Sarcopenia: Molecular pathways and potential benefits of exercise training

Document Type : Review Articles

Authors

1 Department of Exercise Physiology, Islamic Azad University, Karaj Branch, Alborz, Iran.

2 department of exercise physiology , physical education & sport sciences faculty, Islamic Azad University Karaj branch, Alborz, Iran.

3 Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

4 Clinical Care and Health Promotion Research Center, Karaj branch, Islamic Azad University, Karaj, Iran.

5 Lviv State University of Physical Culture (Lviv, Ukraine), Department of Sports Medicine, Human Health.

Abstract

Sarcopenia, an age-associated phenomenon, is characterized by the reduced skeletal muscle mass and function. Research studies indicate that a wide range of factors can play a key role in the onset of muscle atrophy and its progression, especially during old age. However, the pathophysiology of this event is not well understood and there are many unresolved issues yet. Performing different training methods (aerobic, resistance, and concurrent) is among the strategies that may be beneficial for the prevention and improvement of sarcopenia by affecting the signaling pathways of muscle cells. On the other hand, the way in which this type of training affects the signaling pathways involved in sarcopenia has not been well understood. Even the previous research has been incapable of well introducing an effective training method for the elderly at risk for sarcopenia. Generally, in this review article, we investigate and summarize the important and key mechanisms that may contribute to sarcopenia. In the following, we have examined the effect of regular physical activity on cellular signaling pathways involved in sarcopenia, as well as the usefulness of aerobic, resistance, and concurrent activities in adaptation and prevention of the pathology of sarcopenia in the elderly.

What is already known on this subject?

Research studies indicate that a wide range of factors can play a key role in the onset of muscle atrophy and its progression, especially during old age.

 

What this study adds?

The obtained evidence shows that performing aerobic and resistance exercises is probably beneficial in prevention of sarcopenia in the elderly. However, the effectiveness and efficiency of concurrent exercises seems to be better for the elderly at risk for sarcopenia. 

