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A Mendelian randomization study reveals TNF-β as a potential protective factor against sarcopenia.

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Title: A Mendelian randomization study reveals TNF-β as a potential protective factor against sarcopenia.
Authors: Mei Z; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China., Wan Y; Department of Stomatology, No. 903 Hospital of PLA, Hangzhou, China., Mao X; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China., Qi W; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China., Zhou G; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China., Chen M; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China., Li X; Department of Orthopaedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China.; Shanghai University of Traditional Chinese Medicine, Shanghai, China., Pan H; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China., Wang D; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Source: Medicine [Medicine (Baltimore)] 2026 Oct 02; Vol. 105 (40), pp. e50951.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 2985248R Publication Model: Print Cited Medium: Internet ISSN: 1536-5964 (Electronic) Linking ISSN: 00257974 NLM ISO Abbreviation: Medicine (Baltimore) Subsets: MEDLINE
Imprint Name(s): Original Publication: Hagerstown, Md : Lippincott Williams & Wilkins
MeSH Terms: Sarcopenia*/genetics , Sarcopenia*/blood , Lymphotoxin-alpha*/genetics , Lymphotoxin-alpha*/blood , Mendelian Randomization Analysis*, Inflammation/genetics ; Hand Strength/physiology ; Humans ; Protective Factors
Abstract: Sarcopenia, defined by the loss of muscle mass and strength, significantly impacts the elderly and is linked to chronic inflammation. The exact causal relationship between circulating inflammatory factors and sarcopenia is not yet clear. We employed a 2-sample Mendelian randomization analysis using 91 circulating inflammatory factors as exposures and 4 sarcopenia traits as outcomes to explore potential causality. Our analysis confirmed a significant causal association between circulating inflammatory factors and sarcopenia. Specifically, tumor necrosis factor-beta was significantly associated with all sarcopenia traits (appendicular lean mass: P < .001, odds ratio [OR] = 1.023; left grip strength: P < .001, OR = 1.010; right grip strength: P = .001, OR = 1.008; walking pace: P = .017, OR = 1.004), supported by Bonferroni correction and multiple sensitivity analyses. Tumor necrosis factor-beta has emerged as a critical protective factor for sarcopenia, suggesting that targeting its levels may influence treatment approaches. This study emphasized the role of inflammatory pathways in sarcopenia and demonstrated the utility of Mendelian randomization in identifying these associations.
(Copyright © 2026 the Author(s). Published by Wolters Kluwer Health, LLC.)
Competing Interests: The authors have no conflicts of interest to declare.
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Stem Cell Res Ther. 2016 Mar 22;7:44. (PMID: 27006071)
Adv Exp Med Biol. 2018;1088:267-279. (PMID: 30390256)
Diabetol Metab Syndr. 2018 Apr 03;10:25. (PMID: 29632617)
Nat Immunol. 2023 Sep;24(9):1540-1551. (PMID: 37563310)
Front Immunol. 2024 Mar 01;15:1330386. (PMID: 38495887)
Cell Metab. 2016 Apr 12;23(4):675-84. (PMID: 27076079)
Lymphokine Res. 1990 Winter;9(4):491-7. (PMID: 1708843)
Int Immunol. 2013 Jul;25(7):397-403. (PMID: 23657002)
Metabolism. 2023 Jul;144:155533. (PMID: 36907247)
IUBMB Life. 2015 Feb;67(2):88-97. (PMID: 25850692)
Cytokine Growth Factor Rev. 2003 Dec;14(6):523-35. (PMID: 14563354)
Med Sci Monit. 2006 Jul;12(7):RA121-4. (PMID: 16810143)
Acta Neuropathol. 2000 Nov;100(5):521-7. (PMID: 11045674)
Annu Rev Immunol. 1988;6:407-38. (PMID: 3289572)
BMC Public Health. 2023 Jul 24;23(1):1416. (PMID: 37488531)
Autoimmunity. 2002 Sep;35(6):377-80. (PMID: 12568117)
Trends Genet. 2022 Apr;38(4):353-363. (PMID: 34991903)
Stat Methods Med Res. 2012 Jun;21(3):223-42. (PMID: 21216802)
Age Ageing. 2019 Jan 1;48(1):16-31. (PMID: 30312372)
Nature. 2015 Jul 9;523(7559):158. (PMID: 26156365)
Eur J Phys Rehabil Med. 2013 Feb;49(1):131-43. (PMID: 23575207)
J Am Coll Cardiol. 2022 Mar 1;79(8):837-847. (PMID: 35210039)
Ageing Res Rev. 2020 Dec;64:101185. (PMID: 32992047)
Lancet. 2019 Jun 29;393(10191):2636-2646. (PMID: 31171417)
Curr Opin Immunol. 1992 Jun;4(3):327-32. (PMID: 1329840)
Exp Gerontol. 2021 Jul 15;150:111330. (PMID: 33848566)
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Arthritis Res Ther. 2013;15(6):R202. (PMID: 24283517)
Nature. 2017 Feb 8;542(7640):177-185. (PMID: 28179656)
Nutrients. 2024 Feb 24;16(5):. (PMID: 38474762)
Maturitas. 2017 Feb;96:10-15. (PMID: 28041587)
Physiol Rev. 2019 Jan 1;99(1):115-160. (PMID: 30354964)
Stroke Vasc Neurol. 2017 Apr 21;2(2):47-52. (PMID: 28959491)
Cell. 2010 Mar 19;140(6):883-99. (PMID: 20303878)
J Gastroenterol. 2019 Oct;54(10):845-859. (PMID: 31392488)
Cureus. 2022 Jan 4;14(1):e20917. (PMID: 35145813)
Grant Information: LBY24H290004 Zhejiang Provincial Natural Science Foundation of China under Grant; LQN25H270019 Zhejiang Provincial Natural Science Foundation of China under Grant; 2024-XK-57 Key Discipline of Traditional Chinese Medicine in Zhejiang Province; 2025HZZD16 The Construction Fund of Key Medical Discipline of Hangzhou
