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Sarcopenia versus cancer cachexia: the muscle wasting continuum in healthy and diseased aging

Abstract

Muscle wasting is one of the major health problems in older adults and is traditionally associated to sarcopenia. Nonetheless, muscle loss may also occur in older adults in the presence of cancer, and in this case, it is associated to cancer cachexia. The clinical management of these conditions is a challenge due to, at least in part, the difficulties in their differential diagnosis. Thus, efforts have been made to better comprehend the pathogenesis of sarcopenia and cancer cachexia, envisioning the improvement of their clinical discrimination and treatment. To add insights on this topic, this review discusses the current knowledge on key molecular players underlying sarcopenia and cancer cachexia in a comparative perspective. Data retrieved from this analysis highlight that while sarcopenia is characterized by the atrophy of fast-twitch muscle fibers, in cancer cachexia an increase in the proportion of fast-twitch fibers appears to happen. The molecular drivers for these specificmuscle remodeling patterns are still unknown; however, among the predominant contributors to sarcopenia is the age-induced neuromuscular denervation, and in cancer cachexia, the muscle disuse experienced by cancer patients seems to play an important role. Moreover, inflammation appears to be more severe in cancer cachexia. Impairment of nutrition-related mediators may also contribute to sarcopenia and cancer cachexia, being distinctly modulated in each condition.

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References

  1. Aare S, Spendiff S, Vuda M et al (2016) Failed reinnervation in aging skeletal muscle. Skelet Muscle 6:29. https://doi.org/10.1186/s13395-016-0101-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Advani SM, Advani PG, VonVille HM, Jafri SH (2018) Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials. BMC Cancer 18:1174. https://doi.org/10.1186/s12885-018-5080-4

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Al-Majid S, McCarthy DO (2001) Resistance exercise training attenuates wasting of the extensor digitorum longus muscle in mice bearing the colon-26 adenocarcinoma. Biol Res Nurs 2:155–166. https://doi.org/10.1177/109980040100200301

    CAS  Article  PubMed  Google Scholar 

  4. Ali S, Garcia JM (2014) Sarcopenia, cachexia and aging: diagnosis, mechanisms and therapeutic options. Gerontology 60:294–305. https://doi.org/10.1159/000356760

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Antoun S, Raynard B (2018) Muscle protein anabolism in advanced cancer patients: response to protein and amino acids support, and to physical activity. Ann Oncol 29:ii10–ii17. https://doi.org/10.1093/annonc/mdx809

    CAS  Article  PubMed  Google Scholar 

  6. Aoyagi T, Terracina KP, Raza A et al (2015) Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol 7:17–29. https://doi.org/10.4251/wjgo.v7.i4.17

    Article  PubMed  PubMed Central  Google Scholar 

  7. Apel PJ, Alton T, Northam C et al (2009) How age impairs the response of the neuromuscular junction to nerve transection and repair: an experimental study in rats. J Orthop Res 27:385–393. https://doi.org/10.1002/jor.20773

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Arends J, Bachmann P, Baracos V et al (2017) ESPEN guidelines on nutrition in cancer patients. Clin Nutr 36:11–48. https://doi.org/10.1016/j.clnu.2016.07.015

    Article  PubMed  Google Scholar 

  9. Argilés JM (2005) Cancer-associated malnutrition. Eur J Oncol Nurs 9:S39–S50. https://doi.org/10.1016/j.ejon.2005.09.006

    Article  PubMed  Google Scholar 

  10. Argilés JM, Betancourt A, Guàrdia-Olmos J et al (2017) Validation of the CAchexia SCOre (CASCO). Staging cancer patients: the use of miniCASCO as a simplified tool. Front Physiol. https://doi.org/10.3389/fphys.2017.00092

    Article  PubMed  PubMed Central  Google Scholar 

  11. Argilés JM, Busquets S, López-Soriano FJ et al (2012) Are there any benefits of exercise training in cancer cachexia? J Cachexia Sarcopenia Muscle 3:73–76. https://doi.org/10.1007/s13539-012-0067-5

    Article  PubMed  PubMed Central  Google Scholar 

  12. Argilés JM, Busquets S, Moore-Carrasco R, López-Soriano FJ (2006) The role of cytokines in cancer cachexia. In: Mantovani G, Anker SD, Inui A et al (eds) Cachexia and wasting: a modern approach. Springer, Milano, pp 467–475

    Chapter  Google Scholar 

  13. Argilés JM, López-Soriano FJ, Stemmler B, Busquets S (2019) Therapeutic strategies against cancer cachexia. Eur J Transl Myol 29:4–13. https://doi.org/10.4081/ejtm.2019.7960

    Article  Google Scholar 

  14. Ascenzi F, Barberi L, Dobrowolny G et al (2019) Effects of IGF-1 isoforms on muscle growth and sarcopenia. Aging Cell 18:e12954. https://doi.org/10.1111/acel.12954

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Azeemuddin MM, Rao CM, Rafiq M et al (2019) Pharmacological investigation of ‘HIM-CHX’: a herbal combination in the experimental muscle wasting condition. Exp Gerontol 125:110663. https://doi.org/10.1016/j.exger.2019.110663

    CAS  Article  PubMed  Google Scholar 

  16. Baar MP, Perdiguero E, Muñoz-Cánoves P, de Keizer PL (2018) Musculoskeletal senescence: a moving target ready to be eliminated. Curr Opin Pharmacol 40:147–155. https://doi.org/10.1016/j.coph.2018.05.007

    CAS  Article  PubMed  Google Scholar 

  17. Bae T, Jang J, Lee H et al (2020) Paeonia lactiflora root extract suppresses cancer cachexia by down-regulating muscular NF-κB signalling and muscle-specific E3 ubiquitin ligases in cancer-bearing mice. J Ethnopharmacol 246:112222. https://doi.org/10.1016/j.jep.2019.112222

    CAS  Article  PubMed  Google Scholar 

  18. Baguet A, Everaert I, Hespel P et al (2011) A new method for non-invasive estimation of human muscle fiber type composition. PLoS One 6:e21956. https://doi.org/10.1371/journal.pone.0021956

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Baracos VE, Martin L, Korc M et al (2018) Cancer-associated cachexia. Nat Rev Dis Prim 4:17105. https://doi.org/10.1038/nrdp.2017.105

