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慢性低度炎症与肌少症
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Abstract:
肌少症目前被普遍认为是老年综合症的一种，其主要表现为出现与增龄相关的肌肉质量减少、肌肉功能和肌肉力量下降。可以导致衰弱、跌倒、骨折、代谢性疾病等发病率和死亡的风险增高。其发病机制复杂，目前仍未完全阐明。在其多种可能机制中，慢性低度炎症被认为是肌少症的关键发病机制。炎性因子直接或间接地通过不同的病理生理过程导致肌少症的发生。反应机体炎症情况的肿瘤坏死因子α、IL-6、CRP、IL-15、IL-10、鸢尾素等多种炎症指标以及血常规中白细胞、血小板、中性粒细胞、淋巴细胞、单核细胞及其衍生物与老年人躯体功能、肌肉力量、肌肉质量等密切相关。这些都可能通过调节氧化应激、蛋白质合成与代谢平衡、细胞周期阻滞、骨骼肌再生、细胞凋亡等途径导致骨骼肌损伤，从而导致肌少症。本文将综述目前肌少症与慢性低度炎症之间的关系研究进展。
Sarcopenia is currently widely considered as a type of geriatric syndrome, characterized by age-related decrease in muscle mass, muscle function, and muscle strength. It can lead to increased risks of weakness, falls, fractures, metabolic diseases, and mortality. The pathogenesis of sarcopenia is complex and not yet fully understood. Among its various possible mechanisms, chronic low-grade inflammation is considered as a key pathogenic mechanism. Inflammatory factors directly or indirectly contribute to the development of sarcopenia through various pathophysiological processes. Inflammatory markers such as tumor necrosis factor-α, IL-6, CRP, IL-15, IL-10, and irisin, as well as white blood cells, platelets, neutrophils, lymphocytes, monocytes, and their derivatives in routine blood tests, are closely related to physical function, muscle strength, and muscle mass in older adults. These factors may lead to skeletal muscle damage and subsequently sarcopenia by regulating oxidative stress, protein synthesis and metabolic balance, cell cycle arrest, skeletal muscle regeneration, and cell apoptosis pathways. This review summarizes the current research progress on the relationship between sarcopenia and chronic low-grade inflammation.
| [1] | Cruz-Jentoft, A.J., Baeyens, J.P., Bauer, J.M., Boirie, Y., Cederholm, T., Landi, F., et al. (2010) Sarcopenia: European consensus on definition and diagnosis. Age and Ageing, 39, 412-423. https://doi.org/10.1093/ageing/afq034 |
| [2] | Lee, J.S.W., Auyeung, T., Kwok, T., Lau, E.M.C., Leung, P. and Woo, J. (2007) Associated Factors and Health Impact of Sarcopenia in Older Chinese Men and Women: A Cross-Sectional Study. Gerontology, 53, 404-410. https://doi.org/10.1159/000107355 |
| [3] | Shock, N.W. (1970) Physiologie Aspects of Aging. Journal of the American Dietetic Association, 56, 491-496. https://doi.org/10.1016/s0002-8223(21)13351-6 |
| [4] | Rosenberg, I.H. (1997) Sarcopenia: Origins and Clinical Relevance. The Journal of Nutrition, 127, 990S-991S. https://doi.org/10.1093/jn/127.5.990s |
| [5] | Fielding, R.A., Vellas, B., Evans, W.J., Bhasin, S., Morley, J.E., Newman, A.B., et al. (2011) Sarcopenia: An Undiagnosed Condition in Older Adults. Current Consensus Definition: Prevalence, Etiology, and Consequences. International Working Group on Sarcopenia. Journal of the American Medical Directors Association, 12, 249-256. https://doi.org/10.1016/j.jamda.2011.01.003 |
| [6] | Chen, L., Liu, L., Woo, J., Assantachai, P., Auyeung, T., Bahyah, K.S., et al. (2014) Sarcopenia in Asia: Consensus Report of the Asian Working Group for Sarcopenia. Journal of the American Medical Directors Association, 15, 95-101. https://doi.org/10.1016/j.jamda.2013.11.025 |
