Rejuvenation research最新文献

{"title":"Biochemical and Physiological Response During Oxidative Stress: A Cross-Species Perspective.","authors":"Dharmsheel Shrivastav, Juhi Mishra, Varun Kumar Sharma, Shilpy Singh, Mohammad Idreesh Khan, Saleh A Alsanie, Fauzia Ashafaq, Mirza Masroor Ali Beg","doi":"10.1177/15491684251386712","DOIUrl":"https://doi.org/10.1177/15491684251386712","url":null,"abstract":"<p><p>Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, is a fundamental challenge affecting both invertebrate and vertebrate organisms. Environmental triggers such as pollutants, heavy metals, pesticides, and seasonal fluctuations, alongside endogenous factors like heme metabolism and disease, contribute to elevated ROS production across animal taxa. These molecular species can damage proteins, membranes, and nucleic acids, compromising cellular integrity and function. The aim of this study is to comprehensively observe and compare the impact of oxidative stress on invertebrates (including protozoa, annelids, arthropods, and mollusks) and vertebrates (fish, amphibians, birds, and mammals), elucidating common and distinct stress pathways. Using integrative evidence from schematic representations and biological pathways, this work highlights conserved mechanisms such as lipid peroxidation, Fenton chemistry, and the upregulation of defense enzymes. Despite evolutionary divergence, the findings demonstrate that oxidative stress responses are universally pivotal in regulating cellular homeostasis, inflammation, and survival. The study underscores the importance of redox balance in animal adaptation and health, offering insight into stress physiology and potential targets for mitigating oxidative damage in diverse species.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of Dietary Bioactive Peptides in Treating Alzheimer's Disease and Mild Cognitive Impairment by Network Pharmacology and Molecular Docking Analysis.","authors":"Ruirui Li, Jing Zi, Yifan Hu, Xinlong Li, Qianqian Cao, Yanliu Li, Xiaoyu Wang, Jingyuan Xiong, Guo Cheng","doi":"10.1089/rej.2024.0092","DOIUrl":"10.1089/rej.2024.0092","url":null,"abstract":"<p><p>Emerging evidence suggests that bioactive peptides from various foods have therapeutic potentials in improving cognitive function in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We aimed to explore the characteristics of these peptides and their mechanisms on AD/MCI using a network pharmacology approach. We compiled a dataset of cognition-enhancing peptides from literatures and identified shared targets between these peptides and AD/MCI using Swiss Target Predication, PharmMapper, OMIM, GeneCards, TTD, and Drugbank databases. We then performed functional enrichment analysis and constructed a gene-gene interaction network to identify key hub targets. Additionally, we investigated the transcription factors (TFs) and microRNAs (miRNAs) regulating these hub genes. Molecular docking and dynamic simulations were performed using AutoDock Vina and GROMACS. We identified 59 cognition-enhancing oligopeptides, typically short and rich in arginine. These peptides were predicted to interact with 222 potential targets relevant to AD/MCI, with functional pathways mainly involving neuroactive ligand-receptor interactions and inflammation. We identified 15 hub targets, regulated by 144 TFs and 95 miRNAs. Notably, peptides containing the \"Trp-Tyr\" sequence demonstrated strong binding affinities to many hub targets, especially matrix metalloproteinase-9. The findings provided valuable insights into the molecular mechanisms through which bioactive peptides may act against AD/MCI and highlight the potential of network pharmacology for future exploration of bioactive peptides from natural foods.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"205-216"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moxibustion's Impact on Ferroptosis Regulation: A Key to Relieving Inflammatory Injury in Rheumatoid Arthritis.","authors":"Tiancheng Wang, Chuanyu Peng, Dong Gao, Chuanying Zhang, Feng Hao, Lu He","doi":"10.1089/rej.2024.0110","DOIUrl":"10.1089/rej.2024.0110","url":null,"abstract":"<p><p>To study the mechanism through which moxibustion alleviates inflammatory injury of synovial tissue in rheumatoid arthritis (RA) rats model by determining moxibustion's effect on ferroptosis regulation by the tumor suppressor protein p53 and solute carrier family 7 member 11 (SLC7A11). Rats were