Decreased Follistatin Levels as a Risk of Acute Sarcopenia Marker in Elderly

I Gusti Putu Suka Aryana, I Made Arya Winangun


Background: Acute sarcopenia is an acute muscle loss that has been associated to the frailty and vulnerability of the elderly. Follistatin has been known as a significant marker for sarcopenia, however, studies of follistatin in humans have shown varying results and there have been no studies to date regarding the relationship between follistatin and acute sarcopenia. The aim of this study was to determine changes in follistatin levels as a risk of acute sarcopenia in elderly.

Materials and methods: This study was a prospective observational study involving hospitalized elderly. The follistatin level was examined with enzyme-linked immunosorbent assay (ELISA). Meanwhile the determination of acute sarcopenia was done through the measurement of changes in hand grip strength and calf circumference parameters. The data obtained was descriptively analyzed, followed by bivariate and multivariate analysis. A p<0.05 was considered significant.

Results: There were 66 subjects in this study. A total of 10 subjects (15.2%) had acute sarcopenia on the 7th day of hospitalization. The cut-off point of decreased follistatin levels was 4.870 with a sensitivity of 82.1% and a specificity of 60%. There was an association between decreased follistatin levels and acute sarcopenia (p=0.01; RR: 6.90; 95% CI: 1.638-29.069). Multivariate analysis results showed that decreased follistatin levels was a significant factor that might influence the occurrence of acute sarcopenia.

Conclusion: Since this study showed that decreased follistatin levels might be a risk of acute sarcopenia in the elderly, thus it could be used as a marker of acute sarcopenia, which should be further investigated.

Keywords: decreased follistatin levels, acute sarcopenia, elderly

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Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc. 2020; 21(3): 300-307.e2, CrossRef.

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing. 2019; 48(1): 16-31, CrossRef.

Welch C, Greig CA, Masud T, Pinkney T, Jackson TA. Protocol for understanding acute sarcopenia: A cohort study to characterise changes in muscle quantity and physical function in older adults following hospitalisation. BMC Geriatr. 2020; 20: 239, CrossRef.

Welch C, Greig CA, Hassan‑Smith ZK, Pinkney TD, Lord JM, Jackson TA. A pilot observational study measuring acute sarcopenia in older colorectal surgery patients. BMC Res Notes. 2019; 12: 24, CrossRef.

Martone AM, Bianchi L, Abete P, Bellelli G, Bo M, Cherubini A, et al. The incidence of sarcopenia among hospitalized older patients: Results from the Glisten study. J Cachexia Sarcopenia Muscle. 2017; 8(6): 907-14, CrossRef.

Hansen J, Brandt C, Nielsen AR, Hojman P, Whitham M, Febbraio MA, et al. Exercise induces a marked increase in plasma follistatin: Evidence that follistatin is a contraction-induced hepatokine. Endocrinology. 2011; 151(1): 164-71, CrossRef.

Pedersen BK, Febbraio MA. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012; 8(8): 457-65, CrossRef.

Han X, Møller LLV, De Groote E, Bojsen-Møller KN, Davey J, Henríquez-Olguin C, et al. Mechanisms involved in follistatin-induced hypertrophy and increased insulin action in skeletal muscle. J Cachexia Sarcopenia Muscle. 2019; 10(6): 1241-57, CrossRef.

Sepulveda PV, Lamon S, Hagg A, Thomson RE, Winbanks CE, Qian H, et al. Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy. Sci Rep. 2015; 5: 17535, CrossRef.

Yaden BC, Croy JE, Wang Y, Wilson JM, Datta-Mannan A, Shetler P, et al. Follistatin: A novel therapeutic for the improvement of muscle regenerations. J Pharmacol Exp Ther. 2014; 349(2): 355-71, CrossRef.

Oh KJ, Lee DS, Kim WK, Han BS, Lee SC, Bae KH. Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int J Mol Sci. 2017; 18(1): 8, CrossRef.

Fife E, Kostka J, Kroc L, Guligowska A, Pigłowska M, Soltysik B, et al. Relationship of muscle function to circulating myostatin, follistatin and GDF11 in older women and men. BMC Geriatr. 2018; 18: 200, CrossRef.

Hofmann M, Halper B, Oesen S, Franzke B, Stuparits P, Tschan H, et al. Serum concentrations of insulin-like growth factor-1, members of the TGF-beta superfamily and follistatin do not reflect different stages of dynapenia and sarcopenia in elderly women. Exp Gerontol. 2015; 64: 35-45, CrossRef.

Liaw FY, Kao TW, Fang WH, Han DS, Chi YC, Yang WS. Increased follistatin associated with decreased gait speed among old adults. Eur J Clin Invest. 2016; 46(4): 321-7, CrossRef.

Margutti KMM, Schuch NJ, Schwanke CHA. Inflammatory markers, sarcopenia and its diagnostic criteria among the elderly: A systematic review. Rev Bras Geriatr Gerontol. 2017; 20(3): 441-53, CrossRef.

Wall BT, Dirks ML, Snijders T, Senden JMG, Dolmans J, van Loon LJC. Substantial skeletal muscle loss occurs during only 5 days of disuse. Acta Physiol. 2014; 210(3): 600-11, CrossRef.

