{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:06:05Z","timestamp":1790431565383,"version":"4.1.0"},"reference-count":150,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K00414X\/1"],"award-info":[{"award-number":["MR\/K00414X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["19891"],"award-info":[{"award-number":["19891"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy, and insulin resistance with age and disease in humans, little is known about the mechanisms responsible for these negative traits. With the complexities surrounding these unknowns and the lack of progress to date in development of effective interventions, there is a need for alternative approaches. Metabolomics is the study of the full array of metabolites within cells or tissues, which collectively constitute the metabolome. As metabolomics allows for the assessment of the cellular metabolic state in response to physiological stimuli, any chronic change in the metabolome is likely to reflect adaptation in the physiological phenotype of an organism. This, therefore, provides a holistic and unbiased approach that could be applied to potentially uncover important novel facets in the pathophysiology of muscle decline in ageing and disease, as well as identifying prognostic markers of those at risk of decline. This review will aim to highlight the current knowledge and potential impact of metabolomics in the study of muscle mass loss and deconditioning in humans and will highlight key areas for future research.<\/jats:p>","DOI":"10.3390\/ijms222413575","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4007-9361","authenticated-orcid":false,"given":"Isabelle","family":"Alldritt","sequence":"first","affiliation":[{"name":"MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"School of Medicine, Royal Derby Hospital Centre, University of Nottingham, Derby DE22 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4403-0490","authenticated-orcid":false,"given":"Paul L.","family":"Greenhaff","sequence":"additional","affiliation":[{"name":"MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"School of Life Sciences, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"School of Medicine, Royal Derby Hospital Centre, University of Nottingham, Derby DE22 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/ajcn\/84.3.475","article-title":"The underappreciated role of muscle in health and disease","volume":"84","author":"Wolfe","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.clnu.2014.03.007","article-title":"Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: From sarcopenic obesity to cachexia","volume":"33","author":"Biolo","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_3","first-page":"183","article-title":"Skeletal Muscle: A Brief Review of Structure and Function","volume":"45","author":"Frontera","year":"2015","journal-title":"Behav. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.jamda.2016.04.019","article-title":"Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease","volume":"17","author":"Campos","year":"2016","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1136\/pgmj.2004.020891","article-title":"Cachexia in malaria and heart failure: Therapeutic considerations in clinical practice","volume":"80","author":"Onwuamaegbu","year":"2004","journal-title":"Postgrad. Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s13539-011-0019-5","article-title":"Wasting in chronic kidney disease","volume":"2","author":"Mak","year":"2011","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6948","DOI":"10.1158\/0008-5472.CAN-11-1095","article-title":"Metabolic Signatures Imaged in Cancer-Induced Cachexia","volume":"71","author":"Penet","year":"2011","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1006\/bbrc.2001.4497","article-title":"The transcription factors NF-\u03baB and AP-1 are differentially regulated in skeletal muscle during sepsis","volume":"281","author":"Penner","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","first-page":"2042018819888824","article-title":"Reduced physical activity in young and older adults: Metabolic and musculoskeletal implications","volume":"10","author":"Pickles","year":"2019","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/cphy.c110025","article-title":"Lack of Exercise Is a Major Cause of Chronic Diseases","volume":"2","author":"Booth","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/978-3-319-57379-3_19","article-title":"Sarcopenia and Its Impact on Quality of Life","volume":"Volume 987","author":"Vlamos","year":"2017","journal-title":"GeNeDis 2016: Advances in Experimental Medicine and Biology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110801","DOI":"10.1016\/j.exger.2019.110801","article-title":"Prevalence of sarcopenia as a comorbid disease: A systematic review and meta-analysis","volume":"131","author":"Pacifico","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, L., Nelson, D.R., Zhao, Y., Cui, Z., and Johnston, J.A. (2013). Relationship between muscle mass and muscle strength, and the impact of comorbidities: A population-based, Cross-sectional study of older adults in the United States. BMC Geriatr., 13.","DOI":"10.1186\/1471-2318-13-74"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6561","DOI":"10.1158\/1078-0432.CCR-07-0116","article-title":"Human Cancer Biology Defining Cancer Cachexia in Head and Neck Squamous Cell Carcinoma","volume":"13","author":"Richey","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1152\/japplphysiol.00452.2009","article-title":"Alterations