developed as RA models by the administration of Freund's complete adjuvant. In the corresponding groups, moxibustion treatment was carried out using cigarette-like moxa strips that were suspended near \"Shenshu\" (BL23) and \"Zusanli\" (ST36) once daily for 15 days, and the p53 agonist NSC59984 was administered intraperitoneally. After 15 days of treatment, histomorphological changes were noted by transmission electron microscopy; p53, glutathione peroxidase 4 (GPX4), and SLC7A11 expression were detected by Western blot; serum levels of reactive oxygen species (ROS), glutathione (GSH), and Fe²⁺ were estimated with the colorimetric and fluorescent probe methods; and serum levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) were quantified by enzyme linked immunosorbent assay. Compared with the model group and agonist group, the mitochondrial damage in the moxibustion and moxibustion + agonist groups were showed varying degrees of reduction. The levels of p53, ROS, Fe²⁺, TNF-α, and IL-1β in the model group were significantly higher than those in the normal group, the agonist group was significantly higher than the model group, and the moxibustion and moxibustion + agonists groups were lower than the model and agonist groups. The levels of SLC7A11, GPX4, and GSH were the opposite. Moxibustion can improve RA synovial inflammatory injury by regulating ferroptosis through inhibition of p53 protein expression.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"217-225"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating Causal Relationships Among Gut Microbiota, Human Blood Metabolites, and Knee Osteoarthritis: Evidence from a Two-Stage Mendelian Randomization Analysis.","authors":"Zhen Wang, Chi Zhao, Zheng Wang, Mengmeng Li, Lili Zhang, Jieyao Diao, Juntao Chen, Lijuan Zhang, Yu Wang, Miaoxiu Li, Yunfeng Zhou, Hui Xu","doi":"10.1089/rej.2024.0079","DOIUrl":"10.1089/rej.2024.0079","url":null,"abstract":"<p><p><b><i>Background:</i></b> Although previous observational studies suggest a potential association between gut microbiota (GM) and knee osteoarthritis (KOA), the causal relationships remain unclear, particularly concerning the role of blood metabolites (BMs) as potential mediators. Elucidating these interactions is crucial for understanding the mechanisms underlying KOA progression and may inform the development of novel therapeutic strategies. <b><i>Objective:</i></b> This study aimed to determine the causal relationship between GM and KOA and to quantify the potential mediating role of BMs. <b><i>Methods:</i></b> Instrumental variables (IVs) for GM and BMs were retrieved from the MiBioGen consortium and metabolomics genome-wide association studies (GWAS) databases. KOA-associated single-nucleotide polymorphisms were sourced from the FinnGen consortium. Inverse-variance weighted approach was utilized as the main analytical method for Mendelian randomization (MR) analysis, complemented by MR-Egger, simple mode, weighted mode, and weighted median methods. The causal relationships between GM, BMs, and KOA were sequentially analyzed by multivariate MR. False discovery rate correction was applied to account for multiple comparisons in the MR results. Sensitivity analyses and reverse MR analysis were also conducted to verify the reliability of the findings. Finally, a two-step approach was employed to determine the proportion of BMs mediating the effects of GM on KOA. <b><i>Results:</i></b> MR analysis identified seven gut microbial species that are causally associated with KOA. Additionally, MR analysis of 1091 BMs and 309 metabolite ratios revealed 13 metabolites that influence the risk of KOA. Through two-step analysis, three BMs were identified as mediators of the effects of two GMs on KOA. Among them, 6-hydroxyindole sulfate exhibited the highest mediation percentage (10.26%), followed by <i>N</i>-formylanthranilic acid (6.55%). Sensitivity and reverse causality analyses further supported the robustness of these findings. <b><i>Conclusion:</i></b> This research identified specific GMs and BMs that have a causal association with KOA. These findings provide critical insights into how GM may influence KOA risk by modulating specific metabolites, which could be valuable for the targeted treatment and prevention of KOA.