    Article  PubMed  Google Scholar 

  20. Baspinar S, Bircan S, Ciris M et al (2017) Expression of NGF, GDNF and MMP-9 in prostate carcinoma. Pathol Res Pract 213:483–489. https://doi.org/10.1016/j.prp.2017.02.007

    CAS  Article  PubMed  Google Scholar 

  21. Bassel-Duby R, Olson EN (2006) Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem 75:19–37. https://doi.org/10.1146/annurev.biochem.75.103004.142622

    CAS  Article  PubMed  Google Scholar 

  22. Bauer J, Biolo G, Cederholm T et al (2013) Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE study group. J Am Med Dir Assoc 14:542–559. https://doi.org/10.1016/j.jamda.2013.05.021

    Article  PubMed  Google Scholar 

  23. Becker C, Lord SR, Studenski SA et al (2015) Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol 3:948–957. https://doi.org/10.1016/S2213-8587(15)00298-3

    CAS  Article  PubMed  Google Scholar 

  24. Beckwée D, Delaere A, Aelbrecht S et al (2019) Exercise interventions for the prevention and treatment of sarcopenia. A systematic umbrella review. J Nutr Heal Aging 23:494–502. https://doi.org/10.1007/s12603-019-1196-8

    Article  Google Scholar 

  25. Bergen IIIHR, Farr JN, Vanderboom PM et al (2015) Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay. Skelet Muscle. https://doi.org/10.1186/s13395-015-0047-5

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bilir C, Engin H, Can M et al (2015) The prognostic role of inflammation and hormones in patients with metastatic cancer with cachexia. Med Oncol 32:56. https://doi.org/10.1007/s12032-015-0497-y

    CAS  Article  PubMed  Google Scholar 

  27. Bing C, Taylor S, Tisdale MJ, Williams G (2001) Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y. J Neurochem 79:1004–1012. https://doi.org/10.1046/j.1471-4159.2001.00639.x

    CAS  Article  PubMed  Google Scholar 

  28. Bloom I, Shand C, Cooper C et al (2018) Diet quality and sarcopenia in older adults: a systematic review. Nutrients 10:308. https://doi.org/10.3390/nu10030308

    Article  PubMed Central  Google Scholar 

  29. Boehm I, Miller J, Wishart TM et al (2020) Neuromuscular junctions are stable in patients with cancer cachexia. J Clin Invest 130:1461–1465. https://doi.org/10.1172/JCI128411

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Borras C, Ingles M, Mas-Bargues C et al (2020) Centenarians: an excellent example of resilience for successful ageing. Mech Ageing Dev 186:111199. https://doi.org/10.1016/j.mad.2019.111199

    CAS  Article  PubMed  Google Scholar 

  31. Botelho M, Cavadas C (2015) Neuropeptide Y: an anti-aging player? Trends Neurosci 38:701–711. https://doi.org/10.1016/j.tins.2015.08.012

    CAS  Article  PubMed  Google Scholar 

  32. Bowen TS, Schuler G, Adams V (2015) Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle 6:197–207. https://doi.org/10.1002/jcsm.12043

    Article  PubMed  PubMed Central  Google Scholar 

  33. Brocca L, Cannavino J, Coletto L et al (2012) The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms. J Physiol 590:5211–5230. https://doi.org/10.1113/jphysiol.2012.240267

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Brown JL, Lee DE, Rosa-Caldwell ME et al (2018) Protein imbalance in the development of skeletal muscle wasting in tumour-bearing mice. J Cachexia Sarcopenia Muscle 9:987–1002. https://doi.org/10.1002/jcsm.12354

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bye A, Wesseltoft-Rao N, Iversen PO et al (2016) Alterations in inflammatory biomarkers and energy intake in cancer cachexia: a prospective study in patients with inoperable pancreatic cancer. Med Oncol 33:54. https://doi.org/10.1007/s12032-016-0768-2

    CAS  Article  PubMed  Google Scholar 

  36. Callahan DM, Tourville TW, Miller MS et al (2015) Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function. Am J Physiol - Cell Physiol 308:C932–C943. https://doi.org/10.1152/ajpcell.00014.2015

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Campbell WW, Trappe TA, Wolfe RR, Evans WJ (2001) The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. J Gerontol - Ser A Biol Sci Med Sci 56A:M373–M380. https://doi.org/10.1093/gerona/56.6.m373

    CAS  Article  Google Scholar 

  38. Carlson BM, Dedkov EI, Borisov AB, Faulkner JA (2001) Skeletal muscle regeneration in very old rats. Journals Gerontol - Ser A Biol Sci Med Sci 56A:224–233. https://doi.org/10.1093/gerona/56.5.b224

    Article  Google Scholar 

  39. Carnac G, Vernus B, Bonnieu A (2007) Myostatin in the pathophysiology of skeletal muscle. Curr Genomics 8:415–422. https://doi.org/10.2174/138920207783591672

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Carosio S, Berardinelli MG, Aucello M, Musarò A (2011) Impact of ageing on muscle cell regeneration. Ageing Res Rev 10:35–42. https://doi.org/10.1016/j.arr.2009.08.001

    CAS  Article  PubMed  Google Scholar 

  41. Cella PS, Marinello PC, Borges FH et al (2019) Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling. Eur J Nutr. https://doi.org/10.1007/s00394-019-01933-6

    Article  PubMed  Google Scholar 

  42. Cerri AP, Bellelli G, Mazzone A et al (2015) Sarcopenia and malnutrition in acutely ill hospitalized elderly: prevalence and outcomes. Clin Nutr 34:745–751. https://doi.org/10.1016/j.clnu.2014.08.015

    Article  PubMed  Google Scholar 

  43. Chan R, Leung J, Woo J (2016) A prospective cohort study to examine the association between dietary patterns and sarcopenia in chinese community-dwelling older people in Hong Kong. J Am Med Dir Assoc 17:336–342. https://doi.org/10.1016/j.jamda.2015.12.004

    Article  PubMed  Google Scholar 

  44. Chance WT, Balasubramaniam A, Dayal R et al (1994) Hypothalamic concentration and release of neuropeptide Y into microdialysates is reduced in anorectic tumor-bearing rats. Life Sci 54:1869–1874. https://doi.org/10.1016/0024-3205(94)90144-9

    CAS  Article  PubMed  Google Scholar 

  45. Chance WT, Balasubramaniam A, Thompson H et al (1996) Assessment of feeding response of tumor-bearing rats to hypothalamic injection and infusion of neuropeptide Y. Peptides 17:797–801. https://doi.org/10.1016/0196-9781(96)00108-8

