Rejuvenation research最新文献

{"title":"Regenerative Strategies for Myocardial Infarction and Their Present Clinical Application.","authors":"Joana Marie C Cruz, Jose B Nevado, Javier Lozano-Gerona, Al James A Manua, Mariel Lizbeth Joy S Agsaoay, Jana Victoria B San Pedro, Dencee Jean T Ledesma, Alexandrea Beatriz G Manangan, Ahmad Reza Mazahery","doi":"10.1177/15491684261496118","DOIUrl":"https://doi.org/10.1177/15491684261496118","url":null,"abstract":"<p><p>Early revascularization and contemporary medical management for myocardial infarction (MI) have significantly improved patients' survival and performance. However, despite significant advances in MI therapies, several challenges remain in improving cardiac recovery and optimizing long-term clinical outcomes, including persistent cardiomyocyte loss, adverse ventricular remodeling, and subsequent cardiac complications. These have prompted increasing exploration of regenerative approaches for MI, which focus on repairing, regenerating, and/or replacing damaged myocardial tissue to restore cardiac structure and function. This includes stem cell-based therapies, cell-free approaches, gene therapy, tissue engineering, and blood-based regenerative strategies. While significant progress has been made in both preclinical and clinical studies of these regenerative therapies, further research is required to optimize their therapeutic efficacy. This review provides a summary of the recent advances, clinical progress, and translational limitations of some of the commonly investigated regenerative therapies for MI.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"15491684261496118"},"PeriodicalIF":2.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225549","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 Testing in Indeterminate Thyroid Nodules: Current Evidence, Clinical Utility, and Practical Considerations.","authors":"Tabinda Hasan, Huda Eltayeb, Ghaida S AlSugair, Sridhar Mishra, Mohammad Idreesh Khan, Nidhi Anand","doi":"10.1177/15491684261497857","DOIUrl":"https://doi.org/10.1177/15491684261497857","url":null,"abstract":"<p><p>Indeterminate thyroid nodules classified as Bethesda III (atypia of undetermined significance) and Bethesda IV (follicular neoplasm) remain a diagnostic challenge because cytomorphology alone cannot reliably distinguish benign from malignant disease. Molecular testing has emerged as an adjunct to cytological, sonographic, and clinical assessment to refine preoperative risk stratification and inform management. This narrative review critically summarizes current evidence for major commercially available molecular platforms, including the Afirma Gene Expression Classifier, Afirma Genomic Sequencing Classifier (GSC), ThyroSeq v3, and ThyGeNEXT^®/ThyraMIR^®, with emphasis on diagnostic performance, clinical utility, limitations, and contemporary practice integration. In pivotal validation studies, Afirma GSC demonstrated a sensitivity of 91%, specificity of 68%, positive predictive value (PPV) of 47%, and negative predictive value (NPV) of 96%, whereas ThyroSeq v3 demonstrated a sensitivity of 94%, specificity of 82%, PPV of 66%, and NPV of 97%. In a blinded multicenter validation study of Bethesda III/IV nodules, ThyGeNEXT/ThyraMIR demonstrated prevalence-adjusted sensitivity of 95%, specificity of 90%, PPV of 75%, and NPV of 97% at a standardized disease prevalence of 30%. These estimates should not be interpreted as direct head-to-head comparisons because studies differ in population characteristics, disease prevalence, reference standards, assay generation, and classification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Clinical-utility evidence indicates that molecular testing can influence decisions regarding surveillance and surgery and may reduce potentially avoidable diagnostic operations, although the magnitude of benefit varies across assays and clinical settings. <i>The Bethesda System for Reporting Thyroid Cytopathology</i> supports selective molecular testing when results are expected to meaningfully influence management. Molecular testing should therefore be regarded as an adjunct to integrated risk assessment rather than a stand-alone determinant of management, with results interpreted alongside cytological, sonographic, clinical, patient-specific, and institutional factors.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"15491684261497857"},"PeriodicalIF":2.