Experimental gerontology最新文献

{"title":"Gut microbial signatures for aging-related sarcopenia and dietary links among community-dwelling old-old adults: A metagenomic study.","authors":"Ting Zhang, Shuyi Li, Yafei Wu, Jason Leung, Hui Jiang, Zhilu Xu, Siew C Ng, Timothy Kwok","doi":"10.1016/j.exger.2026.113161","DOIUrl":"https://doi.org/10.1016/j.exger.2026.113161","url":null,"abstract":"<p><strong>Background and objectives: </strong>Sarcopenia, characterized by progressive loss of muscle mass, strength and function, poses a major aging-related health challenge. While a gut-muscle axis is implicated, microbiota-sarcopenia associations in the old-old (≥80 years) remain unexplored.</p><p><strong>Methods: </strong>This cross-sectional analysis included 315 community-dwelling adults aged ≥80 years from a longitudinal cohort at the 20-year follow-up timepoint, of whom 180 met the inclusion criteria. Gut microbiota was profiled by shotgun metagenomic sequencing alongside sarcopenia assessment. Microbial taxa associated with sarcopenia were identified using MaAsLin2, and dietary associations were assessed by partial Spearman correlation.</p><p><strong>Results: </strong>The prevalence of sarcopenia in this old-old cohort (mean age 86.8 ± 4.3 years) was 51.7%. Sarcopenic individuals showed lower nutrition scores, reduced microbial richness and altered β-diversity (all P < 0.05). Multivariable analysis identified six differentially abundant species associated with sarcopenia (FDR < 0.10), including two positively associated (Ruthenibacterium lactatiformans and Catenibacillus scindens), and four negatively associated (Phascolarctobacterium faecium, Pyramidobacter piscolens, Lacrimispora saccharolytica and Limosilactobacillus mucosae). Random forest and LEfSe analysis validated R. lactatiformans and P. faecium as the most discriminative signatures for sarcopenia. After adjusting for obesity, these signatures remained significant (P < 0.05). These alterations were linked to functional dysregulation, including increased purine degradation and reduced biotin biosynthesis potential. R. lactatiformans abundance negatively correlated with dietary maltose intake (P < 0.05).</p><p><strong>Conclusion: </strong>In old-old adults, we identified distinct gut microbiota signatures associated with sarcopenia. R. lactatiformans and P. faecium emerged as candidate features. The dietary-microbiota correlations suggest potential nutrition strategies. These findings provide a basis for exploring microbiota-based approaches in advanced aging.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"113161"},"PeriodicalIF":4.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857274","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":"Serum and plasma glial fibrillary acidic protein in patients with schizophrenia: A systematic review and meta-analysis.","authors":"Rasoul Ebrahimi, Mehra Fekri, Shakiba Salarvandian, Farzin Tahmasbi Arashlow, Shokoofe Noori","doi":"10.1016/j.exger.2026.113155","DOIUrl":"https://doi.org/10.1016/j.exger.2026.113155","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is a neurodevelopmental disorder with a progressive course that typically begins in late adolescence or early adulthood. Glial fibrillary acidic protein (GFAP), a key component of the astrocyte cytoskeleton, has been linked to schizophrenia, with abnormal GFAP levels observed in both brain tissue and peripheral blood samples. This study aims to systematically review and meta-analyze GFAP levels in schizophrenia patients to assess its potential as a biomarker of astrocytic damage.</p><p><strong>Methods: </strong>We systematically searched PubMed, Scopus, and Web of Science up to April 23, 2025, for studies reporting blood GFAP levels in patients with schizophrenia and healthy controls. Eligible studies included human participants, with GFAP measured in serum or plasma and results reported as summary statistics or extractable from graphs. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Effect sizes were calculated using Hedges' g. Due to high heterogeneity (I² > 50%), a random effects model was applied. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated through funnel plots and Egger's and Begg's tests.</p><p><strong>Results: </strong>A total of 164 records were identified through database searches. After removing duplicates, 118 records were screened based on title and abstract, and 12 studies underwent full-text screening. Eight studies were ultimately included. The studies included 854 participants, with an age range from 24 to 45 years. GFAP levels in schizophrenia patients were significantly higher compared to healthy controls (SMD = 0.74, 95% CI [0.15, 1.33], p = 0.01; I² = 93.68%). Removing two specific studies one at a time rendered the results insignificant, while excluding other studies individually did not affect significance. Publication bias was suggested by Begg's test and Egger's test (p < 0.05). Quality assessment indicated low risk of bias in most domains, though most of the studies had high risk due to insufficient reporting on patient enrollment and blinding of laboratory technicians.