    CAS  Article  PubMed  Google Scholar 

  46. Chance WT, van Lammeren FM, Chen MH et al (1984) Plasma and brain cholecystokinin. J Surg Res 36:490–498. https://doi.org/10.1016/0022-4804(84)90131-8

    CAS  Article  PubMed  Google Scholar 

  47. Chatindiara I, Sheridan N, Kruger M, Wham C (2020) Eating less the logical thing to do? Vulnerability to malnutrition with advancing age: a qualitative study. Appetite 146:104502. https://doi.org/10.1016/j.appet.2019.104502

    Article  PubMed  Google Scholar 

  48. Chiodera P, Volpi R, Pilla S et al (2000) Decline in circulating neuropeptide Y levels in normal elderly human subjects. Eur J Endocrinol 143:715–716. https://doi.org/10.1530/eje.0.1430715

    CAS  Article  PubMed  Google Scholar 

  49. Cho Y, Kim JW, Keum KC et al (2018) Prognostic significance of sarcopenia with inflammation in patients with head and neck cancer who underwent definitive chemoradiotherapy. Front Oncol. https://doi.org/10.3389/fonc.2018.00457

    Article  PubMed  PubMed Central  Google Scholar 

  50. Cole CL, Kleckner IR, Jatoi A et al (2018) The role of systemic inflammation in cancer-associated muscle wasting and rationale for exercise as a therapeutic intervention. JCSM Clin Reports 3:e00065

    Article  Google Scholar 

  51. Coppola JD, Horwitz BA, Hamilton J, McDonald RB (2004) Expression of NPY Y1 and Y5 receptors in the hypothalamic paraventricular nucleus of aged Fischer 344 rats. Am J Physiol - Regul Integr Comp Physiol 287:R69–R75. https://doi.org/10.1152/ajpregu.00607.2003

    CAS  Article  PubMed  Google Scholar 

  52. Covault J, Sanes JR (1985) Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralyzed skeletal muscles. Proc Natl Acad Sci U S A 82:4544–4548. https://doi.org/10.1073/pnas.82.13.4544

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. Cox NJ, Ibrahim K, Sayer AA et al (2019) Assessment and treatment of the anorexia of aging: a systematic review. Nutrients 11:144. https://doi.org/10.3390/nu11010144

    CAS  Article  PubMed Central  Google Scholar 

  54. Cruz-Jentoft AJ, Bahat G, Bauer J et al (2019) Sarcopenia: revised european consensus on definition and diagnosis. Age Ageing 48:16–31. https://doi.org/10.1093/ageing/afy169

    Article  PubMed  Google Scholar 

  55. Dalle S, Rossmeislova L, Koppo K (2017) The role of inflammation in age-related sarcopenia. Front Physiol. https://doi.org/10.3389/fphys.2017.01045

    Article  PubMed  PubMed Central  Google Scholar 

  56. Daou N, Hassani M, Matos E et al (2020) Displaced myonuclei in cancer cachexia suggest altered innervation. Int J Mol Sci 21:1092. https://doi.org/10.3390/ijms21031092

    CAS  Article  PubMed Central  Google Scholar 

  57. de Castro GS, Correia-Lima J, Simoes E et al (2020) Myokines in treatment-naïve patients with cancer-associated cachexia. Clin Nutr. https://doi.org/10.1016/j.clnu.2020.10.050

    Article  PubMed  Google Scholar 

  58. Degens H, Alway SE (2006) Control of muscle size during disuse, disease, and aging. Int J Sports Med 27:94–99. https://doi.org/10.1055/s-2005-837571

    CAS  Article  PubMed  Google Scholar 

  59. Desgeorges MM, Devillard X, Toutain J et al (2017) Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke. Sci Rep. https://doi.org/10.1038/s41598-017-13912-0

    Article  PubMed  PubMed Central  Google Scholar 

  60. Deutz NEP, Ashurst I, Ballesteros MD et al (2019) The underappreciated role of low muscle mass in the management of malnutrition. J Am Med Dir Assoc 20:22–27. https://doi.org/10.1016/j.jamda.2018.11.021

    Article  PubMed  Google Scholar 

  61. Di Francesco V, Zamboni M, Dioli A et al (2005) Delayed postprandial gastric emptying and impaired gallbladder contraction together with elevated cholecystokinin and peptide YY serum levels sustain satiety and inhibit hunger in healthy elderly persons. J Gerontol - Ser A Biol Sci Med Sci 60A:1581–1585. https://doi.org/10.1093/gerona/60.12.1581

    Article  Google Scholar 

  62. Diffee GM, Kalfas K, Al-Majid S, McCarthy DO (2002) Altered expression of skeletal muscle myosin isoforms in cancer cachexia. Am J Physiol - Cell Physiol 283:C1376–C1382. https://doi.org/10.1152/ajpcell.00154.2002

    CAS  Article  PubMed  Google Scholar 

  63. Dunne RF, Loh KP, Williams GR et al (2019) Cachexia and sarcopenia in older adults with cancer: a comprehensive review. Cancers (Basel) 11:1861. https://doi.org/10.3390/cancers11121861

    Article  Google Scholar 

  64. Ebner N, Anker SD, von Haehling S (2019) Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 11th Cachexia conference. J Cachexia Sarcopenia Muscle 10:218–225. https://doi.org/10.1002/jcsm.12408

    Article  PubMed  PubMed Central  Google Scholar 

  65. Elliott B, Renshaw D, Getting S, Mackenzie R (2012) The central role of myostatin in skeletal muscle and whole body homeostasis. Acta Physiol 205:324–340. https://doi.org/10.1111/j.1748-1716.2012.02423.x

    CAS  Article  Google Scholar 

  66. Ezeoke CC, Morley JE (2015) Pathophysiology of anorexia in the cancer cachexia syndrome. J Cachexia Sarcopenia Muscle 6:287–302. https://doi.org/10.1002/jcsm.12059

    Article  PubMed  PubMed Central  Google Scholar 

  67. Fearon K, Strasser F, Anker SD et al (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12:489–495. https://doi.org/10.1016/S1470-2045(10)70218-7

    Article  PubMed  Google Scholar 

  68. Fialka-Moser V, Crevenna R, Korpan M, Quittan M (2003) Cancer rehabilitation. Particularly with aspects on physical impairments. J Rehabil Med 35:153–162. https://doi.org/10.1080/16501970310000511