Keywords

Main Subjects


Akune, T., Muraki, S., Oka, H., Tanaka, S., Kawaguchi, H., Nakamura, K., & Yoshimura, N. (2014). Exercise habits during middle age are associated with lower prevalence of sarcopenia: The ROAD study. Osteoporosis International, 25(3), 1081–1088. https://doi.org/10.1007/s00198-013-2550-z
Aoki, K., Konno, M., Honda, K., Abe, T., Nagata, T., Takehara, M., Sugasawa, T., Takekoshi, K., & Ohmori, H. (2020). Habitual Aerobic Exercise Diminishes the Effects of Sarcopenia in Senescence-Accelerated Mice Prone8 Model. Geriatrics (Basel, Switzerland), 5(3). https://doi.org/10.3390/geriatrics5030048
Bagheri, R., Moghadam, B. H., Church, D. D., Tinsley, G. M., Eskandari, M., Moghadam, B. H., Motevalli, M. S., Baker, J. S., Robergs, R. A., & Wong, A. (2020). The effects of concurrent training order on body composition and serum concentrations of follistatin, myostatin and GDF11 in sarcopenic elderly men. Experimental Gerontology, 133(October 2019), 110869. https://doi.org/10.1016/j.exger.2020.110869
Barajas-Galindo, D. E., González Arnáiz, E., Ferrero Vicente, P., & Ballesteros-Pomar, M. D. (2021). Effects of physical exercise in sarcopenia. A systematic review. Endocrinología, Diabetes y Nutrición (English Ed.), 68(3), 159–169. https://doi.org/10.1016/j.endien.2020.02.007
Barclay, R. D., Burd, N. A., Tyler, C., Tillin, N. A., & Mackenzie, R. W. (2019). The Role of the IGF-1 Signaling Cascade in Muscle Protein Synthesis and Anabolic Resistance in Aging Skeletal Muscle. Frontiers in Nutrition, 6(September), 1–9. https://doi.org/10.3389/fnut.2019.00146
Bartlett, J. D., Close, G. L., Drust, B., & Morton, J. P. (2014). The emerging role of p53 in exercise metabolism. Sports Medicine, 44(3), 303–309. https://doi.org/10.1007/s40279-013-0127-9
Beckwée, D., Delaere, A., Aelbrecht, S., Baert, V., Beaudart, C., Bruyere, O., de Saint-Hubert, M., & Bautmans, I. (2019). Exercise Interventions for the Prevention and Treatment of Sarcopenia. A Systematic Umbrella Review. Journal of Nutrition, Health and Aging, 23(6), 494–502. https://doi.org/10.1007/s12603-019-1196-8
Bengal, E., Aviram, S., & Hayek, T. (2020). P38 mapk in glucose metabolism of skeletal muscle: Beneficial or harmful? International Journal of Molecular Sciences, 21(18), 1–17. https://doi.org/10.3390/ijms21186480
Beyfuss, K., & Hood, D. A. (2018). A systematic review of p53 regulation of oxidative stress in skeletal muscle. Redox Report, 23(1), 100–117. https://doi.org/10.1080/13510002.2017.1416773
Bowlus, C. L. (2014). Chapter 34 - p53 Autoantibodies. In Y. Shoenfeld, P. L. Meroni, & M. E. Gershwin (Eds.), Autoantibodies (Third Edition) (Third Edition, pp. 289–294). Elsevier. https://doi.org/https://doi.org/10.1016/B978-0-444-56378-1.00034-4
Brightwell, C. R., Markofski, M. M., Moro, T., Fry, C. S., Porter, C., Volpi, E., & Rasmussen, B. B. (2019). Moderate‐intensity aerobic exercise improves skeletal muscle quality in older adults. Translational Sports Medicine, 2(3), 109–119. https://doi.org/10.1002/tsm2.70
Cadore, Eduardo L., & Izquierdo, M. (2013). New strategies for the concurrent strength-, power-, and endurance-training prescription in elderly individuals. Journal of the American Medical Directors Association, 14(8), 623–624. https://doi.org/10.1016/j.jamda.2013.04.008
Cadore, Eduardo L, Pinto, R. S., Pinto, S. S., Alberton, C. L., Correa, C. S., Tartaruga, M. P., Silva, E. M., Almeida, A. P. V, Trindade, G. T., & Kruel, L. F. M. (2011). Effects of strength, endurance, and concurrent training on aerobic power and dynamic  neuromuscular economy in elderly men. Journal of Strength and Conditioning Research, 25(3), 758–766. https://doi.org/10.1519/JSC.0b013e318207ed66
Cadore, Eduardo Lusa, & Izquierdo, M. (2019). Concurrent Training in Elderly. Concurrent Aerobic and Strength Training, 277–291. https://doi.org/10.1007/978-3-319-75547-2_18
Cadore, Eduardo Lusa, Pinto, R. S., Pinto, S. E., Lhullier, F. L. R., Correa, C. S., Alberton, C. L., Pinto, S. E., Almeida, A. P. V., Tartaruga, M. P., Silva, E. M., & Kruel, L. F. M. (2010). Physiological Effects of Concurrent Training in Elderly Men Physiological E ff ects of Concurrent Training in Elderly Men. International Journal of Sports Medicine, 689–697.