| [7] | Harris, T. (1997) Muscle Mass and Strength: Relation to Function in Population Studies. The Journal of Nutrition, 127, 1004S-1006S. https://doi.org/10.1093/jn/127.5.1004s |
| [8] | Zhou, X., Wu, X. and Zhang, D. (2023) Prevalence of Sarcopenia and Associated Dietary Factors among Older Chinese Adults. Saudi Medical Journal, 44, 1180-1181. https://doi.org/10.15537/smj.2023.44.11.20230371 |
| [9] | 孙丽娜. 2型糖尿病合并肌少症的发生机制及临床价值[D]: [博士学位论文]. 石家庄: 河北医科大学, 2023. |
| [10] | Schaap, L.A., Pluijm, S.M.F., Deeg, D.J.H. and Visser, M. (2006) Inflammatory Markers and Loss of Muscle Mass (Sarcopenia) and Strength. The American Journal of Medicine, 119, 526.E9-526.E17. https://doi.org/10.1016/j.amjmed.2005.10.049 |
| [11] | Gabay, C. and Kushner, I. (1999) Acute-Phase Proteins and Other Systemic Responses to Inflammation. New England Journal of Medicine, 340, 448-454. https://doi.org/10.1056/nejm199902113400607 |
| [12] | Wolf, D. and Ley, K. (2019) Immunity and Inflammation in Atherosclerosis. Circulation Research, 124, 315-327. https://doi.org/10.1161/circresaha.118.313591 |
| [13] | Hotamisligil, G.S. (2006) Inflammation and Metabolic Disorders. Nature, 444, 860-867. https://doi.org/10.1038/nature05485 |
| [14] | Wilson, D., Jackson, T., Sapey, E. and Lord, J.M. (2017) Frailty and Sarcopenia: The Potential Role of an Aged Immune System. Ageing Research Reviews, 36, 1-10. https://doi.org/10.1016/j.arr.2017.01.006 |
| [15] | Olivieri, F., Bonafè, M., Cavallone, L., Giovagnetti, S., Marchegiani, F., Cardelli, M., et al. (2002) The—174 C/G Locus Affects in Vitro/in Vivo IL-6 Production during Aging. Experimental Gerontology, 37, 309-314. https://doi.org/10.1016/s0531-5565(01)00197-8 |
| [16] | Antonicelli, R., Olivieri, F., Bonafè, M., Cavallone, L., Spazzafumo, L., Marchegiani, F., et al. (2005) The Interleukin-6—174 G > C Promoter Polymorphism Is Associated with a Higher Risk of Death After an Acute Coronary Syndrome in Male Elderly Patients. International Journal of Cardiology, 103, 266-271. https://doi.org/10.1016/j.ijcard.2004.08.064 |
| [17] | Lio, D., Scola, L., Crivello, A., Colonna-Romano, G., Candore, G., Bonafè, M., et al. (2002) Gender-Specific Association between—1082 IL-10 Promoter Polymorphism and Longevity. Genes & Immunity, 3, 30-33. https://doi.org/10.1038/sj.gene.6363827 |
| [18] | Lio, D., Scola, L., Crivello, A., Bonafè, M., Franceschi, C., Olivieri, F., et al. (2002) Allele Frequencies of +874T→A Single Nucleotide Polymorphism at the First Intron of Interferon-γ Gene in a Group of Italian Centenarians. Experimental Gerontology, 37, 315-319. https://doi.org/10.1016/s0531-5565(01)00198-x |
| [19] | Castón Osorio, J.J. and Zurbano Go？i, F. (2011) Efectos indirectos de la infección por citomegalovirus. Enfermedades Infecciosas y Microbiología Clínica, 29, 6-10. https://doi.org/10.1016/s0213-005x(11)70050-7 |