    Article  PubMed  Google Scholar 

  69. Fischer CP (2006) Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 12:6–33

    PubMed  Google Scholar 

  70. Fontes-Oliveira CC, Busquets S, Toledo M et al (2013) Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: altered energetic efficiency? Biochim Biophys Acta 1830:2770–2778. https://doi.org/10.1016/j.bbagen.2012.11.009

    CAS  Article  PubMed  Google Scholar 

  71. Garcia JM, Garcia-Touza M, Hijazi RA et al (2005) Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab 90:2920–2926. https://doi.org/10.1210/jc.2004-1788

    CAS  Article  PubMed  Google Scholar 

  72. Gibson JNA, Halliday D, Morrison WL et al (1987) Decrease in human quadriceps muscle protein turnover consequent upon leg immobilization. Clin Sci 72:503–509. https://doi.org/10.1042/cs0720503

    CAS  Article  Google Scholar 

  73. Gillon A, Sheard P (2015) Elderly mouse skeletal muscle fibres have a diminished capacity to upregulate NCAM production in response to denervation. Biogerontology 16:811–823. https://doi.org/10.1007/s10522-015-9608-6

    CAS  Article  PubMed  Google Scholar 

  74. Gleeson M, Bishop NC, Stensel DJ et al (2011) The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11:607–610. https://doi.org/10.1038/nri3041

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. Gomes M, Figueiredo D, Teixeira L et al (2017) Physical inactivity among older adults across Europe based on the SHARE database. Age Ageing 46:71–77. https://doi.org/10.1093/ageing/afw165

    Article  PubMed  Google Scholar 

  76. Greising SM, Ermilov LG, Sieck GC, Mantilla CB (2015) Ageing and neurotrophic signalling effects on diaphragm neuromuscular function. J Physiol 593:431–440. https://doi.org/10.1113/jphysiol.2014.282244

    CAS  Article  PubMed  Google Scholar 

  77. Guttridge DC, Mayo MW, Madrid LV et al (2000) NF-κB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 289:2363–2366. https://doi.org/10.1126/science.289.5488.2363

    CAS  Article  PubMed  Google Scholar 

  78. Ham DJ, Börsch A, Lin S et al (2020) The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia. Nat Commun 11:4510. https://doi.org/10.1038/s41467-020-18140-1

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. Han Y-Q, Ming S-L, Wu H-T et al (2018) Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation. Redox Biol 19:412–428. https://doi.org/10.1016/j.redox.2018.09.009

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  80. Hardee JP, Counts BR, Carson JA (2019) Understanding the role of exercise in cancer cachexia therapy. Am J Lifestyle Med 13:46–60. https://doi.org/10.1177/1559827617725283

    Article  PubMed  Google Scholar 

  81. Hardee JP, Lynch GS (2019) Current pharmacotherapies for sarcopenia. Expert Opin Pharmacother 20:1645–1657. https://doi.org/10.1080/14656566.2019.1622093

    CAS  Article  PubMed  Google Scholar 

  82. Hayot M, Michaud A, Koechlin C et al (2005) Skeletal muscle microbiopsy: a validation study of a minimally invasive technique. Eur Respir J 25:431–440. https://doi.org/10.1183/09031936.05.00053404

    CAS  Article  PubMed  Google Scholar 

  83. Hepple RT, Rice CL (2016a) Innervation and neuromuscular control in ageing skeletal muscle. J Physiol 594:1965–1978. https://doi.org/10.1113/JP270561

    CAS  Article  PubMed  Google Scholar 

  84. Hepple RT, Rice CL (2016b) Innervation and neuromuscular control in ageing skeletal muscle. J Physiol 594:1965–1978. https://doi.org/10.1113/JP270561

    CAS  Article  PubMed  Google Scholar 

  85. Heywood R, McCarthy AL, Skinner TL (2018) Efficacy of exercise interventions in patients with advanced cancer: a systematic review. Arch Phys Med Rehabil 99:2595–2620. https://doi.org/10.1016/j.apmr.2018.04.008

    Article  PubMed  Google Scholar 

  86. Hida T, Imagama S, Ando K et al (2018) Sarcopenia and physical function are associated with inflammation and arteriosclerosis in community-dwelling people: the Yakumo study. Mod Rheumatol 28:345–350. https://doi.org/10.1080/14397595.2017.1349058

    CAS  Article  PubMed  Google Scholar 

  87. Hope K, Ferguson M, Reidlinger DP, Agarwal E (2017) “I don’t eat when I’m sick”: older people’s food and mealtime experiences in hospital. Maturitas 97:6–13. https://doi.org/10.1016/j.maturitas.2016.12.001

    Article  PubMed  Google Scholar 

  88. Hou Y-C, Wang C-J, Chao Y-J et al (2018) Elevated serum interleukin-8 level correlates with cancer-related cachexia and sarcopenia: an indicator for pancreatic cancer outcomes. J Clin Med 7:502. https://doi.org/10.3390/jcm7120502

    Article  PubMed Central  Google Scholar 

  89. Isidori AM, Strollo F, Morè M et al (2000) Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab 85:1954–1962. https://doi.org/10.1210/jcem.85.5.6572

    CAS  Article  PubMed  Google Scholar 

  90. Janssen HCJP, Samson MM, Verhaar HJJ (2002) Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 75:611–615. https://doi.org/10.1093/ajcn/75.4.611

    CAS  Article  PubMed  Google Scholar 

  91. Jaul E, Barron J (2017) Age-related diseases and clinical and public health implications for the 85 years old and over population. Front Public Heal 5:335. https://doi.org/10.3389/fpubh.2017.00335

    Article  Google Scholar 

  92. Joanisse S, Nederveen JP, Snijders T et al (2016) Skeletal muscle regeneration, repair and remodelling in aging: the importance of muscle stem cells and vascularization. Gerontology 63:91–100. https://doi.org/10.1159/000450922

    Article  PubMed  Google Scholar 

  93. Johns N, Hatakeyama S, Stephens NA et al (2014) Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle. PLoS One 9:e83618. https://doi.org/10.1371/journal.pone.0083618

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  94. Joyce NC, Oskarsson B, Jin L (2015) Muscle biopsy evaluation in neuromuscular disorders. Phys Med Rehabil Clin N Am 23:609–631. https://doi.org/10.1016/j.pmr.2012.06.006

    Article  Google Scholar 

  95. Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol 18:621–663. https://doi.org/10.1146/annurev.immunol.18.1.621

