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Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention
Open accessAbstract
Background: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. Methods: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured. Results: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05). Conclusions: High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.
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“Under pathological conditions, TWEAK also becomes overexpressed and activates the NF‐κB pathway via the FGF‐inducible 14 receptors, leading to increased expression of MuRF1 and activation of the ubiquitin‐proteasome (UPS) pathway as well.[ 69 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [69]
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“Cytokines such as TNF‐α, TNF‐like weak promoter of apoptosis (TWEAK), IL‐18, and IL‐6, are thought to induce muscle atrophy during sarcopenia.[ 69 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [69]
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“Intensive lifestyle interventions lasting 12 weeks (three times a week), including whey supplementation and resistance exercise, can significantly lower the leptin level, restore metabolic hormone levels, and ameliorate muscle mass in sarcopenic patients [85].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [85]
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Metadata
- Authors
- Li, C., Yu, K., Shyh‐Chang, N., Li, G., Jiang, L., Yu, S., Xu, L., Liu, R., Guo, Z., Xie, H., Li, R., Ying, J., Li, K., & Li, D.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Chinese Academy of Sciences (CN)
- Department of General Surgery and Clinical Nutrition TianJin Union Medical Center Hongqiao District Tianjin China
- Department of Central Laboratory Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Dongcheng District Beijing China
- Department of Clinical Laboratory Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Dongcheng District Beijing China
- Department of Health Care Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Dongcheng District Beijing China
- Department of Clinical Nutrition and Department of Health Medicine Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Dongcheng District Beijing China
- Corresponding author
- Yu, Kang
- Shyh‐Chang, Ng
- Venue
- Journal of Cachexia, Sarcopenia and Muscle
- Publisher
- Wiley
- Published
- 2019-04-10
- Volume
- 10
- Issue
- 3
- Pages
- 586-600
- ISSN
- 2190-5991 (ISSN-L)
- 2190-6009
- PMC
- PMC6596393
- OpenAlex
- W2938744410
- Cited by
- 280
- References
- 54
- Citations by year
- 2026: 26 · 2025: 46 · 2024: 54 · 2023: 71 · 2022: 41 · 2021: 25 · 2020: 17
- FWCI
- 14.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese Academy of Sciences (XDA16020301, KJZD-SW-L04)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- sarcopenia, aging, inflammatory cytokines, TWEAK, TNF-α, interleukin-6, IL-18, leptin, insulin-like growth factor I, adiponectin, whey protein supplementation, resistance training, lifestyle intervention, older adults, muscle mass, subclinical inflammation, type 2 diabetes, metabolic hormones, sarcopenia risk
- MeSH terms
- Healthy Lifestyle, Cytokine TWEAK, Aged, Aging, Body Composition, China, Cross-Sectional Studies, Female, Humans, Inflammation, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Severity of Illness Index, Tumor Necrosis Factor-alpha, Treatment Outcome, Muscle, Skeletal, Inflammation Mediators, Resistance Training, Sarcopenia
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