| [20] | Antu？a, E., Cachán-Vega, C., Bermejo-Millo, J.C., Potes, Y., Caballero, B., Vega-Naredo, I., et al. (2022) Inflammaging: Implications in Sarcopenia. International Journal of Molecular Sciences, 23, Article 15039. https://doi.org/10.3390/ijms232315039 |
| [21] | Campisi, J. (2011) Cellular Senescence: Putting the Paradoxes in Perspective. Current Opinion in Genetics & Development, 21, 107-112. https://doi.org/10.1016/j.gde.2010.10.005 |
| [22] | Starr, M.E., Evers, B.M. and Saito, H. (2009) Age-associated Increase in Cytokine Production during Systemic Inflammation: Adipose Tissue as a Major Source of Il-6. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 64, 723-730. https://doi.org/10.1093/gerona/glp046 |
| [23] | Morin, C.L., Pagliassotti, M.J., Windmiller, D. and Eckel, R.H. (1997) Adipose Tissue-Derived Tumor Necrosis Factor-Activity Is Elevated in Older Rats. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 52, B190-B195. https://doi.org/10.1093/gerona/52a.4.b190 |
| [24] | Kern, P.A., Ranganathan, S., Li, C., Wood, L. and Ranganathan, G. (2001) Adipose Tissue Tumor Necrosis Factor and Interleukin-6 Expression in Human Obesity and Insulin Resistance. American Journal of Physiology-Endocrinology and Metabolism, 280, E745-E751. https://doi.org/10.1152/ajpendo.2001.280.5.e745 |
| [25] | Paris, M.T., Bell, K.E. and Mourtzakis, M. (2020) Myokines and Adipokines in Sarcopenia: Understanding Cross-Talk between Skeletal Muscle and Adipose Tissue and the Role of Exercise. Current Opinion in Pharmacology, 52, 61-66. https://doi.org/10.1016/j.coph.2020.06.003 |
| [26] | Fabbri, M., Paone, A., Calore, F., Galli, R. and Croce, C.M. (2013) A New Role for Micrornas, as Ligands of Toll-Like Receptors. RNA Biology, 10, 169-174. https://doi.org/10.4161/rna.23144 |
| [27] | Pinti, M., Cevenini, E., Nasi, M., De Biasi, S., Salvioli, S., Monti, D., et al. (2014) Circulating Mitochondrial DNA Increases with Age and Is a Familiar Trait: Implications for “Inflamm-Aging”. European Journal of Immunology, 44, 1552-1562. https://doi.org/10.1002/eji.201343921 |
| [28] | Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., et al. (2010) Circulating Mitochondrial Damps Cause Inflammatory Responses to Injury. Nature, 464, 104-107. https://doi.org/10.1038/nature08780 |
| [29] | Heintz, C. and Mair, W. (2014) You Are What You Host: Microbiome Modulation of the Aging Process. Cell, 156, 408-411. https://doi.org/10.1016/j.cell.2014.01.025 |
| [30] | Mueller, S., Saunier, K., Hanisch, C., Norin, E., Alm, L., Midtvedt, T., et al. (2006) Differences in Fecal Microbiota in Different European Study Populations in Relation to Age, Gender, and Country: A Cross-Sectional Study. Applied and Environmental Microbiology, 72, 1027-1033. https://doi.org/10.1128/aem.72.2.1027-1033.2006 |
| [31] | Biagi, E., Nylund, L., Candela, M., Ostan, R., Bucci, L., Pini, E., et al. (2010) Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians. PLOS ONE, 5, e10667. https://doi.org/10.1371/journal.pone.0010667 |
| [32] | Biagi, E., Candela, M., Turroni, S., Garagnani, P., Franceschi, C. and Brigidi, P. (2013) Ageing and Gut Microbes: Perspectives for Health Maintenance and Longevity. Pharmacological Research, 69, 11-20. https://doi.org/10.1016/j.phrs.2012.10.005 |