    CAS  Article  PubMed  Google Scholar 

  96. Katsanos CS, Kobayashi H, Sheffield-Moore M et al (2006) A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol - Endocrinol Metab 291:E381–E387. https://doi.org/10.1152/ajpendo.00488.2005

    CAS  Article  PubMed  Google Scholar 

  97. Khatib MN, Shankar AH, Kirubakaran R et al (2018) Ghrelin for the management of cachexia associated with cancer. Cochrane Database Syst Rev CD012229. https://doi.org/10.1002/14651858.CD012229

    Article  Google Scholar 

  98. Kim HO, Kim H-S, Youn J-C et al (2011) Serum cytokine profiles in healthy young and elderly population assessed using multiplexed bead-based immunoassays. J Transl Med 9:113. https://doi.org/10.1186/1479-5876-9-113

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  99. Kitagawa M, Haji S, Amagai T (2017) Elevated serum AA/EPA ratio as a predictor of skeletal muscle depletion in cachexic patients with advanced gastro-intestinal cancers. In Vivo (Brooklyn) 31:1003–1009. https://doi.org/10.21873/invivo.11161

    CAS  Article  Google Scholar 

  100. Kortebein P, Symons TB, Ferrando A et al (2008) Functional impact of 10 days of bed rest in healthy older adults. Journals Gerontol - Ser A Biol Sci Med Sci 63A:1076–1081. https://doi.org/10.1093/gerona/63.10.1076

    Article  Google Scholar 

  101. Kuo IY, Ehrlich BE (2015) Signaling in muscle contraction. Cold Spring Harb Perspect Biol 7:a006023. https://doi.org/10.1101/cshperspect.a006023

    Article  PubMed  PubMed Central  Google Scholar 

  102. Kweder H, Eidi H (2018) Vitamin D deficiency in elderly: risk factors and drugs impact on vitamin D status. Avicenna J Med 8:139–146. https://doi.org/10.4103/ajm.AJM_20_18

    Article  PubMed  PubMed Central  Google Scholar 

  103. Kwon YN, Yoon SS (2017) Sarcopenia: neurological point of view. J Bone Metab 24:83–89. https://doi.org/10.11005/jbm.2017.24.2.83

    Article  PubMed  PubMed Central  Google Scholar 

  104. Landi F, Marzetti E, Liperoti R et al (2013) Nonsteroidal anti-inflammatory drug (NSAID) use and sarcopenia in older people: results from the ilSIRENTE study. J Am Med Dir Assoc 14:626e9-626e13. https://doi.org/10.1016/j.jamda.2013.04.012

    Article  Google Scholar 

  105. LeBrasseur NK, Schelhorn TM, Bernardo BL et al (2009) Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice. J Gerontol - Ser A Biol Sci Med Sci 64A:940–948. https://doi.org/10.1093/gerona/glp068

    CAS  Article  Google Scholar 

  106. Li C, Yu K, Shyh-Chang N et al (2019) Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia Sarcopenia Muscle 10:586–600. https://doi.org/10.1002/jcsm.12417

    Article  PubMed  PubMed Central  Google Scholar 

  107. Li J, Ito M, Ohkawara B et al (2018) Differential effects of spinal motor neuron-derived and skeletal muscle-derived Rspo2 on acetylcholine receptor clustering at the neuromuscular junction. Sci Rep. https://doi.org/10.1038/s41598-018-31949-7

    Article  PubMed  PubMed Central  Google Scholar 

  108. Li M, Larsson L (2010) Force-generating capacity of human myosin isoforms extracted from single muscle fibre segments. J Physiol 588:5105–5114. https://doi.org/10.1113/jphysiol.2010.199067

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  109. Lima JDCC, Simoes E, de Castro G et al (2019) Tumour-derived transforming growth factor-β signalling contributes to fibrosis in patients with cancer cachexia. J Cachexia Sarcopenia Muscle. https://doi.org/10.1002/jcsm.12441

    Article  PubMed  PubMed Central  Google Scholar 

  110. Litterini AJ, Fieler VK, Cavanaugh JT, Lee JQ (2013) Differential effects of cardiovascular and resistance exercise on functional mobility in individuals with advanced cancer: a randomized trial. Arch Phys Med Rehabil 94:2329–2335. https://doi.org/10.1016/j.apmr.2013.06.008

    Article  PubMed  Google Scholar 

  111. Liu D, Qiao X, Ge Z et al (2019) IMB0901 inhibits muscle atrophy induced by cancer cachexia through MSTN signaling pathway. Skelet Muscle. https://doi.org/10.1186/s13395-019-0193-2

    Article  PubMed  PubMed Central  Google Scholar 

  112. Loumaye A, de Barsy M, Nachit M et al (2015) Role of activin A and myostatin in human cancer cachexia. J Clin Endocrinol Metab 100:2030–2038. https://doi.org/10.1210/jc.2014-4318

    CAS  Article  PubMed  Google Scholar 

  113. Loumaye A, de Barsy M, Nachit M et al (2017) Circulating activin A predicts survival in cancer patients. J Cachexia Sarcopenia Muscle 8:768–777. https://doi.org/10.1002/jcsm.12209

    Article  PubMed  PubMed Central  Google Scholar 

  114. MacIntosh CG, Andrews JM, Jones KL et al (1999) Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation appetite and pyloric motility. Am J Clin Nutr 69:999–1006. https://doi.org/10.1093/ajcn/69.5.999

    CAS  Article  PubMed  Google Scholar 

  115. MacIntosh CG, Morley JE, Wishart J et al (2001) Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging. J Clin Endocrinol Metab 86:5830–5837. https://doi.org/10.1210/jcem.86.12.8107

    CAS  Article  PubMed  Google Scholar 

  116. Mahmassani ZS, Reidy PT, McKenzie AI et al (2019) Age-dependent skeletal muscle transcriptome response to bed rest-induced atrophy. J Appl Physiol 126:894–902

    CAS  Article  Google Scholar 

  117. McClure R, Villani A (2017) Mediterranean diet attenuates risk of frailty and sarcopenia: new insights and future directions. JCSM Clin Reports 2:1–17. https://doi.org/10.17987/jcsm-cr.v2i2.45

    Article  Google Scholar 

  118. McCullough MJ, Peplinski NG, Kinnell KR, Spitsbergen JM (2011) Glial cell line-derived neurotrophic factor (GDNF) protein content in rat skeletal muscle is altered by increased physical activity in vivo and in vitro. Neuroscience 174:234–244. https://doi.org/10.1016/j.neuroscience.2010.11.016