Cardoso, A. L., Fernandes, A., Aguilar-Pimentel, J. A., de Angelis, M. H., Guedes, J. R., Brito, M. A., Ortolano, S., Pani, G., Athanasopoulou, S., Gonos, E. S., Schosserer, M., Grillari, J., Peterson, P., Tuna, B. G., Dogan, S., Meyer, A., van Os, R., & Trendelenburg, A. U. (2018). Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases. Ageing Research Reviews, 47(April), 214–277. https://doi.org/10.1016/j.arr.2018.07.004
Chen, N., He, X., Zhao, G., Lu, L., Ainsworth, B. E., Liu, Y., & Wu, X. (2021). Efficacy of low-load resistance training combined with blood flow restriction vs. high-load resistance training on sarcopenia among community-dwelling older Chinese people: study protocol for a 3-arm randomized controlled trial. Trials, 22(1), 1–12. https://doi.org/10.1186/s13063-021-05495-z
Corazza, A. V., Paolillo, F. R., Groppo, F. C., Bagnato, V. S., & Caria, P. H. F. (2013). Phototherapy and resistance training prevent sarcopenia in ovariectomized rats. Lasers in Medical Science, 28(6), 1467–1474. https://doi.org/10.1007/s10103-012-1251-8
Cumming, K. T., Kvamme, N. H., Schaad, L., Ugelstad, I., & Raastad, T. (2021). Muscular HSP70 content is higher in elderly compared to young, but is normalized after 12 weeks of strength training. European Journal of Applied Physiology, 121(6), 1689–1699. https://doi.org/10.1007/s00421-021-04633-4
De Carvalho Cunha, V. N., Dos Santos Rosa, T., Sales, M. M., Sousa, C. V., Da Silva Aguiar, S., Deus, L. A., Simoes, H. G., & De Andrade, R. V. (2018). Training Performed above Lactate Threshold Decreases p53 and Shelterin Expression in Mice. International Journal of Sports Medicine, 39(9), 704–711. https://doi.org/10.1055/a-0631-3441
del Campo Cervantes, J. M., Macías Cervantes, M. H., & Monroy Torres, R. (2019). Effect of a Resistance Training Program on Sarcopenia and Functionality of the Older Adults Living in a Nursing Home. Journal of Nutrition, Health and Aging, 23(9), 829–836. https://doi.org/10.1007/s12603-019-1261-3
Delogu, W., Caligiuri, A., Provenzano, A., Rosso, C., Bugianesi, E., Coratti, A., Macias-Barragan, J., Galastri, S., Di Maira, G., & Marra, F. (2019). Myostatin regulates the fibrogenic phenotype of hepatic stellate cells via c-jun N-terminal kinase activation. Digestive and Liver Disease, 51(10), 1400–1408. https://doi.org/10.1016/j.dld.2019.03.002
Diaz-Ruiz, A., Gonzalez-Freire, M., Ferrucci, L., Bernier, M., & De Cabo, R. (2015). SIRT1 synchs satellite cell metabolism with stem cell fate. Cell Stem Cell, 16(2), 103–104. https://doi.org/10.1016/j.stem.2015.01.006
Dong, Z. J., Zhang, H. L., & Yin, L. X. (2019). Effects of intradialytic resistance exercise on systemic inflammation in maintenance hemodialysis patients with sarcopenia: a randomized controlled trial. International Urology and Nephrology, 51(8), 1415–1424. https://doi.org/10.1007/s11255-019-02200-7
Dubey, A., Prajapati, K. S., Swamy, M., & Pachauri, V. (2015). Heat shock proteins: A therapeutic target worth to consider. Veterinary World, 8(1), 46–51. https://doi.org/10.14202/vetworld.2015.46-51
Ebert, S. M., Dierdorff, J. M., Meyerholz, D. K., Bullard, S. A., Al-Zougbi, A., DeLau, A. D., Tomcheck, K. C., Skopec, Z. P., Marcotte, G. R., Bodine, S. C., & Adams, C. M. (2019). An investigation of p53 in skeletal muscle aging. Journal of Applied Physiology, 127(4), 1075–1084. https://doi.org/10.1152/japplphysiol.00363.2019
Ferat-Osorio, E., Sánchez-Anaya, A., Gutiérrez-Mendoza, M., Boscó-Gárate, I., Wong-Baeza, I., Pastelin-Palacios, R., Pedraza-Alva, G., Bonifaz, L. C., Cortés-Reynosa, P., Pérez-Salazar, E., Arriaga-Pizano, L., López-Macías, C., Rosenstein, Y., & Isibasi, A. (2014). Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/ constitutive heat shock element-binding factor-dependent mechanism. Journal of Inflammation (United Kingdom), 11(1), 1–12. https://doi.org/10.1186/1476-9255-11-19
Ferrari, R., Fuchs, S. C., Kruel, L. F. M., Cadore, E. L., Alberton, C. L., Pinto, R. S., Radaelli, R., Schoenell, M., Izquierdo, M., Tanaka, H., & Umpierre, D. (2016). Effects of different concurrent resistance and aerobic training frequencies on muscle power and muscle quality in trained elderly men: A randomized clinical trial. Aging and Disease, 7(6), 697–704. https://doi.org/10.14336/AD.2016.0504
Ferri, E., Marzetti, E., Calvani, R., Picca, A., Cesari, M., & Arosio, B. (2020). Role of age-related mitochondrial dysfunction in sarcopenia. International Journal of Molecular Sciences, 21(15), 1–12. https://doi.org/10.3390/ijms21155236