</p><p><strong>Discussion: </strong>Our findings suggest a significant difference in GFAP levels in patients with schizophrenia and indicate a potential role for GFAP in astrocytic pathology in these patients. Nonetheless, additional well-designed studies with larger sample sizes and rigorous methodologies are still needed to fully clarify its clinical relevance.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"113155"},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847656","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":"Feasibility and acceptability of remote ischemic conditioning combined with low-intensity resistance training in older adults with mobility impairments: A randomized controlled pilot trial protocol.","authors":"Stephanie Milosovic, Andrew Albright, Tiffany Hilton, Natanael Casiano-Agosto, Senthil Selvaraj, J Kyle Covington, Catherine Lang, Sarah Peskoe, Xin Zhang, Cathleen Colon-Emeric, William Todd Cade","doi":"10.1016/j.exger.2026.113158","DOIUrl":"https://doi.org/10.1016/j.exger.2026.113158","url":null,"abstract":"<p><strong>Background: </strong>Rehabilitation outcomes in older individuals with mobility impairments are often suboptimal due to limited capacity for high-intensity exercise. Remote ischemic conditioning is a low-cost, non-invasive technique that may enhance physiological adaptations to exercise.</p><p><strong>Objective: </strong>To assess the feasibility and acceptability of combining remote ischemic conditioning with low-intensity resistance exercise training in older individuals with mobility impairments, and to evaluate the feasibility of collecting plasma biomarkers.</p><p><strong>Design: </strong>A randomized, blocked feasibility trial with n = 20 participants aged ≥65 years with mobility impairment, comparing high-dose remote ischemic conditioning with low-intensity resistance exercise training versus low-dose remote ischemic conditioning with low-intensity resistance exercise training over a 6-week intervention period.</p><p><strong>Methods: </strong>Participants will undergo baseline and post-intervention assessments, including body composition, muscle strength, physical function, vascular function, exercise tolerance, and acceptability, resilience, and quality of life questionnaires. Blood samples will be collected pre- and post-remote ischemic conditioning and exercise sessions for the quantification of plasma lactate, cytokines, growth factors, oxidative stress, vascular health, and extracellular vesicles.</p><p><strong>Outcomes: </strong>Primary outcomes include feasibility (recruitment, retention, adherence) and acceptability (interviews, questionnaires) of the intervention. Secondary outcomes include the feasibility of biomarker collection and collecting physical activity, physical function, muscle strength and mass, exercise tolerance, quality of life, resilience, vascular function, and biomarker outcomes over the course of the study intervention.</p><p><strong>Conclusion: </strong>This pilot study aims to inform the design of a larger clinical trial by evaluating the feasibility of a novel remote ischemic conditioning with low-intensity resistance exercise training intervention and identifying responsive outcome measures.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"113158"},"PeriodicalIF":4.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847742","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":"Effects of body composition on age- and sex-related differences in resting metabolic rate from a healthy aging cohort","authors":"Marcos Moliné ,&nbsp;Stephanie R. Heimler ,&nbsp;Jaclyn Bergstrom ,&nbsp;Lina Scandalis ,&nbsp;David Wing ,&nbsp;Daniel Moreno ,&nbsp;Howard J. Phang ,&nbsp;Anthony J.A. Molina","doi":"10.1016/j.exger.2026.113084","DOIUrl":"10.1016/j.exger.2026.113084","url":null,"abstract":"<div><div>Resting metabolic rate (RMR) accounts for the majority of the total energy expenditure. While RMR is known to decline with advancing age and is recognized to be lower in females compared to males, the mechanisms underlying these differences remain unclear. Changes in body composition are posited to account for age- and sex-related differences in RMR, but to what extent lacks consensus. We characterized 80 healthy adults aged 23–82 years from the San Diego Nathan Shock Center (SD-NSC) clinical cohort for body composition and RMR using dual-energy x-ray absorptiometry (DXA) and indirect calorimetry techniques, respectively. Body