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"239-247"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F-box/WD Repeat-Containing Protein 5 Promotes Breast Cancer Progression by Regulating Ferroptosis via Enhancing Krüppel-like Factor 13 Ubiquitination Through Phosphoinositide 3-Kinase/Serine/Threonine Protein Kinase Pathway.","authors":"Chen Chen, Hui Li, Ziyi Zhang, Haipeng Li, Hongtao Li","doi":"10.1089/rej.2024.0111","DOIUrl":"10.1089/rej.2024.0111","url":null,"abstract":"<p><p>Breast cancer (BC) is a prevalent malignancy among women. Evidence has indicated that F-box/WD repeat-containing protein 5 (FBXW5) is crucial in oncogenesis and progression. However, the function of FBXW5 in BC remains elusive. This work aims to explore the regulatory mechanisms of FBXW5 in the development of BC. The expression of FBXW5 in pan-cancer and breast invasive carcinoma (BRCA) was analyzed using The Cancer Genome Atlas (TCGA) database. FBXW5 level was enhanced in BC tissues. Besides, FBXW5 inhibition significantly decreased cell viability by 49.05% in MDA-MB-231 cells and 62.30% in MCF-7 cells. FBXW5 inhibition significantly inhibited cell proliferation by 66% in MDA-MB-231 cells and 74% in MCF-7 cells. FBXW5 inhibition significantly suppressed cell migration by 77.2% in MDA-MB-231 cells and 82.15% in MCF-7 cells. FBXW5 inhibition significantly inhibited cell invasion by 64.14% in MDA-MB-231 cells and 71.33% in MCF-7 cells. In vivo, FBXW5 depletion reduced tumor weight by 63.39% and tumor volume by 65.17%. Moreover, FBXW5 silencing restrained lung metastases <i>in vivo</i>. Besides, the impact of FBXW5 on the malignant behavior of BC cells was mediated through the regulation of ferroptosis. Mechanically, FBXW5 facilitated Kruppel-like factor 13 (KLF13) degradation by enhancing its ubiquitination. The addition of FBXW5 facilitated cell proliferation, migration, and invasion and inhibited ferroptosis in MDA-MB-231 and MCF-7 cells, which were neutralized by KLF13 overexpression. Besides, the knockdown of KLF13 led to the activation of the PI3K/AKT pathway. KLF13 silencing counteracted the inhibitory effects of FBXW5 depletion on cell proliferation, migration, and invasion, as well as its promotion of ferroptosis, effects that were reversed by LY294002. In conclusion, targeting FBXW5 may serve as a potential therapeutic strategy for BC by modulating the KLF13/PI3K/AKT axis.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"226-238"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of External Therapies of Traditional Chinese Medicine in Patients with Knee Osteoarthritis: A Systematic Review and Network Meta-Analysis.","authors":"Zhen Wang, Chi Zhao, Mengmeng Li, Lili Zhang, Jieyao Diao, Yiming Wu, Tao Yang, Mingwei Shi, Yang Lei, Yu Wang, Miaoxiu Li, Yanqin Bian, Yunfeng Zhou, Hui Xu","doi":"10.1089/rej.2025.0039","DOIUrl":"10.1089/rej.2025.0039","url":null,"abstract":"<p><p>The use of external therapies for knee osteoarthritis (KOA) in traditional Chinese medicine (TCM) is supported by several guidelines and systematic reviews. However, the relative advantages and disadvantages of TCM external therapies and their mechanisms of action have not yet been confirmed in evidence-based medicine. We used network meta-analysis to rank the effectiveness and safety of TCM external therapies, screen the optimal TCM external therapies. TCM external therapies for KOA published before October 2024 were comprehensively retrieved from eight electronic databases. Using the Cochrane Reviewers' Handbook, two independent reviewers performed study selection, data extraction, and bias assessment of the included randomized controlled trials (RCTs). Data analysis was conducted using Stata 16.0 and RevMan 5.4 software. A total of 68 RCTs were identified, including 6571 participants, involving 11 interventions, 4.41% of which showed a high risk of bias. The results of the network meta-analysis revealed that in terms of improving Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scores, each external therapy was better than conventional medicine. Electroacupuncture may be the most effective intervention in improving the VAS score and TNF-α level. Moxibustion resulted in the greatest improvement in WOMAC function and IL-6 levels. The most effective interventions for reducing WOMAC pain scores were the manual needle knife, followed by electroacupuncture and Tuina therapy (SUCRA = 82.9%, 79.0%, and 71.4%, respectively). Warming acupuncture dominantly increased Lysholm scores. The safety results showed that the three safest interventions were the sham intervention, Tuina therapy, and moxibustion (SUCRA = 90.6%, 83.1%, and 68.8%, respectively). Silver needle had the best comprehensive effect. Electroacupuncture has the best effect on improving pain symptoms, and moxibustion can be prioritized when functional limitations are the main symptoms. To some extent, the changes in inflammatory factors correlated with an improvement in KOA symptoms.