| [33] | Churchward-Venne, T.A., Breen, L. and Phillips, S.M. (2013) Alterations in Human Muscle Protein Metabolism with Aging: Protein and Exercise as Countermeasures to Offset Sarcopenia. BioFactors, 40, 199-205. https://doi.org/10.1002/biof.1138 |
| [34] | Schiaffino, S., Dyar, K.A., Ciciliot, S., Blaauw, B. and Sandri, M. (2013) Mechanisms Regulating Skeletal Muscle Growth and Atrophy. The FEBS Journal, 280, 4294-4314. https://doi.org/10.1111/febs.12253 |
| [35] | Bodine, S.C. and Baehr, L.M. (2014) Skeletal Muscle Atrophy and the E3 Ubiquitin Ligases Murf1 and Mafbx/Atrogin-1. American Journal of Physiology-Endocrinology and Metabolism, 307, E469-E484. https://doi.org/10.1152/ajpendo.00204.2014 |
| [36] | Perry, B.D., Caldow, M.K., Brennan-Speranza, T.C., et al. (2016) Muscle Atrophy in Patients with Type 2 Diabetes Mellitus: Roles of Inflammatory Pathways, Physical Activity and Exercise. Exercise Immunology Review, 22, 94-109. |
| [37] | Xia, Z., Cholewa, J., Zhao, Y., Shang, H., Yang, Y., Araújo Pess？a, K., et al. (2017) Targeting Inflammation and Downstream Protein Metabolism in Sarcopenia: A Brief Up-Dated Description of Concurrent Exercise and Leucine-Based Multimodal Intervention. Frontiers in Physiology, 8, Article 434. https://doi.org/10.3389/fphys.2017.00434 |
| [38] | Scharner, J. and Zammit, P.S. (2011) The Muscle Satellite Cell at 50: The Formative Years. Skeletal Muscle, 1, Article No. 28. https://doi.org/10.1186/2044-5040-1-28 |
| [39] | Yin, H., Price, F. and Rudnicki, M.A. (2013) Satellite Cells and the Muscle Stem Cell Niche. Physiological Reviews, 93, 23-67. https://doi.org/10.1152/physrev.00043.2011 |
| [40] | Bouché, M., Mu？oz-Cánoves, P., Rossi, F. and Coletti, D. (2014) Inflammation in Muscle Repair, Aging, and Myopathies. BioMed Research International, 2014, Article ID: 821950. https://doi.org/10.1155/2014/821950 |
| [41] | Tidball, J.G. and Wehling-Henricks, M. (2006) Macrophages Promote Muscle Membrane Repair and Muscle Fibre Growth and Regeneration during Modified Muscle Loading in Mice in Vivo. The Journal of Physiology, 578, 327-336. https://doi.org/10.1113/jphysiol.2006.118265 |
| [42] | Reidy, P.T., McKenzie, A.I., Mahmassani, Z.S., Petrocelli, J.J., Nelson, D.B., Lindsay, C.C., et al. (2019) Aging Impairs Mouse Skeletal Muscle Macrophage Polarization and Muscle-Specific Abundance during Recovery from Disuse. American Journal of Physiology-Endocrinology and Metabolism, 317, E85-E98. https://doi.org/10.1152/ajpendo.00422.2018 |
| [43] | Villalta, S.A., Rinaldi, C., Deng, B., Liu, G., Fedor, B. and Tidball, J.G. (2010) Interleukin-10 Reduces the Pathology of mdx Muscular Dystrophy by Deactivating M1 Macrophages and Modulating Macrophage Phenotype. Human Molecular Genetics, 20, 790-805. https://doi.org/10.1093/hmg/ddq523 |
| [44] | Dalle, S., Rossmeislova, L. and Koppo, K. (2017) The Role of Inflammation in Age-Related Sarcopenia. Frontiers in Physiology, 8, Article 1045. https://doi.org/10.3389/fphys.2017.01045 |