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198625","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 Association Between Serum Vitamin D and Gait Speed in a Middle-Aged and Older Taiwanese Population: A Community-Based Cross-Sectional Study.","authors":"Chun-Ru Lin, Po-An Tsai, Jing-Yi Chen, Ming-Hao Chen, Wen-Yuan Hsieh, Kuo-Hao Lee, Yun-Hsi Lin, Tsai-Sheng Fu, Po-Liang Lai, Yun-Hsiang Shih, Yu-Lin Shih, Chin-Chuan Shih, Yu-Chung Tsao, Yu-Hsiang Lin, Jau-Yuan Chen","doi":"10.1177/15491684261496120","DOIUrl":"https://doi.org/10.1177/15491684261496120","url":null,"abstract":"<p><p>Gait speed is a key indicator for diagnosing sarcopenia, validated by both the European Working Group on Sarcopenia in Older People in 2018 and the Asian Working Group on Sarcopenia in 2019 for assessing physical performance. While global data link vitamin D to physical performance, regional sex-stratified evidence in East Asian populations remains limited. This study aims to validate and confirm the association between gait speed and vitamin D levels in a middle-aged and older population in Taiwan. This cross-sectional investigation focused on community-dwelling residents. Participants were assigned to vitamin D sufficiency (≥30 ng/mL), insufficiency (<30 ng/mL and ≥ 20 ng/mL), and deficiency (<20 ng/mL) defined by the American Endocrine Society and International Osteoporosis Foundation criteria. Analyses included Student's <i>t-</i>tests, analysis of variance (ANOVA), Chi-square test and sex-stratified multiple linear regression. A total of 396 participants (164 men and 232 women) were recruited, with a mean age of 65.18 ± 8.75 years; mean serum vitamin D concentration of 28.25 ± 9.45 ng/mL; and mean gait speed of 0.91 ± 0.23 m/s. A positive association between gait speed and 25(OH)D (<i>p</i> = 0.047), and a negative association between gait speed and age (<i>p</i> < 0.001) and body mass index (BMI) (<i>p</i> = 0.005) were observed in men. Conversely, in women, gait speed was negatively associated with age (<i>p</i> < 0.001), BMI (<i>p</i> = 0.010), hypertension (<i>p</i> = 0.027), and diabetes mellitus (<i>p</i> = 0.009). This study demonstrated a positive association between gait speed and serum 25(OH)D levels in middle-aged and older men.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"15491684261496120"},"PeriodicalIF":2.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170605","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":"A Machine Learning-Based Fall Risk Prediction Model for Middle-Aged and Older Adults with Comorbid Cardiovascular Disease and Arthritis: Development and Geographic Split-Sample Validation.","authors":"Ying Zhang, Yan Li","doi":"10.1177/15491684261496130","DOIUrl":"https://doi.org/10.1177/15491684261496130","url":null,"abstract":"<p><p>Falls impose a major public health burden on middle-aged and older adults. Coexisting cardiovascular disease (CVD) and arthritis further increases fall risk, yet targeted prediction models remain scarce, especially in Chinese populations. We analyzed 633 China Health and Retirement Longitudinal Study participants aged ≥45 years with comorbid CVD and arthritis at the 2015 baseline. Seven predictors were selected through univariate analysis, LASSO logistic regression (LR), and clinical review. Eight machine-learning algorithms were compared. Among models with an area under the receiver operating characteristic curve (AUC) ≥0.72, the model with the highest specificity was preferred to reduce false-positive referrals. A geographically defined holdout group (<i>n</i> = 110) from different provincial-code regions, but within the same CHARLS source population, was treated as a geographic split-sample rather than independent external validation. Performance was assessed using AUC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1-score, calibration, decision-curve analysis, precision-recall curves, and SHapley Additive exPlanations (SHAP). During cumulative follow-up, 296 participants (46.8%) reported at least one fall. Random forest (RF) and LR achieved similar internal-validation AUCs (0.730 vs. 0.729); RF was selected because of higher specificity. Internally, RF showed 87.5% specificity, 37.7% sensitivity, 70.3% PPV, 64.2% NPV, and an F1-score of 0.491. Its AUC in the geographic holdout sample was 0.735. Despite similar AUCs, sensitivity and specificity differed substantially between samples, suggesting limited regional stability of the fixed threshold. SHAP identified fall history, ankle pain, activities of daily living impairment, and sleep duration as the most influential predictors. The RF model showed moderate discrimination and a conservative, high-specificity profile. However, its low internal sensitivity means it should not be used alone to rule out falls or as a diagnostic tool. Pending independent validation and regional threshold calibration, it may serve only as adjunctive stratification within a stepped assessment pathway and should not replace routine clinical fall-risk screening.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"15491684261496130"},"PeriodicalIF":2.