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"248-262"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of the Geriatric Nutritional Risk Index on Postoperative Cognitive Dysfunction and Complications after Total Hip Arthroplasty Under General Anesthesia: A Retrospective Study.","authors":"Xia Li, Yunyun Sun, Liang Chen, Yuanhai Li","doi":"10.1177/15491684251379234","DOIUrl":"https://doi.org/10.1177/15491684251379234","url":null,"abstract":"<p><p>The Geriatric Nutritional Risk Index (GNRI) is widely used to assess nutritional status. However, its association with postoperative cognitive dysfunction (POCD) and postoperative complications in elderly patients receiving total hip arthroplasty remains inadequately explored. GNRI was calculated based on serum albumin and body weight. POCD was diagnosed using the Z-score method based on cognitive test performance on the seventh postoperative day. Glial fibrillary acidic protein (GFAP) and S100β levels were determined using an enzyme-linked immunosorbent assay. A Receiver Operating Characteristic curve was performed to evaluate the predictive value of GNRI. Multivariate logistic regression was conducted to identify risk factors for POCD in elderly patients undergoing total hip arthroplasty. The POCD group was significantly older, had lower educational attainment, longer surgery duration, greater intraoperative blood loss, and lower preoperative GNRI scores compared to the non-POCD group. Preoperative GNRI demonstrated moderate predictive value for POCD, with an area under curve (AUC) of 0.78. Multivariate logistic regression analysis identified age (odds ratio [OR]: 1.214, 95% confidence interval [CI]: 1.047-1.449), blood loss (OR: 1.198, 95% CI: 1.055-1.493), and anesthesia duration (OR: 1.376, 95% CI: 1.112-1.795) as significant risk factors for POCD, while preoperative GNRI (OR: 0.885, 95% CI: 0.768-0.973) was identified as a protective factor. POCD patients exhibited significantly lower Montreal Cognitive Assessment (MoCA) scores and higher serum S100β and GFAP levels than the non-POCD group. Preoperative GNRI was positively correlated with MoCA scores (r = 0.46, <i>p</i> < 0.001) and negatively correlated with serum S100β (r = -0.43, <i>p</i> < 0.001) and GFAP (r = -0.37, <i>p</i> < 0.001) levels. Higher preoperative GNRI scores were associated with a reduced incidence of postoperative complications, including pulmonary infections and liver dysfunction. Preoperative GNRI serves as an effective predictor of POCD and postoperative complications in elderly patients receiving hip arthroplasty.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of COVID-19 Isolation on Sarcopenia in Older Adults: A Cohort Study from Taiwan.","authors":"Pu-Jun Fang, Ping-Hsuan Kuo, Tung-Wei Kao, Tao-Chun Peng","doi":"10.1177/15491684251381561","DOIUrl":"https://doi.org/10.1177/15491684251381561","url":null,"abstract":"<p><p>Previous studies on sarcopenia and COVID-19 have primarily focused on pathophysiological mechanisms, leaving the effects of social isolation policies largely unexplored. Taiwan offers a unique environment to investigate this issue. This study investigates the association between COVID-19-related isolation and sarcopenia in older adults in Taiwan. Participants aged 65 and older were enrolled from annual geriatric health check-ups conducted between 2018 and 2023. The years from 2018 to 2020 were designated as the pre-COVID-19 period, while 2022-2023 was considered the post-COVID-19 era. Demographic data and health conditions were collected. The assessments encompassed body composition, muscle strength, and physical performance. The prevalence and trends of sarcopenia were analyzed. The prevalence of low muscle strength declined in 2021 but subsequently increased from 2022 to 2023 (<i>p</i>_quadratic = 0.018). In 2023, compared with 2018-2020, the odds ratio for sarcopenia and severe sarcopenia was 1.3 (95% confidence interval [CI] 1.01-1.67), and the odds ratio for low physical performance was 1.73 (95% CI 1.39-2.15). This is the first report describing the association between COVID-19 pandemic-related policies and the prevalence of sarcopenia, revealing a significant increase in sarcopenia prevalence following the pandemic. Our results emphasize the necessity of tailored strategies to support older adults during and after health crises.