Folkesson, M., Mackey, A. L., Langberg, H., Oskarsson, E., Piehl-Aulin, K., Henriksson, J., & Kadi, F. (2013). The expression of heat shock protein in human skeletal muscle: Effects of muscle fibre phenotype and training background. Acta Physiologica, 209(1), 26–33. https://doi.org/10.1111/apha.12124
Gill, J. F., Santos, G., Schnyder, S., & Handschin, C. (2018). PGC-1α affects aging-related changes in muscle and motor function by modulating specific exercise-mediated changes in old mice. Aging Cell, 17(1), 1–13. https://doi.org/10.1111/acel.12697
Grutter Lopes, K., Alexandre Bottino, D., Farinatti, P., Coelho De Souza, M. das G., Alves Maranhão, P., De Araujo, C. M. S., Bouskela, E., Alves Lourenço, R., & De Oliveira, R. B. (2019). Strength training with blood flow restriction – a novel therapeutic approach for older adults with sarcopenia? A case report. Clinical Interventions in Aging, 14, 1461–1469. https://doi.org/10.2147/CIA.S206522
Harber, M. P., Konopka, A. R., Douglass, M. D., Minchev, K., Kaminsky, L. A., Trappe, T. A., & Trappe, S. (2009). Aerobic exercise training improves whole muscle and single myofiber size and function in older women. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 297(5), 1452–1459. https://doi.org/10.1152/ajpregu.00354.2009
Harber, M. P., Konopka, A. R., Undem, M. K., Hinkley, J. M., Minchev, K., Kaminsky, L. A., Trappe, T. A., & Trappe, S. (2012). Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent adaptations in myofiber function in young and older men. Journal of Applied Physiology, 113(9), 1495–1504. https://doi.org/10.1152/japplphysiol.00786.2012
Hirose, Y., Onishi, T., Miura, S., Hatazawa, Y., & Kamei, Y. (2018). Vitamin D attenuates FOXO1-target atrophy gene expression in C2C12 muscle cells. Journal of Nutritional Science and Vitaminology, 64(3), 229–232. https://doi.org/10.3177/jnsv.64.229
Hong, J., Kim, J., Kim, S. W., & Kong, H. J. (2017). Effects of home-based tele-exercise on sarcopenia among community-dwelling elderly adults: Body composition and functional fitness. Experimental Gerontology, 87, 33–39. https://doi.org/10.1016/j.exger.2016.11.002
Huang, S. W., Ku, J. W., Lin, L. F., Liao, C. De, Chou, L. C., & Liou, T. H. (2017). Body composition influenced by progressive elastic band resistance exercise of sarcopenic obesity elderly women: A pilot randomized controlled trial. European Journal of Physical and Rehabilitation Medicine, 53(4), 556–563. https://doi.org/10.23736/S1973-9087.17.04443-4
Iolascon, G., Di Pietro, G., Gimigliano, F., Mauro, G. L., Moretti, A., Giamattei, M. T., Ortolani, S., Tarantino, U., & Brandi, M. L. (2014). Physical exercise and sarcopenia in older people: Position paper of the Italian Society of Orthopaedics and Medicine (OrtoMed). Clinical Cases in Mineral and Bone Metabolism, 11(3), 215–221. https://doi.org/10.11138/ccmbm/2014.11.3.215
Izquierdo, M., Merchant, R. A., Morley, J. E., Anker, S. D., Aprahamian, I., Arai, H., Aubertin-Leheudre, M., Bernabei, R., Cadore, E. L., Cesari, M., Chen, L. K., de Souto Barreto, P., Duque, G., Ferrucci, L., Fielding, R. A., García-Hermoso, A., Gutiérrez-Robledo, L. M., Harridge, S. D. R., Kirk, B., … Singh, M. F. (2021). International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines. Journal of Nutrition, Health and Aging, 25(7), 824–853. https://doi.org/10.1007/s12603-021-1665-8
Ji, L. L., & Kang, C. (2015). Role of PGC-1α in sarcopenia: Etiology and potential intervention - A mini-review. Gerontology, 61(2), 139–148. https://doi.org/10.1159/000365947
Jung, S., Kim, S. H., Jeung, W., Ra, J., Heo, K., Shim, J. J., & Lee, J. L. (2021). Fermented antler improves endurance during exercise performance by increasing mitochondrial biogenesis and muscle strength in mice. Applied Sciences (Switzerland), 11(12). https://doi.org/10.3390/app11125386
Kang, C., & Ji, L. L. (2013). Role of PGC-1α in muscle function and aging. Journal of Sport and Health Science, 2(2), 81–86. https://doi.org/10.1016/j.jshs.2013.03.005
Karin, M., & Chang, L. (2001). Mammalian MAP kinase signaling cascades. Nature, 410(6824), 37–40.
Kim, H. J., Jung, K. J., Yu, B. P., Cho, C. G., & Chung, H. Y. (2002). Influence of aging and calorie restriction on MAPKs activity in rat kidney. Experimental Gerontology, 37(8–9), 1041–1053. https://doi.org/10.1016/S0531-5565(02)00082-7