composition metrics—body surface area (BSA), lean tissue mass (LTM), and total body fat (TBF)—were modelled as predictive variables to assess their explanatory power against the age and sex effects on RMR. We found that the negative association between RMR and age persists even after adjusting for body composition and sex, with a predicted decrease in RMR per decade of 62.6 kcal/day (ꞵ = −62.6, <em>P</em> &lt; 0.0001). While individual body composition metrics do not account for the observed sex differences in RMR, adjusting for all body composition metrics together explained the observation that females have lower RMR compared to males. Our results suggest that while differences in body composition can explain sex differences in RMR, additional factors independent of body composition contribute to age-related differences. These results provide new insights into RMR differences among healthy individuals across the human life-course, which may inform age-appropriate interventions for optimizing metabolism.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"217 ","pages":"Article 113084"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319114","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":"Changes in human multifidus muscle size with aging and short-term disuse","authors":"Fabio Sarto ,&nbsp;Elena Monti ,&nbsp;Sara Tagliaferri ,&nbsp;Bostjan Simunič ,&nbsp;Marco Salvi ,&nbsp;Tereza Jandova ,&nbsp;Martino V. Franchi ,&nbsp;Rado Pišot ,&nbsp;Marcello Maggio ,&nbsp;Marco V. Narici","doi":"10.1016/j.exger.2026.113090","DOIUrl":"10.1016/j.exger.2026.113090","url":null,"abstract":"<div><div>Lumbar multifidus (MF) muscle plays a key role in spinal stability, yet its adaptations to aging and disuse, which become increasingly prevalent with advancing age, remain unclear. We conducted two studies to investigate age- and inactivity-induced changes in MF size. In Study 1, we assessed 32 young adults (50% females) and 75 older adults (67% females), categorized as non-sarcopenic (NS) or probable sarcopenic (PS) based on EWGSOP2 criteria. In Study 2, we examined early MF responses to 10-day horizontal bed rest in 10 young males. MF cross-sectional area (CSA) and side-to-side asymmetry were measured using ultrasound imaging and compared with the vastus lateralis (VL) CSA. In Study 1, MF CSA was negatively associated with age (<em>p</em> &lt; 0.0001) and probable sarcopenia, being lower in PS compared to NS (<em>p</em> = 0.012). MF showed larger effect sizes than VL [Y vs NS: MF g = 1.62, VL g = 1.35; Y vs PS: MF g = 2.48, VL g = 1.35]. MF asymmetry was greater in PS compared to Y (<em>p</em> = 0.003). In Study 2, bed rest induced early reductions in MF CSA (detectable by day 4, <em>p</em> = 0.047) without increasing asymmetry. In conclusion, the MF was smaller in older populations and decreased following short-term disuse, while greater asymmetry was observed only with aging. These findings suggest that the MF is a highly plastic muscle in response to aging and disuse and that its assessment may serve as a potential hallmark of muscle maladaptation in clinical and experimental settings.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"217 ","pages":"Article 113090"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388389","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":"Pain duration as a staging variable: A conceptual framework for testing depression-pathway interventions in dementia risk","authors":"Herul Wahyudin ,&nbsp;Maria Oktasari ,&nbsp;Bagus Julian Hikmy ,&nbsp;Ma'rifatin Indah Kholili ,&nbsp;Hayu Stevani ,&nbsp;Raudah Zaimah Dalimunthe","doi":"10.1016/j.exger.2026.113089","DOIUrl":"10.1016/j.exger.2026.113089","url":null,"abstract":"<div><div>This study proposes a conceptual framework for testing the role of pain duration as a staging variable in the relationship between chronic pain and dementia risk. Chronic pain duration, often associated with an increased risk of dementia, may influence how depression interacts with cognitive decline. In this article, we propose two hypotheses for future research: (H1) In the 3–24 months period, depression-targeted care through interventions such as cognitive behavioral therapy and antidepressant medication is expected to provide the most significant cognitive benefits. (H2) After 24 months, depression care remains important, but its effectiveness may be limited without multimodal pain management, which includes physical therapy and pharmacological interventions. We also consider confounding variables such as comorbidities and sociodemographic factors that may influence study outcomes, which need to be accounted for in future research. This framework aims to provide a foundation for longitudinal research and intervention trials that test the proposed hypotheses, contributing to the development of more effective dementia prevention strategies for individuals with chronic pain.