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169500","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 the Mechanism of Action of the Astragalus-Ginseng Herb Pair in Treating Coronary Heart Disease: A Network Pharmacology and Experimental Validation Approach.","authors":"Zhiping Liu, Jia Chen, Tianwei Meng, Boyu Wang, Chengjia Li, Changxing Liu, Yingying Wang","doi":"10.1177/15491684261446288","DOIUrl":"10.1177/15491684261446288","url":null,"abstract":"<p><p>To elucidate the mechanism of action of the <i>Astragalus membranaceus</i>-<i>Panax ginseng</i> herb pair in treating coronary heart disease (CHD) through network pharmacology combined with molecular docking and experimental validation. Active ingredients and target proteins were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. CHD-related targets were obtained from GeneCards and DrugBank. Overlapping targets were identified with a Venn diagram, and a protein-protein interaction network was built in STRING. Core targets were screened via topological analysis in Cytoscape 3.9.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed in Metascape. AutoDock Vina was used for molecular docking. <i>In vitro</i>, tumor necrosis factor (TNF)-α levels in HL-1 cells subjected to oxygen-glucose deprivation (OGD) were measured by ELISA, and the effect of mangiferin pretreatment on cell viability was assessed with a CCK-8 assay. Forty-one active ingredients and 207 putative targets were identified for the herbal pair, and 1843 CHD-related targets were collected; 67 overlapping therapeutic targets were obtained. Topological analysis yielded 27 core targets. GO terms were enriched in responses to lipopolysaccharide, toxic substances, and organic cyclic compounds; molecular functions included cytokine-receptor binding and transcription-factor binding; and cellular components were mainly membrane rafts and extracellular matrix. KEGG analysis highlighted the TNF, fluid-shear-stress, and NF-κB signaling pathways. Docking showed strong binding between key components and targets. <i>In vitro</i> experiments demonstrated that formononetin pretreatment significantly reduced OGD-induced TNF-α levels and improved HL-1 cell viability. The <i>A. membranaceus</i>-<i>P. ginseng</i> combination herb pair exerts anti-CHD effects via multiple bioactive ingredients (<i>e.g.,</i> formononetin, quercetin, isorhamnetin, ginsenoside Rh2, kaempferol) by targeting TNF, AKT1, PTGS2, and JUN and modulating pathways including the TNF and NF-κB signaling pathways.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"264-272"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793517","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 Role of the Glymphatic System in Alzheimer's Disease: Mechanisms, Evidence, and Therapeutic Implications.","authors":"Yaran Li, Juan Li, Xinhong Liu, Tao Wang, Li Ma, Ruifang She, Yanyan Chang","doi":"10.1177/15491684261442832","DOIUrl":"10.1177/15491684261442832","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an aging-associated neurodegenerative disorder characterized by amyloid-β (Aβ) and tau accumulation and progressive cognitive decline. Increasing evidence implicates the glymphatic system, a brain-wide perivascular pathway involved in cerebrospinal fluid-interstitial fluid exchange and metabolic waste clearance, in the removal of Aβ, tau, and other solutes relevant to AD pathogenesis. Aging-related alterations in aquaporin-4 polarization, arterial pulsatility, sleep architecture, and cerebrovascular integrity may impair glymphatic transport and thereby promote protein retention and neurodegeneration. In this review, we summarize current knowledge of glymphatic anatomy and function and discuss its implications for AD, with particular emphasis on modifiable factors such as sleep, exercise, vascular health, and aging-associated decline. We further highlight emerging therapeutic and potential intervention strategies aimed at restoring glymphatic function, and critically evaluate current methods for assessing this system in humans together with the evidence obtained to date. Although human studies increasingly support the relevance of perivascular fluid transport to AD-related pathology and cognitive outcomes, mechanistic insights remain largely derived from animal models, and human assessment is still constrained by methodological and imaging limitations. Overall, the glymphatic system provides a useful framework for linking brain aging to impaired clearance in AD. Further refinement of human biomarkers and longitudinal translational studies will be essential for clarifying their clinical relevance and therapeutic potential.