horgan F, Fahey T. Is the timed up and go test a useful predictor of risk of falls in
community dwelling older adults: a systematic review and meta-analysis. BMC. Geriatr. 2014; 14:14.
40. Muehlbauer T, Gollhofer A, Granacher U. Associations between measures of balance and lower-extremity muscle
strength/power in healthy individuals across the lifespan: a systematic review and meta-analysis. Sport. Med. 2015:
45(12):1671-1692.
41. Figueroa A, Alvarez-Alvarado S, Ormsbee MJ, Madzima TA, Campbell JC, Wong A. Impact of L-citrulline
supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressure. Exp gerontol. 2015; 63:35-40

Keywords
Interval training
Muscle quality
Citrolin
Sarcopenia
Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with
functional impairment and physical disability. J Am Geriatr Soc. 2002; 50(5):889-96.
2. Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB. Sarcopenia: etiology, clinical consequences,
intervention, and assessment. Osteoporos Int. 2010; 21(4):543-59.
3. Pratt J, Boreham C, Ennis S, Ryan AW, De Vito G. Genetic associations with aging muscle: a systematic review. Cells.
2019; 9(1):12-19.
4. Wu R, De Vito G, Delahunt E, Ditroilo M. Age-related changes in motor function (I). Mechanical and neuromuscular
factors. Int J Sports Med. 2020; 41(11):709-719.
5. Jang YC, Van Remmen H. Age-associated alterations of the neuromuscular junction. Exp Gerontol. 2011; 46(2):193-198.
6. Lepore E, Casola I, Dobrowolny G, Musarò A. Neuromuscular junction as an entity of nerve-muscle communication.
Cells. 2019; 8(8): E906.
7. Punga AR, Ruegg MA. Signaling and aging at the neuromuscular synapse: Lessons learnt from neuromuscular diseases.
Curr Opin Pharmacol. 2012; 12(3), 340-46.
8. Butikofer L, Zurlinden A, Bolliger MF, Kunz B, Sonderegger P. Destabilization of the neuromuscular junction by
proteolytic cleavage of agrin results in precocious sarcopenia. FASEB J. 2011; 25(12), 4378-93.
9. Bondoc I, Cochrane SK, Church TS, Dahinden P, Hettwer S, Hsu FC, et al. Effects of a one-year physical activity
program on serum c-terminal agrin fragment (CAF) concentrations among mobility-limited older adults. J Nut Health
Aging, 2015; 19(9), 922-27.
10. Drey M, Sieber CC, Bauer JM, Uter W, Dahinden P, Fariello RG, et al. C-terminal Agrin Fragment as a potential marker
for sarcopenia caused by degeneration of the neuromuscular junction. Exp. Gerontol. 2013; 48(1), 76-8.
11. Landi R, Calvani M, Lorenzi AM, Martone M, Tosato M, et al. Serum levels of c-terminal agrin fragment (CAF) are
associated with sarcopenia in older multimorbid community-dwellers: results from the ilsirente study. Exp. Gerontol.
2016; 79, 31-36.
12. Bhasin S, He EJ, Kawakubo M, Schroeder ET, Yarasheski K, Opiteck GJ, et al. N-terminal propeptide of type III
procollagen as a biomarker of anabolic response to recombinant human GH and testosterone. Clin Endocrinol Metab,
2009; 94(11), 4224-33.
13. Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low‐volume, high‐intensity interval
training in health and disease. J. physiol. 2012; 590(5):1077-84.
14. Tschopp M, Sattelmayer MK, Hilfiker R. Is power training or conventional resistance training better for function in
elderly persons? A meta-analysis. Age Ageing. 2011; 40(5):549-56.
15. Coetsee C, Terblanche E. The effect of three different exercise training modalities on cognitive and physical function in a healthy older population. Eur Rev Aging Phys Act. 2017; 14(1):13.
16. Buckinx F, Gouspillou G, Carvalho LP, Marcangeli V, El Hajj Boutros G, Dulac M, et al. Effect of high-intensity
interval training combined with l-citrulline supplementation on functional capacities and muscle function in dynapenicobese older adults. J clin Med. 2018; 7(12):561.
17. Sculthorpe NF, Herbert P, Grace F. One session of high-intensity interval training (HIIT) every 5 days, improves muscle
power but not static balance in lifelong sedentary ageing men: a randomized controlled trial. Medicine. 2017;
96(6):e6040
18. Hoseinzadeh F, Farzaneh Hesari A. Effects of low-frequency High-Intensity Interval training combined with L-Citrulline
supplementation on myostatin and some physiological parameters in inactive elderly men. Sport Biosciences. 2020;
12(4):493-506. [In Persian]
19. van de Poll MC, Soeters PB, Deutz NE, Fearon KC, Dejong CH. Renal metabolism of amino acids: its role in interorgan
amino acid exchange. Am j Clin Nnutr. 2004; 79(2):185-197.
20. Moinard C, Maccario J, Walrand S, Lasserre V, Marc J, Boirie Y, et al. Arginine behaviour after arginine or citrulline
administration in older subjects. Br. J. Nutr. 2016; 115(3):399-404.