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"217 ","pages":"Article 113089"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388461","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":"Genetic associations and mediating effects of insulin resistance between hypertension and sarcopenia: A bidirectional two-sample Mendelian randomization study","authors":"Jingfeng Zou ,&nbsp;Liyin Zhang ,&nbsp;Shaotian Li ,&nbsp;Shanshan Hu ,&nbsp;Chunhui Tian ,&nbsp;Yiting Liu ,&nbsp;Yilan Yin ,&nbsp;Mi Yan ,&nbsp;Guqiao Nie ,&nbsp;Wen Peng","doi":"10.1016/j.exger.2026.113086","DOIUrl":"10.1016/j.exger.2026.113086","url":null,"abstract":"<div><h3>Objective</h3><div>Hypertension and sarcopenia are major global public health problems among the aging society. This study aims to explore the causal associations and mediating effects of insulin resistance (IR) between hypertension and sarcopenia.</div></div><div><h3>Methods</h3><div>A bidirectional two-step Mendelian randomization (MR) was applied to determine the causal mediating role of IR in the pathway between hypertension and four sarcopenia related traits (right and left handgrip strength/HGS, Appendicular lean mass/ALM, and Usual walking pace/UWP) by using single nucleotide polymorphisms as instrumental variables to predict insulin, body mass index (BMI), fasting blood glucose (FBG), glycosylated hemoglobin a1c (HbA1c) and triglycerides (TG) genetically.</div></div><div><h3>Results</h3><div>The IVW analysis indicated that there was a suggestive causality between hypertension and a reduced risk of UWP (OR = 0.952, 95% CI 0.913–0.991, <em>P</em> = 0.018), with triglycerides mediating a moderate proportion of this effect (6.985–13.666%).No significant causal associations were found between hypertension and right HGS, left HGS, or ALW (all <em>P</em> &gt; 0.05). Each 1-standard deviation decrease in genetically determined right HGS (OR 0.963, 95% CI 0.935–0.992, <em>P</em> = 0.013) increased the suggestive risk of hypertension, each 1-standard deviation decrease in genetically determined left HGS (OR 0.958, 95% CI 0.930–0.986, <em>P</em> = 0.004), and ALM (OR 0.977, 95% CI 0.969–0.986, <em>P</em> = 0.000) also increased the risk of hypertension. No significant causal association was found between UWP and hypertension (<em>P</em> &gt; 0.05). Compared with other indicators, insulin, strongly associated with the link between right HGS, left HGS, ALM and hypertension, has gained the notably total proportion mediated effect accounted from 11.378 to 21.297%. Furthermore, we systematically summarized the pathogenesis between hypertension and sarcopenia.</div></div><div><h3>Conclusion</h3><div>The study indicates the causality between hypertension and sarcopenia, potentially mediated by insulin resistance (BMI, insulin, FBG, HbA1c, and TG). It provides crucial evidence for the genetic association between hypertension and sarcopenia, while also offering insights for managing both conditions, particularly in terms of blood glucose, lipid, and weight control.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"217 ","pages":"Article 113086"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370618","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":"Exploration of the co-regulatory mechanism of calorie restriction and endurance exercise on elderly skeletal muscle and its potential intervention targets","authors":"Donghui Zhu ,&nbsp;Xiuxiu Chen","doi":"10.1016/j.exger.2026.113083","DOIUrl":"10.1016/j.exger.2026.113083","url":null,"abstract":"<div><div>This study aims to explore the shared transcriptomic features of caloric restriction (CR) and endurance exercise in skeletal muscle among older adults. As age increases, muscle atrophy gradually becomes a common issue of functional decline in the elderly. Utilizing bioinformatics analysis, this research identified 101 overlapping differentially expressed genes (DEGs) involved in both CR and endurance exercise. These genes are primarily enriched in key biological pathways related to longevity, Apelin signaling, AMPK signaling, FoxO signaling, and cGMP-PKG signaling pathways. Additionally, we identified 10 key genes (such as LPL, PPARGC1A, and IGF1), 4 transcription factors (FOXC1, POU2F2, GATA2, and STAT3), and 4 microRNAs (miR-155-5p, miR-124-3p, miR-1-3p, and miR-16-5p) interacting with these genes. Drug-gene interaction analysis identified carotuximab as a compound with potential relevance for future investigation in the context of muscle aging. These findings provide new insights into the molecular mechanisms underlying muscle functional decline in the elderly and propose potential targets and drugs for intervention development.