    CAS  Article  PubMed  Google Scholar 

  119. McKay BR, Ogborn DI, Bellamy LM et al (2012) Myostatin is associated with age-related human muscle stem cell dysfunction. FASEB J 26:2509–2521. https://doi.org/10.1096/fj.11-198663

    CAS  Article  PubMed  Google Scholar 

  120. Ming Y, Bergman E, Edström E, Ulfhake B (1999) Evidence for increased GDNF signaling in aged sensory and motor neurons. Neuroreport 10:1529–1535. https://doi.org/10.1097/00001756-199905140-00025

    CAS  Article  PubMed  Google Scholar 

  121. Miyazaki S, Iino N, Koda R et al (2020) Brain-derived neurotrophic factor is associated with sarcopenia and frailty in Japanese hemodialysis patients. Geriatr Gerontol Int. https://doi.org/10.1111/ggi.14089

    Article  PubMed  Google Scholar 

  122. Moore DR, Churchward-Venne TA, Witard O et al (2015) Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. Journals Gerontol - Ser A Biol Sci Med Sci 70:57–62. https://doi.org/10.1093/gerona/glu103

    CAS  Article  Google Scholar 

  123. Moreira-Pais A, Ferreira R, da Costa RG (2018) Platinum-induced muscle wasting in cancer chemotherapy: mechanisms and potential targets for therapeutic intervention. Life Sci 208:1–9. https://doi.org/10.1016/j.lfs.2018.07.010

    CAS  Article  PubMed  Google Scholar 

  124. Morissette MR, Stricker JC, Rosenberg MA et al (2009) Effects of myostatin deletion in aging mice. Aging Cell 8:573–583. https://doi.org/10.1111/j.1474-9726.2009.00508.x

    CAS  Article  PubMed  Google Scholar 

  125. Morley JE (2008) Sarcopenia: diagnosis and treatment. J Nutr Heal Aging 12:452–456. https://doi.org/10.1007/BF02982705

    CAS  Article  Google Scholar 

  126. Mosole S, Carraro U, Kern H et al (2014) Long-term high-level exercise promotes muscle reinnervation with age. J Neuropathol Exp Neurol 73:284–294. https://doi.org/10.1097/NEN.0000000000000032

    CAS  Article  PubMed  Google Scholar 

  127. Muñoz-Cánoves P, Scheele C, Pedersen BK, Serrano AL (2013) Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword ? FEBS J 280:4131–4148. https://doi.org/10.1111/febs.12338

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  128. Murphy KT, Koopman R, Naim T et al (2010) Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function. FASEB J 24:4433–4442. https://doi.org/10.1096/fj.10-159608

    CAS  Article  PubMed  Google Scholar 

  129. O’Connor KG, Tobin JD, Harman SM et al (1998) Serum levels of insulin-like growth factor-I are related to age and not to body composition in healthy women and men. J Gerontol - Ser A Biol Sci Med Sci 53:M176–M182. https://doi.org/10.1093/gerona/53A.3.m176

    Article  Google Scholar 

  130. Oeckinghaus A, Ghosh S (2009) The NF-κB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 1:a000034. https://doi.org/10.1101/cshperspect.a000034

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  131. Olsen M, Krog L, Edvardsen K et al (1993) Intact transmembrane isoforms of the neural cell adhesion molecule are released from the plasma membrane. Biochem J 295:833–840. https://doi.org/10.1042/bj2950833

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  132. Op den Kamp CM, Langen RC, Snepvangers FJ et al (2013) Nuclear transcription factor κB activation and protein turnover adaptations in skeletal muscle of patients with progressive stages of lung cancer cachexia. Am J Clin Nutr 98:738–748. https://doi.org/10.3945/ajcn.113.058388

    CAS  Article  PubMed  Google Scholar 

  133. Ozawa T (2010) Modulation of ryanodine receptor Ca2 + channels (Review). Mol Med Rep 3:199–204. https://doi.org/10.3892/mmr_00000240

    CAS  Article  PubMed  Google Scholar 

  134. Park B, You S, Cho WCS et al (2019) A systematic review of herbal medicines for the treatment of cancer cachexia in animal models. J Zhejiang Univ Sci B 20:9–22. https://doi.org/10.1631/jzus.B1800171

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  135. Penna F, Busquets S, Pin F et al (2011) Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise. J Cachexia Sarcopenia Muscle 2:95–104. https://doi.org/10.1007/s13539-011-0028-4

    Article  PubMed  PubMed Central  Google Scholar 

  136. Peterson SJ, Mozer M (2017) Differentiating sarcopenia and cachexia among patients with cancer. Nutr Clin Pract 32:30–39. https://doi.org/10.1177/0884533616680354

    Article  PubMed  Google Scholar 

  137. Piasecki M, Ireland A, Piasecki J et al (2018) Failure to expand the motor unit size to compensate for declining motor unit numbers distinguishes sarcopenic from non-sarcopenic older men. J Physiol 596:1627–1637. https://doi.org/10.1113/JP275520

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  138. Ratkevicius A, Joyson A, Selmer I et al (2011) Serum concentrations of myostatin and myostatin-interacting proteins do not differ between young and sarcopenic elderly men. J Gerontol - Ser A 66A:620–626. https://doi.org/10.1093/gerona/glr025

    CAS  Article  Google Scholar 

  139. Rivas DA, Morris EP, Haran PH et al (2012) Increased ceramide content and NFκB signaling may contribute to the attenuation of anabolic signaling after resistance exercise in aged males. J Appl Physiol 113:1727–1736. https://doi.org/10.1152/japplphysiol.00412.2012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  140. Roberts BM, Frye GS, Ahn B et al (2013) Cancer cachexia decreases specific force and accelerates fatigue in limb muscle. Biochem Biophys Res Commun 435:488–492. https://doi.org/10.1016/j.bbrc.2013.05.018

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  141. Roberts BM, Lavin KM, Many GM et al (2018) Human neuromuscular aging: sex differences revealed at the myocellular level. Exp Gerontol 106:116–124. https://doi.org/10.1016/j.exger.2018.02.023

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  142. Robinson SM, Reginster JY, Rizzoli R et al (2018) Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr 37:1121–1132. https://doi.org/10.1016/j.clnu.2017.08.016