Klotz, L. O., Sánchez-Ramos, C., Prieto-Arroyo, I., Urbánek, P., Steinbrenner, H., & Monsalve, M. (2015). Redox regulation of FoxO transcription factors. Redox Biology, 6, 51–72. https://doi.org/10.1016/j.redox.2015.06.019
Ko, Y. J., & Ko, I. G. (2021). Voluntary wheel running exercise improves aging-induced sarcopenia via activation of peroxisome proliferator-activated receptor gamma coactivator-1α/fibronectin type iii domain- containing protein 5/adenosine monophosphate-activated protein kinase signaling pathway. International Neurourology Journal, 25(Suppl 1), S27–S34. https://doi.org/10.5213/INJ.2142170.085
Koya, S., Kawaguchi, T., Hashida, R., Hirota, K., Bekki, M., Goto, E., Yamada, M., Sugimoto, M., Hayashi, S., Goshima, N., Yoshiyama, T., Otsuka, T., Nozoe, R., Nagamatsu, A., Nakano, D., Shirono, T., Shimose, S., Iwamoto, H., Niizeki, T., … Torimura, T. (2019). Effects of in-hospital exercise on sarcopenia in hepatoma patients who underwent transcatheter arterial chemoembolization. Journal of Gastroenterology and Hepatology (Australia), 34(3), 580–588. https://doi.org/10.1111/jgh.14538
Kramer, H. F., & Goodyear, L. J. (2007). Exercise, MAPK, and NF-κB signaling in skeletal muscle. Journal of Applied Physiology, 103(1), 388–395. https://doi.org/10.1152/japplphysiol.00085.2007
Krishnan, V. S., White, Z., Terrill, J. R., Hodgetts, S. I., Fitzgerald, M., Shavlakadze, T., Harvey, A. R., & Grounds, M. D. (2017). Resistance wheel exercise from mid-life has minimal effect on sciatic nerves from old mice in which sarcopenia was prevented. Biogerontology, 18(5), 769–790. https://doi.org/10.1007/s10522-017-9714-8
Laurin, J. L., Reid, J. J., Lawrence, M. M., & Miller, B. F. (2019). Long-term aerobic exercise preserves muscle mass and function with age. Current Opinion in Physiology, 10, 70–74. https://doi.org/10.1016/j.cophys.2019.04.019
Lavin, K. M., Roberts, B. M., Fry, C. S., Moro, T., Rasmussen, B. B., & Bamman, M. M. (2019). The importance of resistance exercise training to combat neuromuscular aging. Physiology, 34(2), 112–122. https://doi.org/10.1152/physiol.00044.2018
Léger, B., Cartoni, R., Praz, M., Lamon, S., Dériaz, O., Crettenand, A., Gobelet, C., Rohmer, P., Konzelmann, M., Luthi, F., & Russell, A. P. (2006). Akt signalling through GSK-3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. Journal of Physiology, 576(3), 923–933. https://doi.org/10.1113/jphysiol.2006.116715
Lessard, S. J., MacDonald, T. L., Pathak, P., Han, M. S., Coffey, V. G., Edge, J., Rivas, D. A., Hirshman, M. F., Davis, R. J., & Goodyear, L. J. (2018). JNK regulates muscle remodeling via myostatin/SMAD inhibition. Nature Communications, 9(1), 1–14. https://doi.org/10.1038/s41467-018-05439-3
Li, H., Malhotra, S., & Kumar, A. (2008). Nuclear factor-kappa B signaling in skeletal muscle atrophy. Journal of Molecular Medicine (Berlin, Germany), 86(10), 1113–1126. https://doi.org/10.1007/s00109-008-0373-8
Liang, J., Zhang, H., Zeng, Z., Wu, L., Zhang, Y., Guo, Y., Lv, J., Wang, C., Fan, J., & Chen, N. (2021a). Lifelong aerobic exercise alleviates sarcopenia by activating autophagy and inhibiting protein degradation via the ampk/pgc-1α signaling pathway. Metabolites, 11(5). https://doi.org/10.3390/metabo11050323
Liang, J., Zhang, H., Zeng, Z., Wu, L., Zhang, Y., Guo, Y., Lv, J., Wang, C., Fan, J., & Chen, N. (2021b). Lifelong Aerobic Exercise Alleviates Sarcopenia by Activating Autophagy and Inhibiting Protein Degradation via the AMPK/PGC-1α Signaling Pathway. Metabolites, 11(5). https://doi.org/10.3390/metabo11050323
Liang, Y., Wang, R., Jiang, J., Tan, L., & Yang, M. (2020). A randomized controlled trial of resistance and balance exercise for sarcopenic patients aged 80–99 years. Scientific Reports, 10(1), 1–7. https://doi.org/10.1038/s41598-020-75872-2
Liu, H. W., & Chang, S. J. (2018). Moderate exercise suppresses NF-κB signaling and activates the SIRT1-AMPK-PGC1α axis to attenuate muscle loss in diabetic db/db mice. Frontiers in Physiology, 9(MAY), 1–9. https://doi.org/10.3389/fphys.2018.00636
Liu, S., Yu, C., Xie, L., Niu, Y., & Fu, L. (2021). Aerobic Exercise Improves Mitochondrial Function in Sarcopenia Mice Through Sestrin2 in an AMPKα2-Dependent Manner. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 76(7), 1161–1168. https://doi.org/10.1093/gerona/glab029
Liu, Yuefei, Gampert, L., Nething, K., & Steinacker, J. M. (2006). Response and function of skeletal muscle heat shock protein 70. Frontiers in Bioscience: A Journal and Virtual Library, 11, 2802–2827. https://doi.org/10.2741/2011