of protein turnover underlying disuse atrophy in human skeletal muscle","volume":"107","author":"Phillips","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E594","DOI":"10.1152\/ajpendo.00257.2016","article-title":"Control of skeletal muscle atrophy in response to disuse: Clinical\/preclinical contentions and fallacies of evidence","volume":"311","author":"Atherton","year":"2016","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3389\/fphys.2016.00361","article-title":"Human skeletal muscle disuse atrophy: Effects on muscle protein synthesis, breakdown, and insulin resistance-A qualitative review","volume":"7","author":"Rudrappa","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jamda.2011.01.003","article-title":"Sarcopenia: An Undiagnosed Condition in Older Adults. Current Consensus Definition: Prevalence, Etiology, and Consequences. International Working Group on Sarcopenia","volume":"12","author":"Fielding","year":"2011","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.clnu.2008.06.013","article-title":"Cachexia: A new definition","volume":"27","author":"Evans","year":"2008","journal-title":"Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jamda.2011.04.014","article-title":"Sarcopenia With Limited Mobility: An International Consensus","volume":"12","author":"Morley","year":"2011","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jamda.2013.11.025","article-title":"Sarcopenia in Asia: Consensus report of the Asian working group for sarcopenia","volume":"15","author":"Chen","year":"2014","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s11357-012-9384-z","article-title":"Defining sarcopenia: The impact of different diagnostic criteria on the prevalence of sarcopenia in a large middle aged cohort","volume":"35","author":"Bijlsma","year":"2013","journal-title":"Age"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104125","DOI":"10.1016\/j.archger.2020.104125","article-title":"Impact of using the updated EWGSOP2 definition in diagnosing sarcopenia: A clinical perspective","volume":"90","author":"Alcazar","year":"2020","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e000097","DOI":"10.1136\/bmjgast-2016-000097","article-title":"Cachexia in cancer: What is in the definition?","volume":"3","author":"Vanhoutte","year":"2016","journal-title":"BMJ Open Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1080\/01635581.2018.1504092","article-title":"Cancer Cachexia: Identification by Clinical Assessment versus International Consensus Criteria in Patients with Metastatic Colorectal Cancer","volume":"70","author":"Verheul","year":"2018","journal-title":"Nutr. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1023\/A:1020151401826","article-title":"Age-related changes in type 1 and type 2 cytokine production in humans","volume":"3","author":"Gardner","year":"2002","journal-title":"Biogerontology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1093\/gerona\/glq056","article-title":"Inflammatory Markers and Physical Performance Among Nonagenarians","volume":"65","author":"Tiainen","year":"2010","journal-title":"J. Gerontol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.clnu.2011.07.010","article-title":"Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia?","volume":"31","author":"Watt","year":"2012","journal-title":"Clin. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.archger.2014.08.004","article-title":"Inflammatory mediators, muscle and functional performance of community-dwelling elderly women","volume":"59","author":"Felicio","year":"2014","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/s00223-014-9894-z","article-title":"Lean Mass, Muscle Strength and Gene Expression in Community Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study ( HSS )","volume":"95","author":"Patel","year":"2014","journal-title":"Calcif. Tissue Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.maturitas.2016.11.006","article-title":"Inflammation and sarcopenia: A systematic review and meta-analysis","volume":"96","author":"Bano","year":"2017","journal-title":"Maturitas"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00467-017-3684-6","article-title":"Muscle wasting in chronic kidney disease","volume":"33","author":"Oliveira","year":"2018","journal-title":"Pediatr. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12986-019-0409-9","article-title":"Plasma concentration of interleukin-6 was upregulated in cancer cachexia patients and was positively correlated with plasma free fatty acid in female patients","volume":"16","author":"Han","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.pan.2018.11.002","article-title":"Pancreatology Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer","volume":"19","author":"Ramsey","year":"2019","journal-title":"Pancreatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s10522-018-9775-3","article-title":"Age-related changes in skeletal muscle: Changes to life-style as a therapy","volume":"19","author":"McCormick","year":"2018","journal-title":"Biogerontology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1177\/1758834017698643","article-title":"Cancer-induced muscle wasting: Latest findings in prevention and treatment","volume":"9","author":"Aversa","year":"2017","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nbt.3557","article-title":"No longer going to waste","volume":"34","author":"Garber","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1017\/S0954422413000115","article-title":"Nutritional strategies to counteract muscle atrophy caused by disuse and to improve recovery","volume":"26","author":"Magne","year":"2013","journal-title":"Nutr. Res. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13059-017-1215-1","article-title":"Multi-omics approaches to disease","volume":"18","author":"Hasin","year":"2017","journal-title":"Genome Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s10038-020-0763-5","article-title":"Interpretation of omics data analyses","volume":"66","author":"Yamada","year":"2021","journal-title":"J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/bies.10385","article-title":"Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era","volume":"26","author":"Kell","year":"2004","journal-title":"BioEssays"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1576\/toag.13.3.189.27672","article-title":"\u2018Omic\u2019 technologies: Genomics, transcriptomics, proteomics and metabolomics","volume":"13","author":"Horgan","year":"2011","journal-title":"Obstet. Gynaecol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10999","DOI":"10.1038\/s41598-020-67929-z","article-title":"Circulating proteomic signature for detection of biomarkers in bladder cancer patients","volume":"10","author":"Nedjadi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Amon, L.M., Law, W., Fitzgibbon, M.P., Gross, J.A., O\u2019Briant, K., Peterson, A., Drescher, C., Martin, D.B., and McIntosh, M. (2010). Integrative Proteomic Analysis of Serum and Peritoneal Fluids Helps Identify Proteins that Are Up-Regulated in Serum of Women with Ovarian Cancer. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011137"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.jprot.2010.03.005","article-title":"On the identification of biomarkers for non-small cell lung cancer in serum and pleural effusion","volume":"73","year":"2010","journal-title":"J. Proteom."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1016\/j.jmb.2017.06.019","article-title":"Transcriptional Signatures of Aging","volume":"429","author":"Stegeman","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sood, S., Gallagher, I.J., Lunnon, K., Rullman, E., Keohane, A., Crossland, H., Phillips, B.E., Cederholm, T., Jensen, T., and van Loon, L.J.C. (2015). A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status. Genome Biol., 16.","DOI":"10.1186\/s13059-015-0750-x"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12970","DOI":"10.1111\/acel.12970","article-title":"Longevity-related molecular pathways are subject to midlife \u201cswitch\u201d in humans","volume":"18","author":"Timmons","year":"2019","journal-title":"Aging Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0167-7799(98)01214-1","article-title":"Systematic functional analysis of the yeast genome","volume":"16","author":"Oliver","year":"1998","journal-title":"Trends Biotechnol."},{"key":"ref_53","unstructured":"Brown, S.D., Tauler, R., and Walczak, B. (2009). 4.08\u2014Analysis of Megavariate Data in Functional Genomics. Comprehensive Chemometrics, Elsevier."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1023\/A:1013713905833","article-title":"Metabolomics\u2014The link between genotypes and phenotypes","volume":"48","author":"Fiehn","year":"2002","journal-title":"Plant Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jpba.2014.12.017","article-title":"Metabolomics for laboratory diagnostics","volume":"113","author":"Bujak","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1007\/s13361-016-1469-y","article-title":"Untargeted Metabolomics Strategies\u2014Challenges and Emerging Directions","volume":"27","author":"Codreanu","year":"2016","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tolstikov, V., James Moser, A., Sarangarajan, R., Narain, N.R., and Kiebish, M.A. (2020). Current status of metabolomic biomarker discovery: Impact of study design and demographic characteristics. Metabolites, 10.","DOI":"10.3390\/metabo10060224"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1002\/mds.27132","article-title":"Distinct Metabolomic Signature in Cerebrospinal Fluid in Early Parkinson\u2019s Disease","volume":"32","author":"Trezzi","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nm.3466","article-title":"Plasma phospholipids identify antecedent memory impairment in older adults","volume":"20","author":"Mapstone","year":"2014","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1136\/jnnp-2020-323611","article-title":"Untargeted metabolomics yields insight into ALS disease mechanisms","volume":"91","author":"Goutman","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.3748\/wjg.v23.i15.2771","article-title":"Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease","volume":"23","author":"Dong","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Roberts, L.D., Souza, A.L., Gerszten, R.E., and Clish, C.B. (2012). Targeted metabolomics. Curr. Protoc. Mol. Biol., 30.2.1\u201330.2.24.","DOI":"10.1002\/0471142727.mb3002s98"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1126\/scitranslmed.3001006","article-title":"Metabolic Signatures of Exercise in Human Plasma","volume":"2","author":"Lewis","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1002\/jcp.24002","article-title":"Challenges and opportunities of metabolomics","volume":"227","author":"Johnson","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/gerona\/glt152","article-title":"Branched Chain Amino Acids Are Associated