    CAS  Article  PubMed  Google Scholar 

  143. Rolland Y, Onder G, Morley JE et al (2011) Current and future pharmacologic treatment of sarcopenia. Clin Geriatr Med 27:423–447. https://doi.org/10.1016/j.cger.2011.03.008

    Article  PubMed  Google Scholar 

  144. Rondanelli M, Miccono A, Peroni G et al (2016) A systematic review on the effects of botanicals on skeletal muscle health in order to prevent sarcopenia. Evidence-based Complement Altern Med 2016:5970367. https://doi.org/10.1155/2016/5970367

    CAS  Article  Google Scholar 

  145. Rooks D, Roubenoff R (2019) Development of pharmacotherapies for the treatment of sarcopenia. J Frailty Aging 8:120–130. https://doi.org/10.14283/jfa.2019.11

    CAS  Article  PubMed  Google Scholar 

  146. Rowan SL, Rygiel K, Purves-Smith FM et al (2012) Denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle. PLoS One 7:e29082. https://doi.org/10.1371/journal.pone.0029082

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  147. Rudolf R, Khan MM, Labeit S, Deschenes MR (2014) Degeneration of neuromuscular junction in age and dystrophy. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2014.00099

    Article  PubMed  PubMed Central  Google Scholar 

  148. Russ DW, Grandy JS, Toma K, Ward CW (2011) Ageing, but not yet senescent, rats exhibit reduced muscle quality and sarcoplasmic reticulum function. Acta Physiol 201:391–403. https://doi.org/10.1111/j.1748-1716.2010.02191.x

    CAS  Article  Google Scholar 

  149. Santilli V, Bernetti A, Mangone M, Paoloni M (2014) Clinical definition of sarcopenia. Clin Cases Miner Bone Metab 11:177–180

    PubMed  PubMed Central  Google Scholar 

  150. Schaap LA, Pluijm SMF, Deeg DJH et al (2009) Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol - Ser A Biol Sci Med Sci 64A:1183–1189. https://doi.org/10.1093/gerona/glp097

    CAS  Article  Google Scholar 

  151. Schmidt SF, Rohm M, Herzig S, Berriel Diaz M (2018) Cancer cachexia: more than skeletal muscle wasting. Trends in Cancer 4:849–860. https://doi.org/10.1016/j.trecan.2018.10.001

    CAS  Article  PubMed  Google Scholar 

  152. Sebastián D, Sorianello E, Segalés J et al (2016) Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J 35:1677–1693. https://doi.org/10.15252/embj.201593084

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  153. Secher T (2010) Soluble NCAM. In: Berezin V (ed) Structure and function of the neural cell adhesion molecule NCAM. Springer, Verlag-New York, pp 227–242

    Chapter  Google Scholar 

  154. Serra-Prat M, Papiol M, Monteis R et al (2015) Relationship between plasma ghrelin levels and sarcopenia in elderly subjects: a cross-sectional study. J Nutr Heal Aging 19:669–672. https://doi.org/10.1007/s12603-015-0550-8

    CAS  Article  Google Scholar 

  155. Smiechowska J, Utech A, Taffet G et al (2010) Adipokines in patients with cancer anorexia and cachexia. J Investig Med 58:554–559. https://doi.org/10.2310/JIM.0b013e3181cf91ca

    CAS  Article  PubMed  Google Scholar 

  156. Smith GI, Julliand S, Reeds DN et al (2015) Fish oil-derived n-3 PUFA therapy increases muscle mass and function in healthy older adults. Am J Clin Nutr 102:115–122. https://doi.org/10.3945/ajcn.114.105833

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  157. Snijders T, Nederveen JP, McKay BR et al (2015) Satellite cells in human skeletal muscle plasticity. Front Physiol 6:283. https://doi.org/10.3389/fphys.2015.00283

    Article  PubMed  PubMed Central  Google Scholar 

  158. St-Jean-Pelletier F, Pion CH, Leduc-Gaudet JP et al (2017) The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men. J Cachexia Sarcopenia Muscle 8:213–228. https://doi.org/10.1002/jcsm.12139

    Article  PubMed  Google Scholar 

  159. Stevens L, Firinga C, Gohlsch B et al (2000) Effects of unweighting and clenbuterol on myosin light and heavy chains in fast and slow muscles of rat. Am J Physiol - Cell Physiol 279:C1558–C1563. https://doi.org/10.1152/ajpcell.2000.279.5.c1558

    CAS  Article  PubMed  Google Scholar 

  160. Storer TW, Basaria S, Traustadottir T et al (2017) Effects of testosterone supplementation for 3-years on muscle performance and physical function in older men. J Clin Endocrinol Metab 102:583–593. https://doi.org/10.1210/jc.2016-2771

    Article  PubMed  Google Scholar 

  161. Taetzsch T, Tenga MJ, Valdez G (2017) Muscle fibers secrete FGFBP1 to slow degeneration of neuromuscular synapses during aging and progression of ALS. J Neurosci 37:70–82. https://doi.org/10.1523/JNEUROSCI.2992-16.2016

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  162. Talmadge RJ (2000) Myosin heavy chain isoform expression following reduced neuromuscular activity: potential regulatory mechanisms. Muscle Nerve 23:661–679

    CAS  Article  Google Scholar 

  163. Tanaka M, Sugimoto K, Fujimoto T et al (2019) Preventive effects of low-intensity exercise on cancer cachexia–induced muscle atrophy. FASEB J 33:7852–7862. https://doi.org/10.1096/fj.201802430R

    CAS  Article  PubMed  Google Scholar 

  164. Taskin S, Stumpf VI, Bachmann J et al (2014) Motor protein function in skeletal abdominal muscle of cachectic cancer patients. J Cell Mol Med 18:69–79. https://doi.org/10.1111/jcmm.12165

    CAS  Article  PubMed  Google Scholar 

  165. Tomlinson BE, Irving D (1977) The numbers of limb motor neurons in the human lumbosacral cord throughout life. J Neurol Sci 34:213–219

    CAS  Article  Google Scholar 

  166. Townsend JR, Hoffman JR, Fragala MS et al (2016) A microbiopsy method for immunohistological and morphological analysis: a pilot study. Med Sci Sports Exerc 48:331–335. https://doi.org/10.1249/MSS.0000000000000772

    CAS  Article  PubMed  Google Scholar 

  167. Troiano AR, Schulzer M, De La Fuente-Fernandez R et al (2010) Dopamine transporter PET in normal aging: dopamine transporter decline and its possible role in preservation of motor function. Synapse 64:146–151. https://doi.org/10.1002/syn.20708