Liu, Yusen, Shepherd, E. G., & Nelin, L. D. (2007). MAPK phosphatases - Regulating the immune response. Nature Reviews Immunology, 7(3), 202–212. https://doi.org/10.1038/nri2035
Lu, Y., Bradley, J. S., McCoski, S. R., Gonzalez, J. M., Ealy, A. D., & Johnson, S. E. (2017). Reduced skeletal muscle fiber size following caloric restriction is associated with calpain-mediated proteolysis and attenuation of IGF-1 signaling. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 312(5), R806–R815. https://doi.org/10.1152/ajpregu.00400.2016
Lustosa, L. P., & Gomes Pereira, D. A. (2014). Impact of Aerobic Training Associated with Muscle Strengthening in Elderly Individuals at Risk of Sarcopenia: A Clinical Trial. Journal of Gerontology and Griatric Research, 04(02), 10–13. https://doi.org/10.4172/2167-7182.1000208
Martins, R., Lithgow, G. J., & Link, W. (2016). Long live FOXO: Unraveling the role of FOXO proteins in aging and longevity. Aging Cell, 15(2), 196–207. https://doi.org/10.1111/acel.12427
Melouane, A., Yoshioka, M., & St-Amand, J. (2020). Extracellular matrix/mitochondria pathway: A novel potential target for sarcopenia. In Mitochondrion (Vol. 50). https://doi.org/10.1016/j.mito.2019.10.007
Mielgo-Ayuso, J., & Fernández-Lázaro, D. (2021). Sarcopenia, exercise and quality of life. International Journal of Environmental Research and Public Health, 18(10), 6–9. https://doi.org/10.3390/ijerph18105156
Milani, A., Basirnejad, M., & Bolhassani, A. (2019). Heat-shock proteins in diagnosis and treatment: An overview of different biochemical and immunological functions. Immunotherapy, 11(3), 215–239. https://doi.org/10.2217/imt-2018-0105
Miyabara, E. H., Nascimento, T. L., Rodrigues, D. C., Moriscot, A. S., Davila, W. F., AitMou, Y., DeTombe, P. P., & Mestril, R. (2012). Overexpression of inducible 70-kDa heat shock protein in mouse improves structural and functional recovery of skeletal muscles from atrophy. Pflugers Archiv European Journal of Physiology, 463(5), 733–741. https://doi.org/10.1007/s00424-012-1087-x
Moghadam, B. H., Bagheri, R., Ashtary-Larky, D., Tinsley, G. M., Eskandari, M., Wong, A., Moghadam, B. H., Kreider, R. B., & Baker, J. S. (2020). The Effects of Concurrent Training Order on Satellite Cell-Related Markers, Body Composition, Muscular and Cardiorespiratory Fitness in Older Men with Sarcopenia. The Journal of Nutrition, Health & Aging, 24(7), 796–804. https://doi.org/10.1007/s12603-020-1431-3
Morgan, M. J., & Liu, Z. G. (2011). Crosstalk of reactive oxygen species and NF-κB signaling. Cell Research, 21(1), 103–115. https://doi.org/10.1038/cr.2010.178
Myers, M. J., Shepherd, D. L., Durr, A. J., Stanton, D. S., Mohamed, J. S., Hollander, J. M., & Alway, S. E. (2019). The role of SIRT1 in skeletal muscle function and repair of older mice. Journal of Cachexia, Sarcopenia and Muscle, 10(4), 929–949. https://doi.org/10.1002/jcsm.12437
Nascimento, C. M., Ingles, M., Salvador-Pascual, A., Cominetti, M. R., Gomez-Cabrera, M. C., & Viña, J. (2019). Sarcopenia, frailty and their prevention by exercise. Free Radical Biology and Medicine, 132(August), 42–49. https://doi.org/10.1016/j.freeradbiomed.2018.08.035
Negaresh, R., Ranjbar, R., Baker, J. S., Habibi, A., Mokhtarzade, M., Gharibvand, M. M., & Fokin, A. (2019). Skeletal Muscle Hypertrophy, Insulin-like Growth Factor 1, Myostatin and Follistatin in Healthy and Sarcopenic Elderly Men: The Effect of Whole-body Resistance Training. International Journal of Preventive Medicine, 10, 29. https://doi.org/10.4103/ijpvm.IJPVM_310_17
Neves, L. X. da S., Teodoro, J. L., Menger, E., Lopez, P., Grazioli, R., Farinha, J., Moraes, K., Bottaro, M., Pinto, R. S., Izquierdo, M., & Cadore, E. L. (2018). Repetitions to failure versus not to failure during concurrent training in healthy elderly men: A randomized clinical trial. Experimental Gerontology, 108(March), 18–27. https://doi.org/10.1016/j.exger.2018.03.017
Njemini, R., Bautmans, I., Onyema, O. O., Van Puyvelde, K., Demanet, C., & Mets, T. (2011). Circulating Heat Shock Protein 70 in Health, Aging and Disease. BMC Immunology, 12, 13–15. https://doi.org/10.1186/1471-2172-12-24
Odeh, M., Tamir-Livne, Y., Haas, T., & Bengal, E. (2020). P38α MAPK coordinates the activities of several metabolic pathways that together induce atrophy of denervated muscles. FEBS Journal, 287(1), 73–93. https://doi.org/10.1111/febs.15070