Contributed Indexing: Keywords: Mendelian randomization; TNF-β; inflammatory factors; sarcopenia
Substance Nomenclature: 0 (Lymphotoxin-alpha)
Entry Date(s): Date Created: 20261002 Date Completed: 20261002 Latest Revision: 20261005
Update Code: 20261005
PubMed Central ID: PMC13632991
DOI: 10.1097/MD.0000000000050951
PMID: 42826314
Database: MEDLINE
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  Data: A Mendelian randomization study reveals TNF-β as a potential protective factor against sarcopenia.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Mei+Z%22&quot;&gt;Mei Z&lt;/searchLink&gt;; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wan+Y%22&quot;&gt;Wan Y&lt;/searchLink&gt;; Department of Stomatology, No. 903 Hospital of PLA, Hangzhou, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Mao+X%22&quot;&gt;Mao X&lt;/searchLink&gt;; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Qi+W%22&quot;&gt;Qi W&lt;/searchLink&gt;; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhou+G%22&quot;&gt;Zhou G&lt;/searchLink&gt;; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Chen+M%22&quot;&gt;Chen M&lt;/searchLink&gt;; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+X%22&quot;&gt;Li X&lt;/searchLink&gt;; Department of Orthopaedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China.; Shanghai University of Traditional Chinese Medicine, Shanghai, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Pan+H%22&quot;&gt;Pan H&lt;/searchLink&gt;; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wang+D%22&quot;&gt;Wang D&lt;/searchLink&gt;; Department of Orthopaedics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
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  Data: Sarcopenia, defined by the loss of muscle mass and strength, significantly impacts the elderly and is linked to chronic inflammation. The exact causal relationship between circulating inflammatory factors and sarcopenia is not yet clear. We employed a 2-sample Mendelian randomization analysis using 91 circulating inflammatory factors as exposures and 4 sarcopenia traits as outcomes to explore potential causality. Our analysis confirmed a significant causal association between circulating inflammatory factors and sarcopenia. Specifically, tumor necrosis factor-beta was significantly associated with all sarcopenia traits (appendicular lean mass: P &amp;lt; .001, odds ratio [OR] = 1.023; left grip strength: P &amp;lt; .001, OR = 1.010; right grip strength: P = .001, OR = 1.008; walking pace: P = .017, OR = 1.004), supported by Bonferroni correction and multiple sensitivity analyses. Tumor necrosis factor-beta has emerged as a critical protective factor for sarcopenia, suggesting that targeting its levels may influence treatment approaches. This study emphasized the role of inflammatory pathways in sarcopenia and demonstrated the utility of Mendelian randomization in identifying these associations.&lt;br /&gt; (Copyright &#169; 2026 the Author(s). Published by Wolters Kluwer Health, LLC.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: The authors have no conflicts of interest to declare.
– Name: Ref
  Label: References
  Group: RefInfo
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  Data: LBY24H290004 Zhejiang Provincial Natural Science Foundation of China under Grant; LQN25H270019 Zhejiang Provincial Natural Science Foundation of China under Grant; 2024-XK-57 Key Discipline of Traditional Chinese Medicine in Zhejiang Province; 2025HZZD16 The Construction Fund of Key Medical Discipline of Hangzhou
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        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Protective Factors
        Type: general
      – SubjectFull: Sarcopenia genetics
        Type: general
      – SubjectFull: Sarcopenia blood
        Type: general
      – SubjectFull: Lymphotoxin-alpha genetics
        Type: general
      – SubjectFull: Lymphotoxin-alpha blood
        Type: general
      – SubjectFull: Mendelian Randomization Analysis
        Type: general
    Titles:
      – TitleFull: A Mendelian randomization study reveals TNF-β as a potential protective factor against sarcopenia.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Mei Z
      – PersonEntity:
          Name:
            NameFull: Wan Y
      – PersonEntity:
          Name:
            NameFull: Mao X
      – PersonEntity:
          Name:
            NameFull: Qi W
      – PersonEntity:
          Name:
            NameFull: Zhou G
      – PersonEntity:
          Name:
            NameFull: Chen M
      – PersonEntity:
          Name:
            NameFull: Li X
      – PersonEntity:
          Name:
            NameFull: Pan H
      – PersonEntity:
          Name:
            NameFull: Wang D
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 02
              M: 10
              Text: 2026 Oct 02
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1536-5964
          Numbering:
            – Type: volume
              Value: 105
            – Type: issue
              Value: 40
          Titles:
            – TitleFull: Medicine
              Type: main
ResultId 1