21. Moinard C, Le Plenier S, Noirez P, Morio B, Bonnefont-Rousselot D, Kharchi C, et al. Citrulline supplementation
induces changes in body composition and limits age-related metabolic changes in healthy male rats. J Nutr. 2015;
145(7):1429-1437.
22. Bouillanne O, Melchior J-C, Faure C, Paul M, Canouï-Poitrine F, Boirie Y, et al. Impact of 3-week citrulline
supplementation on postprandial protein metabolism in malnourished older patients: The Ciproage randomized controlled trial. Clin Nutr. 2019; 38(2):564-76.
23. Fragala MS, Jajtner AR, Beyer KS, Townsend JR, Emerson S, Scanlon TC, et al. Biomarkers of muscle quality:
N‐terminal propeptide of type III procollagen and C‐terminal agrin fragment responses to resistance exercise training
in older adults. J Cachexia Sarcopenia Muscle. 2014; 5(2), 139-48.
24. Willoughby DS, Beretich KN, Chen M, Funderburk LK. Decreased serum levels of C-terminal agrin in
postmenopausal women following resistance training. Aging Phys Act. 2020; 28(1):73–80.
25. Sharifi Mogadam A, Askari R, Haghighi AH. The Effect of Resistance Training with and without Blood Flow Restriction
on Serum Concentration of CAF, P3NP and Muscular Function in Elderly Women. sport biosciences. 2018; 10(3):17. [In
Persian]
26. Bigdelia S, Dehghaniyana MH, Amani-Shalamzaria S, Rajabia H, Gahreman DE. Functional training with blood
occlusion influences muscle quality indices in older adults. Arch. Gerontol. Geriatr. 2020; 90:104-110.
27. Campo Cervantes J, Macías Cervantes JH , Monroy Torres R. Effect of a resistance training program on sarcopenia and
functionality of the older adults living in a nursing home. J Nutr Health Aging. 2019; 23(9):829-836.
28. Gonzales JU, Raymond A, Ashley J, Kim Y. Does l‐citrulline supplementation improve exercise blood flow in older
adults? Expe physiol. 2017; 102(12):1661-71.
29. Fragala M, Fukuda D, Stout J, Townsend J, Emerson N, Boone C, et al. Muscle quality index improves with resistance
exercise training in older adults. Exp Gerontolo. 2014; 53:1-6.
30. Vikberg S, Sörlén N, Brandén L, Johansson J, Nordström A, Hult A, et al. Effects of Resistance Training on Functional
Strength and Muscle Mass in 70-Year-Old Individuals With Pre-sarcopenia: A Randomized Controlled Trial. Am Med
Dir Assoc. 2019; 20(1): 28-34.
31. Cooper C, Fielding R, Visser M, Van Loon LJ, Rolland Y, Orwoll E, et al. Tools in the assessment of sarcopenia. Calcif
Tissue Int. 2013; 93(3): 201-210.
32. Coburn JW, Malek MH. NSCA's essentials of personal training: USA: Human Kinetics; 2012. 164-171.
33. Fragala MS, Kenny AM, Kuchel GA. Muscle quality in aging: a multidimensional approach to muscle functioning with
applications for treatment. Sports Med. 2015; 45(5):641-58.
34. Kargaran A, Abedinpour A, Saadatmehr Z, Yaali R, Amani-Shalamzari S, Gahreman D. Effects of dual-task training
with blood flow restriction on cognitive functions, muscle quality, and circulatory biomarkers in elderly women. Physiol
Behav. 2021; 239,1-9.
35. Deschenes MR, Roby MR, Eason MK, Harris MB. Remodeling of the neuromuscular junction precedes sarcopenia
related alterations in myofibers. Exp Gerontol. 2010; 45(5),389-93.
36. Banitalebi E, Faramarzi M, Ghahfarokhi MM, SavariNikoo F, Soltani N, Bahramzadeh A. Osteosarcopenic obesity
markers following elastic band resistance training: a randomized controlled trial. Exp. Gerontol. 2020; 135:110884.
37. Goodpaster BH, Park S, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength,
mass, and quality in older adults: the health, aging and body composition study. Gerontol. A Biol. Sci. Med. Sci. 2006;
61(10):1059-64.
38. Ozaki H, Kakigi R, Kobayashi H, Loenneke JP, Abe A, Naito H. Effects of walking combined with restricted leg blood
flow on mtor and mapk signalling in young men. Acta. Physiol. 2014; 211(1):97-106.
39. Barry E, Galvin R, Keogh C, Horgan F, Fahey T. Is the timed up and go test a useful predictor of risk of falls in
community dwelling older adults: a systematic review and meta-analysis. BMC. Geriatr. 2014; 14:14.
40. Muehlbauer T, Gollhofer A, Granacher U. Associations between measures of balance and lower-extremity muscle
strength/power in healthy individuals across the lifespan: a systematic review and meta-analysis. Sport. Med. 2015:
45(12):1671-1692.
41. Figueroa A, Alvarez-Alvarado S, Ormsbee MJ, Madzima TA, Campbell JC, Wong A. Impact of L-citrulline
supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressure. Exp gerontol. 2015; 63:35-40

  • Receive Date 14 October 2022
  • Revise Date 07 January 2023
  • Accept Date 05 February 2023