Oliveira, A. N., & Hood, D. A. (2019). Exercise is mitochondrial medicine for muscle. Sports Medicine and Health Science, 1(1). https://doi.org/10.1016/j.smhs.2019.08.008
Parkington, J. D., LeBrasseur, N. K., Siebert, A. P., & Fielding, R. A. (2004). Contraction-mediated mTOR, p70S6k, and ERK1/2 phosphorylation in aged skeletal muscle. Journal of Applied Physiology (Bethesda, Md.: 1985), 97(1), 243–248. https://doi.org/10.1152/japplphysiol.01383.2003
Patel, H. P. (2017). Epidemiology of Sarcopenia and Frailty (E. Clift (ed.); p. Ch. 1). IntechOpen. https://doi.org/10.5772/intechopen.69771
Phu, S., Boersma, D., & Duque, G. (2015). Exercise and Sarcopenia. Journal of Clinical Densitometry, 18(4), 488–492. https://doi.org/10.1016/j.jocd.2015.04.011
Picca, A., Calvani, R., Bossola, M., Allocca, E., Menghi, A., Pesce, V., Lezza, A. M. S., Bernabei, R., Landi, F., & Marzetti, E. (2018). Update on mitochondria and muscle aging: All wrong roads lead to sarcopenia. In Biological Chemistry (Vol. 399, Issue 5). https://doi.org/10.1515/hsz-2017-0331
Plotnikov, A., Zehorai, E., Procaccia, S., & Seger, R. (2011). The MAPK cascades: Signaling components, nuclear roles and mechanisms of nuclear translocation. Biochimica et Biophysica Acta - Molecular Cell Research, 1813(9), 1619–1633. https://doi.org/10.1016/j.bbamcr.2010.12.012
Radak, Z., Suzuki, K., Posa, A., Petrovszky, Z., Koltai, E., & Boldogh, I. (2020). The systemic role of SIRT1 in exercise mediated adaptation. Redox Biology, 35(February), 101467. https://doi.org/10.1016/j.redox.2020.101467
Rahman, S., & Islam, R. (2011). Mammalian Sirt1: Insights on its biological functions. Cell Communication and Signaling, 9, 1–8. https://doi.org/10.1186/1478-811X-9-11
Ribeiro, M. B. T., Guzzoni, V., Hord, J. M., Lopes, G. N., Marqueti, R. D. C., De Andrade, R. V., Selistre-De-Araujo, H. S., & Durigan, J. L. Q. (2017). Resistance training regulates gene expression of molecules associated with intramyocellular lipids, glucose signaling and fiber size in old rats. Scientific Reports, 7(1), 1–13. https://doi.org/10.1038/s41598-017-09343-6
Rimer, M. (2020). Extracellular signal-regulated kinases 1 and 2 regulate neuromuscular junction and myofiber phenotypes in mammalian skeletal muscle. Neuroscience Letters, 715, 134671. https://doi.org/10.1016/j.neulet.2019.134671
Schumann, M., Feuerbacher, J. F., Sünkeler, M., Freitag, N., Rønnestad, B. R., Doma, K., & Lundberg, T. R. (2021). Compatibility of Concurrent Aerobic and Strength Training for Skeletal Muscle Size and Function: An Updated Systematic Review and Meta-Analysis. Sports Medicine. https://doi.org/10.1007/s40279-021-01587-7
Schwarzkopf, M., Coletti, D., & Marazzi, G. (2008). Chronic p53 activity leads to skeletal muscle atrophy and muscle stem cell perturbation. Basic Appl Myol, 18(5), 131–138. http://www.bio.unipd.it/bam/PDF/18-5/Schwarzkopf.pdf
Seaberg, B., Henslee, G., Wang, S., Paez-Colasante, X., Landreth, G. E., & Rimer, M. (2015). Muscle-Derived Extracellular Signal-Regulated Kinases 1 and 2 Are Required for the Maintenance of Adult Myofibers and Their Neuromuscular Junctions. Molecular and Cellular Biology, 35(7), 1238–1253. https://doi.org/10.1128/mcb.01071-14
Senf, S. M. (2013). Skeletal muscle heat shock protein 70: Diverse functions and therapeutic potential for wasting disorders. Frontiers in Physiology, 4 NOV(November), 1–6. https://doi.org/10.3389/fphys.2013.00330
Senf, S. M., Sandesara, P. B., Reed, S. A., & Judge, A. R. (2011). P300 acetyltransferase activity differentially regulates the localization and activity of the FOXO homologues in skeletal muscle. American Journal of Physiology - Cell Physiology, 300(6), 1490–1501. https://doi.org/10.1152/ajpcell.00255.2010
Seo, D. Y., & Hwang, B. G. (2020). Effects of exercise training on the biochemical pathways associated with sarcopenia. Physical Activity and Nutrition, 24(3), 32–38. https://doi.org/10.20463/pan.2020.0019
Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N., & Nair, K. S. (2004). Age and aerobic exercise training effects on whole body and muscle protein metabolism. American Journal of Physiology - Endocrinology and Metabolism, 286(1 49-1), 92–101. https://doi.org/10.1152/ajpendo.00366.2003