With Muscle Mass in Functionally Limited Older Adults","volume":"69","author":"Lustgarten","year":"2014","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ejhg.2015.85","article-title":"Genomics and metabolomics of muscular mass in a community-based sample of UK females","volume":"24","author":"Korostishevsky","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1093\/gerona\/glw046","article-title":"Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging","volume":"71","author":"Moaddel","year":"2016","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12603-018-1108-3","article-title":"Low Levels of Branched Chain Amino Acids, Eicosapentaenoic Acid and Micronutrients are Associated with Low Muscle Mass, Strength and Function in Community-Dwelling Older Adults","volume":"23","author":"Luiking","year":"2019","journal-title":"J. Nutr. Health Aging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s12603-018-1014-8","article-title":"Plasma Amino Acid Concentrations Are Associated with Muscle Function in Older Japanese Women","volume":"22","author":"Yamada","year":"2018","journal-title":"J. Nutr. Health Aging"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Toyoshima, K., Nakamura, M., Adachi, Y., Imaizumi, A., Hakamada, T., Abe, Y., Kaneko, E., Takahashi, S., and Shimokado, K. (2017). Increased plasma proline concentrations are associated with sarcopenia in the elderly. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185206"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.18632\/aging.101574","article-title":"A joint analysis of metabolomic profiles associated with muscle mass and strength in Caucasian women","volume":"10","author":"Zhao","year":"2018","journal-title":"Aging"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Calvani, R., Picca, A., Marini, F., Biancolillo, A., Gervasoni, J., Persichilli, S., Primiano, A., Bossola, M., Urbani, A., and Landi, F. (2018). A Distinct Pattern of Circulating Amino Acids Characterizes Older Persons with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study. Nutrients, 10.","DOI":"10.20944\/preprints201809.0224.v1"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ijge.2018.03.003","article-title":"Plasma Amino Acid Profile in Severely Frail Elderly Patients in Japan","volume":"12","author":"Adachi","year":"2018","journal-title":"Int. J. Gerontol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/jcsm.12270","article-title":"Multiplatform plasma fingerprinting in cancer cachexia: A pilot observational and translational study","volume":"9","author":"Cala","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ose, J., Gigic, B., Lin, T., Liesenfeld, D.B., B\u00f6hm, J., Nattenm\u00fcller, J., Scherer, D., Zielske, L., Schrotz-King, P., and Habermann, N. (2019). Multiplatform urinary metabolomics profiling to discriminate cachectic from non-cachectic colorectal cancer patients: Pilot results from the colocare study. Metabolites, 9.","DOI":"10.3390\/metabo9090178"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/jcsm.12246","article-title":"Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia","volume":"9","author":"Yang","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1093\/ije\/dyw033","article-title":"Objectively measured physical activity and plasma metabolomics in the Shanghai Physical Activity Study","volume":"45","author":"Xiao","year":"2016","journal-title":"Int. J. Epidemiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Fukai, K., Harada, S., Iida, M., Kurihara, A., Takeuchi, A., Kuwabara, K., Sugiyama, D., Okamura, T., Akiyama, M., and Nishiwaki, Y. (2016). Metabolic Profiling of Total Physical Activity and Sedentary Behavior in Community-Dwelling Men. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164877"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Saoi, M., Li, A., McGlory, C., Stokes, T., Von Allmen, M.T., Phillips, S.M., and Britz-McKibbin, P. (2019). Metabolic Perturbations from Step Reduction in Older Persons at Risk for Sarcopenia: Plasma Biomarkers of Abrupt Changes in Physical Activity. Metabolites, 9.","DOI":"10.3390\/metabo9070134"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1039\/c2mb25194a","article-title":"Targeted metabolomics identifies perturbations in amino acid metabolism that sub-classify patients with COPD","volume":"8","author":"Ubhi","year":"2012","journal-title":"Mol. Biosyst."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/MCC.0000000000000488","article-title":"Defining anabolic resistance: Implications for delivery of clinical care nutrition","volume":"24","author":"Morton","year":"2018","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1096\/fj.04-2640fje","article-title":"Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle","volume":"19","author":"Cuthbertson","year":"2005","journal-title":"FASEB J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1113\/jphysiol.2008.164483","article-title":"Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men","volume":"587","author":"Kumar","year":"2009","journal-title":"J. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/gerona\/glu103","article-title":"Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men","volume":"70","author":"Moore","year":"2015","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e12433","DOI":"10.14814\/phy2.12433","article-title":"Internal comparison between deuterium oxide (D2O) and L-[ring-13C6] phenylalanine for acute measurement of muscle protein synthesis in humans","volume":"3","author":"Wilkinson","year":"2015","journal-title":"Physiol. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.arr.2018.07.005","article-title":"The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans","volume":"47","author":"Wilkinson","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/jcsm.12029","article-title":"Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients","volume":"6","author":"Moses","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.3945\/ajcn.112.045708","article-title":"Effect of tumor burden and subsequent surgical resection on skeletal muscle mass and protein turnover in colorectal cancer patients","volume":"96","author":"Williams","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"E137","DOI":"10.1152\/ajpendo.00227.2015","article-title":"Short-term muscle disuse lowers myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion","volume":"310","author":"Wall","year":"2016","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1210\/jc.2013-1502","article-title":"Two weeks of reduced activity decreases leg lean mass and induces \u201canabolic resistance\u201d of myofibrillar protein synthesis in healthy elderly","volume":"98","author":"Breen","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1113\/jphysiol.2011.225003","article-title":"Muscle protein synthesis in response to nutrition and exercise","volume":"590","author":"Atherton","year":"2012","journal-title":"J. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Jourdan, C., Petersen, A.-K., Gieger, C., Doring, A., Illig, T., Wang-Sattler, R., Meisinger, C., Peters, A., Adamski, J., and Prehn, C. (2012). Body Fat Free Mass Is Associated with the Serum Metabolite Profile in a Population-Based Study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040009"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Yoon, M. (2016). The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism. Nutrients, 8.","DOI":"10.3390\/nu8070405"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.3945\/ajcn.2009.27543","article-title":"Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia","volume":"90","author":"Wilkes","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1016\/j.jchromb.2010.05.031","article-title":"Simultaneous determination of cytosine arabinoside, daunorubicin and etoposide in human plasma","volume":"878","author":"Hansen","year":"2010","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1152\/jappl.1991.70.3.1245","article-title":"Seven days of bed rest decrease insulin action on glucose uptake in leg and whole body","volume":"70","author":"Mikines","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1113\/JP281021","article-title":"Immobilisation induces sizeable and sustained reductions in forearm glucose uptake in just 24 h but does not change lipid uptake in healthy men The Journal of Physiology","volume":"8","author":"Burns","year":"2021","journal-title":"J. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/00075197-200501000-00007","article-title":"Skeletal muscle glutamate metabolism in health and disease: State of the art","volume":"8","author":"Rutten","year":"2005","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"578","DOI":"10.2741\/3707","article-title":"Regulation of protein metabolism by glutamine: Implications for nutrition and health","volume":"16","author":"Xi","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2046-2395-3-9","article-title":"It is not just muscle mass: A review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life","volume":"3","author":"McGregor","year":"2014","journal-title":"Longev. Health"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3","DOI":"10.21037\/apm.2018.12.01","article-title":"Cancer cachexia is defined by an ongoing loss of skeletal muscle mass","volume":"8","author":"Baracos","year":"2019","journal-title":"Ann. Palliat. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jcsm.12259","article-title":"Short-term disuse promotes fatty acid infiltration into skeletal muscle","volume":"9","author":"Pagano","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/gerona\/glp179","article-title":"The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure","volume":"65","author":"Crane","year":"2010","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1152\/jappl.2000.88.2.662","article-title":"Skeletal muscle contractile and noncontractile components in young and older women and men","volume":"88","author":"Ng","year":"2000","journal-title":"J. Appl. Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/02841860802130001","article-title":"Morphology, metabolism, microcirculation, and strength of skeletal muscles in cancer-related cachexia muscles in cancer-related cachexia","volume":"48","author":"Weber","year":"2009","journal-title":"Acta Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s13539-011-0030-x","article-title":"Intramyocellular lipid droplets increase with progression of cachexia in cancer patients","volume":"2","author":"Stephens","year":"2011","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e13135","DOI":"10.1111\/acel.13135","article-title":"Older adults with sarcopenia have distinct skeletal muscle phosphodiester, phosphocreatine, and phospholipid profiles","volume":"19","author":"Hinkley","year":"2020","journal-title":"Aging Cell"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Miller, J., Alsheri, A., Ramage, M.I., Stephens, N.A., Mullen, A.B., Boyd, M., Ross, J.A., Wigmore, S.J., Watson, D.G., and