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"225-234"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694466","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":"Pharmacodynamic Effects of <i>Salvia miltiorrhiza</i>-<i>Dalbergia Odorifera</i> in the Treatment of Ischemic Stroke Based on the Mixture Design.","authors":"Ziheng Ding, Chengzhao Liu, Kedi Liu, Weihong Li, Qi Dai, Hong Yao, Hefei Wang, Xinyan Cao, Peifeng Wei, Miaomiao Xi","doi":"10.1177/15491684261442837","DOIUrl":"10.1177/15491684261442837","url":null,"abstract":"<p><p><i>Salvia miltiorrhiza</i> (SM)-<i>Dalbergia odorifera</i> (DO) is a commonly used circulating blood and transforming stasis drug pair for the treatment of cardiovascular and cerebrovascular diseases, but systematic studies on the optimal ratio for the treatment of cerebrovascular diseases have not been reported. In this study, we determined the optimal ratio of SM-DO for the treatment of ischemic stroke (IS) through the mixture design.Five different ratios of SM and DO were applied to middle cerebral artery occlusion (MCAO) mice using an enhanced simplex center-of-mass mixture design by Minitab 17 software. The experimental ratios of SM and DO as independent variables and dependent variables including modified neurological severity scores, corner test, sticker removal test, cylinder test, 2,3,5-triphenyltetrazolium chloride staining, lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) levels, and the optimal ratio of the two herbs was obtained by fitting regression equations through mixture design and multi-objective synchronization optimization. The therapeutic effects of the optimal ratio of SM-DO on MCAO mice were verified and evaluated by the indicators of neurological function, brain swelling, cerebral infarction volume, brain histopathological morphology, and the levels of LDH and NSE. The optimal ratio of SM:DO = 0.61:0.39 was obtained by multi-objective synchronization optimization. The results of pharmacodynamic validation showed that the optimal ratio of SM-DO significantly improved the neurological function scores of MCAO mice, the motor functions of the left forelimb, the sensory functions of the left paw, the motor functions of the right steering, the cerebral infarct volume, and the release of LDH and NSE and exerted the therapeutic effect on IS. The optimal ratio of SM (0.61) and DO (0.39) was found to be effective in the treatment of IS mice based on mixture design.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"246-263"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725181","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":"Polysaccharide-Rich Herbal Formula Attenuates Skin Aging and Oxidative Stress in VCD-Induced Menopause Models via Regulation of AQP-3, C1QBP, and K19.","authors":"Yingqi Yu, Ruxi Gao, Guoshun Shan, Yi Yu, Yong Zhou","doi":"10.1177/15491684261441249","DOIUrl":"10.1177/15491684261441249","url":null,"abstract":"<p><p>To investigate the protective effects of Nvshi Oral Liquid on skin aging and oxidative stress in 4-vinylcyclohexene diepoxide (VCD)-induced menopausal rats and Ultraviolet B (UVB)-irradiated HaCaT cells. VCD-induced menopausal rats and UVB-damaged HaCaT cells under low-estrogen conditions were established. Nvshi Oral Liquid was administered at low (2%), medium (6%), and high (10%) concentrations. Cell viability, Reactive Oxygen Species (ROS) levels, antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase), inflammatory cytokines [Interleukin-1 beta, Interleukin-6, Tumor Necrosis Factor-alpha (IL-1β, IL-6, TNF-α)], and the expression of aquaporin-3 (AQP-3), complement component 1q binding protein (C1QBP), and keratin 19 (K19) were assessed using Cell Counting Kit-8 (CCK-8) assay, fluorescence staining, enzyme-linked immunosorbent assay, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR), and Western blot. Nvshi Oral Liquid significantly improved HaCaT cell viability, reduced ROS levels, enhanced antioxidant enzyme activities (SOD increased by 1.8-fold, <i>p</i> < 0.01), and suppressed inflammatory cytokines. Both mRNA and protein expression levels of AQP-3, C1QBP, and K19 were consistently increased in rat skin tissues and HaCaT cells. Histological analysis further demonstrated improved skin structure. Nvshi Oral Liquid attenuates menopausal skin aging by enhancing antioxidant capacity and restoring skin barrier function, which is associated with regulation of AQP-3, C1QBP, and K19 expression. These findings suggest a potential natural intervention for menopausal skin health.