Silverstein, M. G., Ordanes, D., Wylie, A. T., Files, D. C., Milligan, C., Presley, T. D., & Kavanagh, K. (2014). Inducing muscle heat shock protein 70 improves insulin sensitivity and muscular performance in aged mice. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 70(7), 800–808. https://doi.org/10.1093/gerona/glu119
Siu, P. M., Pistilli, E. E., Murlasits, Z., & Alway, S. E. (2006). Hindlimb unloading increases muscle content of cytosolic but not nuclear Id2 and p53 proteins in young adult and aged rats. Journal of Applied Physiology, 100(3), 907–916. https://doi.org/10.1152/japplphysiol.01012.2005
Soares-Silva, M., Diniz, F. F., Gomes, G. N., & Bahia, D. (2016). The mitogen-activated protein kinase (MAPK) pathway: Role in immune evasion by trypanosomatids. Frontiers in Microbiology, 7(FEB), 1–9. https://doi.org/10.3389/fmicb.2016.00183
Takegaki, J., Sase, K., & Fujita, S. (2019). Repeated bouts of resistance exercise attenuate mitogen-activated protein-kinase signal responses in rat skeletal muscle. Biochemical and Biophysical Research Communications, 520(1), 73–78. https://doi.org/10.1016/j.bbrc.2019.09.050
Thoma, A., & Lightfoot, A. P. (2018). NF-kB and Inflammatory Cytokine Signalling: Role in Skeletal Muscle Atrophy. Advances in Experimental Medicine and Biology, 1088, 267–279. https://doi.org/10.1007/978-981-13-1435-3_12
Tilstra, J. S., Clauson, C. L., Niedernhofer, L. J., & Robbins, P. D. (2011). NF-κB in aging and disease. Aging and Disease, 2(6), 449–465.
Tournadre, A., Vial, G., Capel, F., Soubrier, M., & Boirie, Y. (2019). Sarcopenia. Joint Bone Spine, 86(3), 309–314. https://doi.org/10.1016/j.jbspin.2018.08.001
Vasconcelos, K. S. S., Dias, J. M. D., Araújo, M. C., Pinheiro, A. C., Moreira, B. S., & Dias, R. C. (2016). Effects of a progressive resistance exercise program with high-speed component on the physical function of older women with sarcopenic obesity: A randomized controlled trial. Brazilian Journal of Physical Therapy, 20(5), 432–440. https://doi.org/10.1590/bjpt-rbf.2014.0174
Veeranki, S., Lominadze, D., & Tyagi, S. C. (2015). Hyperhomocysteinemia inhibits satellite cell regenerative capacity through p38 alpha/beta MAPK signaling. American Journal of Physiology - Heart and Circulatory Physiology, 309(2), H325–H334. https://doi.org/10.1152/ajpheart.00099.2015
Vousden, K. H., & Lane, D. P. (2007). P53 in Health and Disease. Nature Reviews Molecular Cell Biology, 8(4), 275–283. https://doi.org/10.1038/nrm2147
White, Z., Terrill, J., White, R. B., McMahon, C., Sheard, P., Grounds, M. D., & Shavlakadze, T. (2016). Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice. Skeletal Muscle, 6(1), 1–21. https://doi.org/10.1186/s13395-016-0117-3
Williamson, D., Gallagher, P., Harber, M., Hollon, C., & Trappe, S. (2003). Mitogen-activated protein kinase (MAPK) pathway activation: Effects of age and acute exercise on human skeletal muscle. Journal of Physiology, 547(3), 977–987. https://doi.org/10.1113/jphysiol.2002.036673
Xie, Q., Chen, J., & Yuan, Z. (2012). Post-translational regulation of FOXO. Acta Biochimica et Biophysica Sinica, 44(11), 897–901. https://doi.org/10.1093/abbs/gms067
Yang, S., Loro, E., Wada, S., Kim, B., Tseng, W. J., Li, K., Khurana, T. S., & Arany, Z. (2020). Functional effects of muscle PGC-1alpha in aged animals. Skeletal Muscle, 10(1), 1–8. https://doi.org/10.1186/s13395-020-00231-8
Yin, L., Lu, L., Lin, X., & Wang, X. (2020). Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R-PI3K/Akt-mTOR pathway. Nutrition and Metabolism, 17(1), 1–10. https://doi.org/10.1186/s12986-020-00446-y
Yoo, S. Z., No, M. H., Heo, J. W., Park, D. H., Kang, J. H., Kim, S. H., & Kwak, H. B. (2018). Role of exercise in age-related sarcopenia. In Journal of Exercise Rehabilitation (Vol. 14, Issue 4). https://doi.org/10.12965/jer.1836268.134
Yoshida, T., & Delafontaine, P. (2020). Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy. Cells, 9(9), 1–25. https://doi.org/10.3390/cells9091970
Yuasa, K., Okubo, K., Yoda, M., Otsu, K., Ishii, Y., Nakamura, M., Itoh, Y., & Horiuchi, K. (2018). Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy. Scientific Reports, 8(1), 1–9. https://doi.org/10.1038/s41598-018-26632-w
Ziaaldini, M. M., Marzetti, E., Picca, A., & Murlasits, Z. (2017). Biochemical pathways of sarcopenia and their modulation by physical exercise: A narrative review. Frontiers in Medicine, 4(OCT). https://doi.org/10.3389/fmed.2017.00167