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"217 ","pages":"Article 113083"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373694","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":"Metformin attenuates lens epithelial cell senescence by suppressing cGAS-STING via SIRT1-PGC-1α-mediated mitochondrial fission.","authors":"Jialin Luo, Chaoqun Wei, Liyao Sun, Huirui Liu, Yu Mi, Qi An, Chen Yang, Xiaohan Yu, Zijian Yu, Hongyan Ge","doi":"10.1016/j.exger.2026.113157","DOIUrl":"https://doi.org/10.1016/j.exger.2026.113157","url":null,"abstract":"<p><p>UVB-induced lens epithelial cell (LEC) senescence is among the important factors involved in the pathogenesis of age-related cataract (ARC). This study aimed to investigate the anti-aging effect of metformin (Met) and to elucidate the molecular mechanisms underlying this effect. RNA sequencing, nontargeted metabolomics analysis and network pharmacology were conducted. The expression of senescence indicators (P53 and P21^Cip1) and senescence-associated β-galactosidase (SA-β-gal) activity were assessed. Mitochondrial function and dynamics were evaluated by measuring the mitochondrial membrane potential (MMP), transmission electron microscope (TEM), and Western blotting. Cytosolic mtDNA was visualized by fluorescence staining, and the activation of the SIRT1-PGC-1α pathway and the cGAS-STING pathway were analysed by Western blotting. Our findings indicated that cellular senescence was predominantly responsible for UVB-induced cataract. Met attenuated UVB-induced cataract by inhibiting the senescence phenotype. Mechanistically, Met activated the SIRT1-PGC-1α pathway to inhibit mitochondrial fragmentation. This attenuation of mitochondrial fragmentation reduced mtDNA release into the cytosol, thereby inhibiting the activation of the cGAS-STING-mediated LEC senescence. Our findings on the efficacy of Met pave the way for the development of new pharmacological strategies to prevent cataract development.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"219 ","pages":"113157"},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824946","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":"Exploration of ferroptosis-related biomarkers and regulatory mechanisms in two diseases (sarcopenia and idiopathic pulmonary fibrosis) based on transcriptome and machine learning.","authors":"Jun Yang, Kaihua Zhou, Xiaojian He, Ke Rong","doi":"10.1016/j.exger.2026.113150","DOIUrl":"10.1016/j.exger.2026.113150","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia (SP) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases, but share ferroptosis-related biomarkers and their regulatory mechanisms in both remain unclear, hindering targeted research and therapy.</p><p><strong>Methods: </strong>In this study, ferroptosis-related genes (FeRGs), as well as training sets and test sets related to SP and IPF, were obtained from public databases. After the identification of disease-related differentially expressed genes (DEGs), DEGs shared by SP and IPF were obtained through intersection (genes with consistent DEG change trends across each disease) and union analyses. These shared DEGs were then intersected with FeRGs to obtain candidate genes. Machine learning algorithms and the Wilcoxon rank-sum test were used to confirm the biomarkers, and nomograms were constructed and evaluated. Meanwhile, in-depth studies such as functional enrichment, immune infiltration, drug prediction, and molecular docking were conducted on the biomarkers.</p><p><strong>Results: </strong>Initially, a total of 26 candidate genes were identified. After screening, DDIT4 and MGST1 were identified as ferroptosis-related biomarkers shared by the two diseases, and both were significantly upregulated in the SP and IPF groups. The area under the curve values of the constructed nomograms were 0.91 (for SP) and 0.79 (for IPF), respectively. The p-values of the Hosmer-Lemeshow test for the calibration curves (0.856 and 0.205) were both >0.05, and the DCA showed good performance. The two biomarkers showed differences in enriched pathways. A total of 5 differential immune cells shared by the two diseases were identified, and the biomarkers participated in immune regulation by targeting specific immune cells. Good binding activity (Vina Score < -5.0) was observed between Trichostatin A and both biomarkers.</p><p><strong>Conclusion: </strong>DDIT4 and MGST1 were shared ferroptosis-related biomarkers for SP and IPF. Nomograms enabled reliable prediction, and trichostatin A was a potential targeted drug. These findings supported mechanistic research and targeted therapy for both diseases.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"113150"},"PeriodicalIF":4.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792959","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}