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"235-245"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647621","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":"Evaluating the Therapeutic Potential of <i>Hyriopsis cumingii</i> Polysaccharide in Osteoarthritis: Insights from a Mouse Model.","authors":"Hai-Liang Sun, Nattaya Wichienwantana, Wei-Kiat Wong, Tie-Li Duan, Jian Pang, Wan-Zhong Shi, Ying Shi","doi":"10.1177/15491684251414069","DOIUrl":"10.1177/15491684251414069","url":null,"abstract":"<p><strong>Background: </strong><i>Hyriopsis cumingii</i> polysaccharide (HCP) has been demonstrated to exhibit various biological activities. Our current research aimed to evaluate the protective effect of HCP on the osteoarthritis (OA) model mice.</p><p><strong>Methods: </strong>The therapeutic effect of HCP on OA was investigated by injecting monosodium iodoacetate into a mouse model of knee OA. The analgesic effect was assessed through behavioral analysis. The levels of serum antioxidant substances, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), as well as the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in articular cartilage, were measured by using enzyme-linked immunosorbent assay. The tissue morphology of articular cartilage was examined using hematoxylin-eosin and safranin O-fast green staining. Microcomputed tomography scans were employed to analyze the microstructure. Additionally, immunohistochemistry was utilized to detect the expression of type II collagen (COL2), matrix metalloproteinase (MMP)13, MMP3, IL-6, nuclear factor-kappa B (NF-κB), and TNF-α proteins in the articular cartilage. Additionally, the impact of HCP on gut microbiota (GM) was assessed through high-throughput fecal 16S ribosomal RNA sequencing.</p><p><strong>Results: </strong>The HCP significantly improved the gait of the mice; increased the levels of serum SOD, GSH-Px, and CAT; and reduced TNF-α and IL-6 in cartilage tissue. The surface of the articular cartilage appeared flat. Subchondral bone destruction was inhibited, and the bone volume fraction was significantly increased. The expression of COL2 was elevated, whereas the expressions of MMP13, MMP3, NF-κB, IL-6, and TNF-α were significantly decreased. HCP can also regulate the diversity of GM, increase the abundance of Firmicutes of GM, and significantly reduce the abundance of Bacteroidetes and Proteobacteria. The gram-negative and pathogenic phenotypes were downregulated in the low-, medium-, and high-dose HCP groups.</p><p><strong>Conclusions: </strong>HCP increases the levels of the body's antioxidant factors, improves the morphology of cartilage tissue, and optimizes the microstructure of subchondral bone, thereby inhibiting the progression of OA. Therapeutic efficacy HCP may be associated with the regulation of GM.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":"29 4","pages":"153-165"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304477","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":"Betulinic Acid Attenuates Vascular Smooth Muscle Cell Senescence and Aortic Vascular Aging via PPAR-α/CPT1A-Mediated Fatty Acid Oxidation.","authors":"Tingting Lu, Linghuan Wang, Sijia Chen, Tianhu Wang, Naiyuan Sun, Cheng Qin, Jin Yan, Yan Ma, Huijia Yin, Xiaoying Shen, Feng Cao","doi":"10.1177/15491684261429991","DOIUrl":"10.1177/15491684261429991","url":null,"abstract":"<p><p>Vascular stiffness and aging are critical contributors to cardiovascular diseases. Whether betulinic acid (BA), a natural triterpenoid, alleviates vascular aging remains unclear. Mouse aortic smooth muscle cells (MASMCs) with oleic acid (OA)-induced lipotoxic senescence were treated with BA (30 μM). Transcriptomic analysis and functional assays were conducted. <i>In vivo</i>, ApoE^-/- mice fed a high-fat diet received oral BA (25 mg/kg/day) for 14 weeks. OA-induced lipotoxic senescence was associated with overactivation of peroxisome proliferator-activated receptor alpha (PPAR-α)/fatty acid oxidation (FAO) signaling, which was attenuated by BA intervention. Molecular docking suggested that BA binds to the Arg226 site of PPAR-α, which was further supported by surface plasmon resonance analysis. BA significantly reduced OA-induced expression of P16, P21, and P53 (<i>p</i> < 0.05), inhibited reactive oxygen species generation, and improved mitochondrial function, indicating pronounced antisenescence effects of BA. Moreover, PPAR-α overexpression reversed these protective effects. In ApoE^-/- mice, BA intervention reduced vascular pulse wave velocity (2.7 ± 0.32 <i>vs.</i> 3.3 ± 0.45 m/s, <i>p</i> < 0.05) and intima-media thickness (0.114 ± 0.012 <i>vs.</i> 0.137 ± 0.018 mm, <i>p</i> < 0.05). BA attenuates MASMC lipotoxic senescence and aortic metabolism-associated vascular aging by inhibiting PPAR-α/carnitine palmitoyl transferase 1A-mediated FAO, suggesting a potential metabolic-targeted strategy for preventing lipid-associated vascular aging.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"166-177"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461347","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}