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Inhibits Pancreatic Cancer Progression by Regulating CDC42 Succinylation and Disrupting the Extracellular Matrix.","authors":"Mengde Ding, Qian Wang","doi":"10.1177/15491684251379251","DOIUrl":"https://doi.org/10.1177/15491684251379251","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is a highly lethal malignancy with significant drug resistance and recurrence. This study explores the molecular mechanisms by which resveratrol (RES) inhibits PC proliferation, invasion, and migration, aiming to provide new insights for future therapeutic strategies. Network pharmacology was used to construct a component-pathway-target network diagram for the effect of RES on PC. Transwell assays were used to analyze cell invasion. In addition, scratch assays were conducted to evaluate cell migration ability, and qPCR was utilized to monitor the mRNA expression levels of genes. Immunofluorescence and Western blotting were applied to detect protein expression. The results demonstrate that RES exhibits a significant inhibitory effect on PC cells at different concentrations, with 50 μmol/L RES showing the most pronounced inhibition. This observation was further confirmed by Transwell and scratch assays, which showed that RES significantly inhibits PC cell proliferation, invasion, and migration. Network pharmacology analysis suggests that RES may act on the Rap1 pathway to suppress the progression of PC. <i>In vitro</i> experiments confirmed that RES downregulates the expression of CDC42, MMP2, and MMP9. Notably, immunoprecipitation experiments revealed that RES induces the succinylation of CDC42, which, in turn, inhibits the CDC42 signaling pathway. This disruption leads to the destabilization of the extracellular matrix (ECM), thereby impeding tumor progression. This study demonstrates that RES significantly inhibits the proliferation, invasion, and migration of PC cells by mediating the succinylation of CDC42, which in turn inhibits the CDC42 signaling pathway and disrupts the dynamics of the ECM. This mechanism highlights the potential of RES as an anticancer agent and provides new insights for the development of therapeutic strategies for PC.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of CD127 on CD28⁺ CD45RA⁺ CD8^br Treg Cells in Mediating the Association Between GDF-15 and Sarcopenia.","authors":"Yangqi Pan, Peng Zheng, Tao Yao, Zi Tao, Luoxiang Fang, Jiafeng Lin","doi":"10.1177/15491684251378963","DOIUrl":"https://doi.org/10.1177/15491684251378963","url":null,"abstract":"<p><p>Growth Differentiation Factor 15 (GDF-15) is closely associated with the occurrence and progression of sarcopenia, but the causal relationship between GDF-15 and sarcopenia remains unclear, and it is also uncertain whether immune cells mediate the pathway between GDF-15 and sarcopenia. We employed Mendelian randomization analysis to explore the causal relationship between GDF-15 and sarcopenia, using the inverse variance-weighted (IVW) method as the primary analytical approach, and validated the results through sensitivity analyses. In addition, we explored whether 731 immune cell phenotypes mediate these causal relationships. GDF-15 was negatively correlated with all four traits of sarcopenia, specifically with whole body fat-free mass (odds ratio [OR] = 0.989, 95% confidence interval [CI] = 0.979-0.998, <i>p</i>_IVW = 2.149E-02), left arm fat-free mass (OR = 0.988, 95% CI = 0.979-0.998, <i>p</i>_IVW = 1.345E-02), right arm fat-free mass (OR = 0.987, 95% CI = 0.979-0.995, <i>p</i>_IVW = 1.091E-03), and appendicular lean mass (OR = 0.984, 95% CI = 0.974-0.993, <i>p</i>_IVW = 7.658E-04). Mediation analysis indicated that CD127 on CD28⁺ CD45RA⁺ CD8^br mediated the causal relationship between GDF-15 and sarcopenia, with a mediation proportion of 21.58% (<i>p</i> = 0.023). In conclusion, our study proposed that CD127 on CD28⁺ CD45RA⁺ CD8^br mediates the causal relationship between GDF-15 and sarcopenia, providing potential theoretical support and practical guidance for the innovation of treatment strategies and personalized therapies for sarcopenia.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}