| [45] | Torrente, Y., Fahime, E.E., Caron, N.J., Del Bo, R., Belicchi, M., Pisati, F., et al. (2003) Tumor Necrosis Factor-α (TNF-α) Stimulates Chemotactic Response in Mouse Myogenic Cells. Cell Transplantation, 12, 91-100. https://doi.org/10.3727/000000003783985115 |
| [46] | Chen, S., Jin, B. and Li, Y. (2007) TNF-α Regulates Myogenesis and Muscle Regeneration by Activating P38 MAPK. American Journal of Physiology-Cell Physiology, 292, C1660-C1671. https://doi.org/10.1152/ajpcell.00486.2006 |
| [47] | Reid, M.B. and Li, Y. (2001) Tumor Necrosis Factor-α and Muscle Wasting: A Cellular Perspective. Respiratory Research, 2, Article No. 269. https://doi.org/10.1186/rr67 |
| [48] | Haddad, F., Zaldivar, F., Cooper, D.M. and Adams, G.R. (2005) Il-6-induced Skeletal Muscle Atrophy. Journal of Applied Physiology, 98, 911-917. https://doi.org/10.1152/japplphysiol.01026.2004 |
| [49] | O’Leary, M.F., Wallace, G.R., Bennett, A.J., Tsintzas, K. and Jones, S.W. (2017) IL-15 Promotes Human Myogenesis and Mitigates the Detrimental Effects of TNFα on Myotube Development. Scientific Reports, 7, Article No. 12997. https://doi.org/10.1038/s41598-017-13479-w |
| [50] | Cantini, M., Massimino, M.L., Rapizzi, E., Rossini, K., Catani, C., Dallalibera, L., et al. (1995) Human Satellite Cell-Proliferation in Vitro Is Regulated by Autocrine Secretion of IL-6 Stimulated by a Soluble Factor(s) Released by Activated Monocytes. Biochemical and Biophysical Research Communications, 216, 49-53. https://doi.org/10.1006/bbrc.1995.2590 |
| [51] | Tezze, C., Romanello, V. and Sandri, M. (2019) FGF21 as Modulator of Metabolism in Health and Disease. Frontiers in Physiology, 10, Article 419. https://doi.org/10.3389/fphys.2019.00419 |
| [52] | Shokri-mashhadi, N., Moradi, S., Heidari, Z. and Saadat, S. (2021) Association of Circulating C-Reactive Protein and High-Sensitivity C-Reactive Protein with Components of Sarcopenia: A Systematic Review and Meta-Analysis of Observational Studies. Experimental Gerontology, 150, Article ID: 111330. https://doi.org/10.1016/j.exger.2021.111330 |
| [53] | Tuttle, C.S.L., Thang, L.A.N. and Maier, A.B. (2020) Markers of Inflammation and Their Association with Muscle Strength and Mass: A Systematic Review and Meta-Analysis. Ageing Research Reviews, 64, Article ID: 101185. https://doi.org/10.1016/j.arr.2020.101185 |
| [54] | Yalcin, A., Silay, K., Balik, A.R., Avcio？lu, G. and Aydin, A.S. (2017) The Relationship between Plasma Interleukin-15 Levels and Sarcopenia in Outpatient Older People. Aging Clinical and Experimental Research, 30, 783-790. https://doi.org/10.1007/s40520-017-0848-y |
| [55] | Couper, K.N., Blount, D.G. and Riley, E.M. (2008) IL-10: The Master Regulator of Immunity to Infection. The Journal of Immunology, 180, 5771-5777. https://doi.org/10.4049/jimmunol.180.9.5771 |
| [56] | Steen, E.H., Wang, X., Balaji, S., Butte, M.J., Bollyky, P.L. and Keswani, S.G. (2020) The Role of the Anti-Inflam-matory Cytokine Interleukin-10 in Tissue Fibrosis. Advances in Wound Care, 9, 184-198. https://doi.org/10.1089/wound.2019.1032 |