Skipworth, R.J.E. (2019). Plasma Metabolomics Identifies Lipid and Amino Acid Markers of Weight Loss in Patients with Upper Gastrointestinal Cancer. Cancers, 11.","DOI":"10.3390\/cancers11101594"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Law, S.H., Chan, M.L., Marathe, G.K., Parveen, F., Chen, C.H., and Ke, L.Y. (2019). An updated review of lysophosphatidylcholine metabolism in human diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051149"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/01.mco.0000165004.93707.88","article-title":"Systemic inflammation, cachexia and prognosis in patients with cancer","volume":"8","author":"Deans","year":"2005","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"13","DOI":"10.21037\/apm.2018.10.01","article-title":"Lipid metabolism in cancer cachexia","volume":"8","author":"Dalal","year":"2019","journal-title":"Ann. Palliat. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1111\/j.1349-7006.2010.01582.x","article-title":"Role of b 1-adrenoceptor in increased lipolysis in cancer cachexia","volume":"101","author":"Cao","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1158\/0008-5472.CAN-06-4585","article-title":"Mechanism of Increased Lipolysis in Cancer Cachexia","volume":"67","author":"Agustsson","year":"2007","journal-title":"Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.metabol.2009.09.014","article-title":"Twenty-eight-day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides","volume":"59","author":"Cree","year":"2010","journal-title":"Metabolism."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2337\/db08-0263","article-title":"Physical inactivity differentially alters dietary oleate and palmitate trafficking","volume":"58","author":"Bergouignan","year":"2009","journal-title":"Diabetes"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.2337\/db15-1661","article-title":"One week of bed rest leads to substantial muscle atrophy and induces whole-body insulin resistance in the absence of skeletal muscle lipid accumulation","volume":"65","author":"Dirks","year":"2016","journal-title":"Diabetes"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.nut.2009.07.004","article-title":"Body composition changes with aging: The cause or the result of alterations in metabolic rate and macronutrient oxidation?","volume":"26","author":"Gallagher","year":"2010","journal-title":"Nutrition"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s41048-015-0013-0","article-title":"Skeletal intramyocellular lipid metabolism and insulin resistance","volume":"1","author":"Li","year":"2015","journal-title":"Biophys. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s00125-012-2597-y","article-title":"Revisiting the connection between intramyocellular lipids and insulin resistance: A long and winding road","volume":"55","author":"Muoio","year":"2012","journal-title":"Diabetologia"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.bbalip.2017.07.010","article-title":"Intramyocellular lipid droplets and insulin sensitivity, the human perspective","volume":"1862","author":"Gemmink","year":"2017","journal-title":"Biochim. Biophys. Acta-Mol. Cell Biol. Lipids"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1152\/ajpendo.00062.2017","article-title":"Lipid droplet size and location in human skeletal muscle fibers are associated with insulin sensitivity","volume":"313","author":"Nielsen","year":"2017","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.molmet.2018.08.004","article-title":"Distinct lipid droplet characteristics and distribution unmask the apparent contradiction of the athlete\u2019s paradox","volume":"17","author":"Daemen","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1007\/s00125-020-05170-z","article-title":"Exercising your fat (metabolism) into shape: A muscle-centred view","volume":"63","author":"Gemmink","year":"2020","journal-title":"Diabetologia"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1172\/JCI104453","article-title":"Heterogeneity of forearm metabolism with special reference to free fatty acids","volume":"41","author":"Baltzan","year":"1962","journal-title":"J. Clin. Investig."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1172\/JCI103324","article-title":"The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state; measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm","volume":"35","author":"Andres","year":"1956","journal-title":"J. Clin. Investig."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"987","DOI":"10.2337\/db07-1429","article-title":"Mitochondrial Capacity in Skeletal Muscle Is Not Stimulated by Weight Loss Despite Increases in Insulin Action and Decreases in Intramyocellular Lipid Content","volume":"57","author":"Toledo","year":"2008","journal-title":"Diabetes"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"5618","DOI":"10.1073\/pnas.0501559102","article-title":"Decline in skeletal muscle mitochondrial function with aging in humans","volume":"102","author":"Short","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"8548","DOI":"10.1038\/s41598-018-26944-x","article-title":"Mitochondrial function is impaired in the skeletal muscle of pre-frail elderly","volume":"8","author":"Andreux","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/gerona\/gls196","article-title":"Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults","volume":"68","author":"Coen","year":"2013","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1093\/gerona\/glaa001","article-title":"Skeletal Muscle Energetics and Mitochondrial Function Are Impaired Following 10 Days of Bed Rest in Older Adults","volume":"75","author":"Standley","year":"2020","journal-title":"J. Gerontol. Med. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"474","DOI":"10.3389\/fphys.2019.00474","article-title":"Mitochondrial Adaptations in Elderly and Young Men Skeletal Muscle Following 2 Weeks of Bed Rest and Rehabilitation","volume":"10","author":"Buso","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_132","first-page":"15","article-title":"Nuclear magnetic resonance in conjunction with functional genomics suggests mitochondrial dysfunction in a murine model of cancer cachexia","volume":"27","author":"Constantinou","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"de Castro, G.S., Simoes, E., Lima, J.D.C.C., Ortiz-Silva, M., Festuccia, W.T., Tokeshi, F., Alc\u00e2ntara, P.S., Otoch, J.P., Coletti, D., and Seelaender, M. (2019). Human cachexia induces changes in mitochondria, autophagy and apoptosis in the skeletal muscle. Cancers, 11.","DOI":"10.3390\/cancers11091264"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1002\/jcsm.12232","article-title":"Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice","volume":"8","author":"Brown","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/jcsm.12597","article-title":"Metabolic profiling shows pre-existing mitochondrial dysfunction contributes to muscle loss in a model of ICU-acquired weakness","volume":"11","author":"Kemp","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00204-013-1118-1","article-title":"Circulating acylcarnitines as biomarkers of mitochondrial dysfunction after acetaminophen overdose in mice and humans","volume":"88","author":"McGill","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"111405","DOI":"10.1016\/j.mad.2020.111405","article-title":"Novel metabolomics markers are associated with pre-clinical decline in hand grip strength in community-dwelling older adults","volume":"193","author":"Ng","year":"2021","journal-title":"Mech. Ageing Dev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/acs.jproteome.5b00840","article-title":"The Muscle Metabolome Differs between Healthy and Frail Older Adults","volume":"15","author":"Fazelzadeh","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s00216-009-3289-4","article-title":"1H NMR-based metabolomics approach for exploring urinary metabolome modifications after acute and chronic physical exercise","volume":"396","author":"Enea","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"6405","DOI":"10.1021\/pr100684t","article-title":"H NMR-Based Metabonomic Investigation of the Effect of Two Different Exercise Sessions on the Metabolic Fingerprint of Human Urine","volume":"9","author":"Pechlivanis","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1152\/jn.00685.2005","article-title":"Doublet discharges in motoneurons of young and older adults","volume":"95","author":"Christie","year":"2006","journal-title":"J. Neurophysiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.apmr.2008.09.565","article-title":"Age-Associated Changes in Motor Unit Physiology: Observations from the Baltimore Longitudinal Study of Aging","volume":"90","author":"Ling","year":"2009","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1113\/JP275520","article-title":"Failure to expand the motor unit size to compensate for declining motor unit numbers distinguishes sarcopenic from non-sarcopenic older men","volume":"596","author":"Piasecki","year":"2018","journal-title":"J. Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1113\/JP273895","article-title":"Early structural and functional signature of 3-day human skeletal muscle disuse using the dry immersion model","volume":"595","author":"Demangel","year":"2017","journal-title":"J. Physiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1152\/japplphysiol.00799.2015","article-title":"Fourteen days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle-aged adults","volume":"120","author":"English","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/NEN.0000000000000032","article-title":"Long-Term High-Level Exercise Promotes Muscle Reinnervation with Age","volume":"73","author":"Mosole","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1172\/JCI128411","article-title":"Neuromuscular junctions are stable in patients with cancer cachexia","volume":"130","author":"Boehm","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"10425","DOI":"10.1038\/s41598-019-46929-8","article-title":"Metabolomic Analysis of Skeletal Muscle in Aged Mice","volume":"9","author":"Uchitomi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/jcsm.12360","article-title":"Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism","volume":"10","author":"Pin","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/jbmr.4102","article-title":"Gene-Metabolite Network Linked to Inhibited Bioenergetics in Association With Spaceflight-Induced Loss of Male Mouse Quadriceps Muscle","volume":"35","author":"Chakraborty","year":"2020","journal-title":"J. Bone Miner. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13575\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:07Z","timestamp":1760169067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,17]]},"references-count":150,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413575"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413575","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,17]]}}}