    CAS  Article  PubMed  Google Scholar 

  168. Tsay H-J, Schmidt J (1989) Skeletal muscle denervation activates acetylcholine receptor genes. J Cell Biol 108:1523–1526. https://doi.org/10.1083/jcb.108.4.1523

    CAS  Article  PubMed  Google Scholar 

  169. Uchitomi R, Hatazawa Y, Senoo N et al (2019) Metabolomic analysis of skeletal muscle in aged mice. Sci Rep 9:10425. https://doi.org/10.1038/s41598-019-46929-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  170. Valdez G, Tapia JC, Kang H et al (2010) Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise. Proc Natl Acad Sci U S A 107:14863–14868. https://doi.org/10.1073/pnas.1002220107

    Article  PubMed  PubMed Central  Google Scholar 

  171. Veyrat-Durebex C, Quirion R, Ferland G et al (2013) Aging and long-term caloric restriction regulate neuropeptide Y receptor subtype densities in the rat brain. Neuropeptides 47:163–169. https://doi.org/10.1016/j.npep.2013.01.001

    CAS  Article  PubMed  Google Scholar 

  172. Visser M, Pahor M, Taaffe DR et al (2002) Relationship of interleukin-6 and tumor necrosis factor-α with muscle mass and muscle strength in elderly men and women: the health ABC study. J Gerontol - Ser A Biol Sci Med Sci 57A:M326–M332. https://doi.org/10.1093/gerona/57.5.m326

    CAS  Article  Google Scholar 

  173. Wåhlin-Larsson B, Carnac G, Kadi F (2014) The influence of systemic inflammation on skeletal muscle in physically active elderly women. Age (Omaha) 36:9718. https://doi.org/10.1007/s11357-014-9718-0

    CAS  Article  Google Scholar 

  174. Wåhlin-Larsson B, Wilkinson DJ, Strandberg E et al (2017) Mechanistic links underlying the impact of c-reactive protein on muscle mass in elderly. Cell Physiol Biochem 44:267–278. https://doi.org/10.1159/000484679

    Article  PubMed  Google Scholar 

  175. Weryńska B, Kosacka M, Gołecki M, Jankowska R (2009) Leptin serum levels in cachectic and non-cachectic lung cancer patients. Adv Respir Med 77:500–506

    Google Scholar 

  176. Wesley Peixoto da Fonseca G, Farkas J, Dora E et al (2020) Cancer cachexia and related metabolic dysfunction. Int J Mol Sci 21:2321. https://doi.org/10.3390/ijms21072321

    CAS  Article  Google Scholar 

  177. Westbury LD, Fuggle NR, Syddall HE et al (2018) Relationships between markers of inflammation and muscle mass, strength and function: findings from the Hertfordshire Cohort Study. Calcif Tissue Int 102:287–295. https://doi.org/10.1007/s00223-017-0354-4

    CAS  Article  PubMed  Google Scholar 

  178. Wham CA, Bowden JA (2011) Eating for health: perspectives of older men who live alone. Nutr Diet 68:221–226. https://doi.org/10.1111/j.1747-0080.2011.01535.x

    Article  Google Scholar 

  179. White JP, Baynes JW, Welle SL et al (2011) The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc Min/+ mouse. PLoS One 6:e24650. https://doi.org/10.1371/journal.pone.0024650

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  180. Wilkinson DJ, Piasecki M, Atherton PJ (2018) The age-related loss of skeletal muscle mass and function: measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans. Ageing Res Rev 47:123–132. https://doi.org/10.1016/j.arr.2018.07.005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  181. Winter A, MacAdams J, Chevalier S (2012) Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia. Clin Nutr 31:765–773. https://doi.org/10.1016/j.clnu.2012.05.003

    CAS  Article  PubMed  Google Scholar 

  182. Wu J, Huang C, Xiao H et al (2013) Weight loss and resting energy expenditure in male patients with newly diagnosed esophageal cancer. Nutrition 29:1310–1314. https://doi.org/10.1016/j.nut.2013.04.010

    Article  PubMed  Google Scholar 

  183. Wyczalkowska-Tomasik A, Czarkowska-Paczek B, Zielenkiewicz M, Paczek L (2016) Inflammatory markers change with age, but do not fall beyond reported normal ranges. Arch Immunol Ther Exp (Warsz) 64:249–254. https://doi.org/10.1007/s00005-015-0357-7

    CAS  Article  Google Scholar 

  184. Xia Z, Cholewa J, Zhao Y et al (2017) Targeting inflammation and downstream protein metabolism in sarcopenia: a brief up-dated description of concurrent exercise and leucine-based multimodal intervention. Front Physiol 8:434. https://doi.org/10.3389/fphys.2017.00434

    Article  PubMed  PubMed Central  Google Scholar 

  185. Yarasheski KE, Bhasin S, Sinha-Hikim I et al (2002) Serum myostatin-immunoreactive protein is increased in 60–92 year old women and men with muscle wasting. J Nutr Heal Aging 6:343–348

    CAS  Google Scholar 

  186. Yazar T, Olgun Yazar H (2019) Prevalance of sarcopenia according to decade. Clin Nutr ESPEN 29:137–141. https://doi.org/10.1016/j.clnesp.2018.11.005

    Article  PubMed  Google Scholar 

  187. Zhao K, Shen C, Li L et al (2018) Sarcoglycan alpha mitigates neuromuscular junction decline in aged mice by stabilizing LRP4. J Neurosci 38:8860–8873. https://doi.org/10.1523/JNEUROSCI.0860-18.2018

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by CIAFEL (UIDB/00617/2020), LAQV (UIDB/50006/2020) and CITAB (UIDB/04033/2020) research units and by A.M.P.’s fellowship (SFRH/BD/144396/2019) through national founds by the Portuguese Foundation for Science and Technology (FCT) and co-financed by the European Regional Development Fund (FEDER), within the PT2020 Partnership Agreement.

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Moreira-Pais, A., Ferreira, R., Oliveira, P.A. et al. Sarcopenia versus cancer cachexia: the muscle wasting continuum in healthy and diseased aging. Biogerontology 22, 459–477 (2021). https://doi.org/10.1007/s10522-021-09932-z

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Keywords

  • Aging
  • Circulating players
  • Disuse
  • Inflammation
  • Neuromuscular
  • Nutrition