Welch C, Hassan-Smith ZK, Greig CA, Lord JM, Jackson TA. Acute sarcopenia secondary to hospitalisation – An emerging condition affecting older adults. Aging Dis. 2018; 9(1): 151-64, CrossRef.

Sousa AS, Guerra RS, Fonseca I, Pichel F, Amaral TF. Sarcopenia and length of hospital stay. Eur J Clin Nutr. 2015; 70(5): 595-601, CrossRef.

Wu YH, Hwang AC, Liu LK, Peng LN, Chen LK. Sex differences of sarcopenia in Asian populations: The implications in diagnosis and management. J Clin Gerontol Geriatr. 2016; 7(2): 37-43, CrossRef.

Rinnov AR, Plomgaard P, Pedersen BK, Gluud LL. Impaired follistatin secretion in cirrhosis. J Clin Endocrinol Metab. 2016; 101(9): 3395-400, CrossRef.

Mienche, Setiati S, Setyohadi B, Kurniawan J, Laksmi PW, Ariane A, et al. Diagnostic performance of calf circumference, thigh circumference, and SARC-F questionnaire to identify sarcopenia in elderly compared to Asian working group for sarcopenia’s diagnostic standard. Acta Med Indones. 2019; 51(2): 117-27, article.

Norton K. Standards for anthropometry assessment. In: Norton K, Eston R, editors. Kinanthropometry and Exercise Physiology. 4th ed. South Australia: Routledge; 2020. p.68-137, article.

De Spiegeleer A, Kahya H, Sanchez-Rodriguez D, Piotrowicz K, Surquin M, Marco E, et al. Acute sarcopenia changes following hospitalization: Influence of pre-admission care dependency level. Age Ageing. 2021; 50(6): 2140-6, CrossRef.

LeBlanc A, Gogia P, Schneider V, Krebs J, Schonfeld E, Evans H. Calf muscle area and strength changes after five weeks of horizontal bed rest. Am J Sports Med. 1988; 16(6): 624-9, CrossRef.

Santos LP, Gonzalez MC, Orlandi SP, Bielemann RM, Barbosa-Silva TG, Heymsfield SB, et al. New prediction equations to estimate appendicular skeletal muscle mass using calf circumference: Results from NHANES 1999–2006. J Parenter Enteral Nutr. 2019; 43(8): 998-1007, CrossRef.

Kawakami R, Miyachi M, Sawada SS, Torii S, Midorikawa T, Tanisawa K, et al. Cut-offs for calf circumference as a screening tool for low muscle mass: WASEDA’S Health Study. Geriatr Gerontol Int. 2020; 20(10): 943-950, CrossRef.

Kementerian Kesehatan Republik Indonesia. Peraturan Menteri Kesehatan Nomor 25 Tahun 2016 tentang Rencana Aksi Nasional Kesehatan Lanjut Usia Tahun 2016-2019. Jakarta: Kementerian Kesehatan Republik Indonesia; 2016, article.

Du Y, Xu C, Shi H, Jiang X, Tang W, Wu X, et al. Serum concentrations of oxytocin, DHEA and follistatin are associated with osteoporosis or sarcopenia in community-dwelling postmenopausal women. BMC Geriatr. 2021; 542: 21, CrossRef.

Sordi CM, Reis-Neto ET, Keppeke GD, Shinjo SK, Sato EI. Serum myostatin and follistatin levels in patients with dermatomyositis and polymyositis. J Clin Rheumatol. 2022; 28(1): 33-7, CrossRef.

Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, et al. A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mol Ther. 2015; 23(1): 192-201, CrossRef.

Aryana IGPS, Setiati S, Rini SS. Molecular mechanism of acute sarcopenia in elderly patient with COVID–19. Acta Med Indones. 2021; 53(4): 481-92, article.

Jürimäe J, Vaiksaar S, Purge P, Tillmann V. Irisin, fibroplast growth factor-21, and follistatin responses to endurance rowing training session in female rowers. Front Physiol. 2021; 12: 689696, CrossRef.

Domin R, Dadej D, Pytka M, Zybek-Kocik A, Ruchala M, Guzik P. Effect of various exercise regimens on selected exercise-induced cytokines in healthy people. Int J Environ Res Public Health. 2021; 18(3):1261, CrossRef.

Hansen JS, Rutti S, Arous C, Clemmesen JO, Secher NH, Drescher A, et al. Circulating follistatin is liver-derived and regulated by the glucagon-to-insulin ratio. J Clin Endocrinol Metab. 2016; 101(2): 550-60, CrossRef.

Gonzalez-Gil AM, Elizondo-Montemayor L. The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients. 2020; 12(6): 1899, CrossRef.

Hansen JS, Plomgaard P. Circulating follistatin in relation to energy metabolism. Mol Cell Endocrinol. 2016; 433: 87-93. doi: 10.1016/j.mce.2016.06.002, CrossRef.

Aryana IGPS, Hapsari AAAR, Kuswardhani RAT. Myokine regulation as marker of sarcopenia in elderly. Mol Cell Biomed Sci. 2018; 2(2): 38-47, CrossRef.


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