| [57] | Bostr？m, P., Wu, J., Jedrychowski, M.P., Korde, A., et al. (2012) A PGC1-α-Dependent Myokine That Drives Brown-Fat-Like Development of White Fat and Thermogenesis. Nature, 481, 463-468. |
| [58] | Bostr？m, P., Wu, J., Jedrychowski, M.P., Korde, A., Ye, L., Lo, J.C., et al. (2012) A Pgc1-Α-Dependent Myokine That Drives Brown-Fat-Like Development of White Fat and Thermogenesis. Nature, 481, 463-468. https://doi.org/10.1038/nature10777 |
| [59] | Zhao, M., Zhou, X., Yuan, C., Li, R., Ma, Y. and Tang, X. (2020) Association between Serum Irisin Concentrations and Sarcopenia in Patients with Liver Cirrhosis: A Cross-Sectional Study. Scientific Reports, 10, Article No. 16093. https://doi.org/10.1038/s41598-020-73176-z |
| [60] | Chang, J.S., Kim, T.H., Nguyen, T.T., Park, K., Kim, N. and Kong, I.D. (2017) Circulating Irisin Levels as a Predictive Biomarker for Sarcopenia: A Cross-sectional Community-Based Study. Geriatrics & Gerontology International, 17, 2266-2273. https://doi.org/10.1111/ggi.13030 |
| [61] | Borges, T.C., Gomes, T.L., Pichard, C., Laviano, A. and Pimentel, G.D. (2021) High Neutrophil to Lymphocytes Ratio Is Associated with Sarcopenia Risk in Hospitalized Cancer Patients. Clinical Nutrition, 40, 202-206. https://doi.org/10.1016/j.clnu.2020.05.005 |
| [62] | Zhao, W., Zhang, Y., Hou, L., Xia, X., Ge, M., Liu, X., et al. (2021) The Association between Systemic Inflammatory Markers and Sarcopenia: Results from the West China Health and Aging Trend Study (WCHAT). Archives of Gerontology and Geriatrics, 92, Article ID: 104262. https://doi.org/10.1016/j.archger.2020.104262 |
| [63] | Yoshida, Y., Iwasa, H., Kim, H. and Suzuki, T. (2022) Association between Neutrophil-To-Lymphocyte Ratio and Physical Function in Older Adults: A Community-Based Cross-Sectional Study in Japan. International Journal of Environmental Research and Public Health, 19, Article 8996. https://doi.org/10.3390/ijerph19158996 |
| [64] | ？ztürk, Z.A., Kul, S., Türkbeyler, ？.H., Say？ner, Z.A. and Abiyev, A. (2018) Is Increased Neutrophil Lymphocyte Ratio Remarking the Inflammation in Sarcopenia? Experimental Gerontology, 110, 223-229. https://doi.org/10.1016/j.exger.2018.06.013 |
| [65] | Park, W., Jung, D., Lee, J., Shim, J. and Kwon, Y. (2018) Association of Platelet Count with Sarcopenic Obesity in Postmenopausal Women: A Nationwide Population-Based Study. Clinica Chimica Acta, 477, 113-118. https://doi.org/10.1016/j.cca.2017.12.004 |
| [66] | Gholizade, M., Farhadi, A., Marzban, M., Mahmudpour, M., Nabipour, I., Kalantarhormozi, M., et al. (2022) Association between Platelet, White Blood Cell Count, Platelet to White Blood Cell Ratio and Sarcopenia in Community-Dwelling Older Adults: Focus on Bushehr Elderly Health (BEH) Program. BMC Geriatrics, 22, Article No. 300. https://doi.org/10.1186/s12877-022-02954-3 |
| [67] | Tang, T., Xie, L., Tan, L., Hu, X. and Yang, M. (2020) Inflammatory Indexes Are Not Associated with Sarcopenia in Chinese Community-Dwelling Older People: A Cross-Sectional Study. BMC Geriatrics, 20, Article No. 457. https://doi.org/10.1186/s12877-020-01857-5 |
