Rejuvenation research最新文献

{"title":"The Epigenetic Landscape: From Molecular Mechanisms to Biological Aging.","authors":"Rachel Evangelina, Subhashree Ganesan, Melvin George","doi":"10.1089/rej.2024.0102","DOIUrl":"10.1089/rej.2024.0102","url":null,"abstract":"<p><p>Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the deoxyribonucleic acid (DNA) sequence, plays a pivotal role in cellular function, development, and aging. This review explores key epigenetic mechanisms, including DNA methylation (DNAm), histone modifications, chromatin remodeling, RNA-based regulation, and long-distance chromosomal interactions. These modifications contribute to cellular differentiation and function, mediating the dynamic interplay between the genome and environmental factors. Epigenetic clocks, biomarkers based on DNAm patterns, have emerged as powerful tools to measure biological age and predict health span. This article highlights the evolution of epigenetic clocks, from first-generation models such as Horvath's multi-tissue clock to advanced second- and third-generation clocks such as DNAGrimAge and DunedinPACE, which incorporate biological parameters and clinical biomarkers for precise age estimation. Moreover, the role of epigenetics in aging and age-related diseases is discussed, emphasizing its impact on genomic stability, transcriptional regulation, and cellular senescence. Epigenetic dysregulation is implicated in cancer, genetic disorders, and neurodegenerative diseases, making it a promising target for therapeutic interventions. The reversibility of epigenetic modifications offers hope for mitigating age acceleration and enhancing health span through lifestyle changes and pharmacological approaches.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"93-112"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652947","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":"Causal Association of Sleep Traits with All-Cause and Cause-Specific Mortality: A Prospective Cohort and Mendelian Randomization Study.","authors":"Jinjin Zhang, Hao Yu, Lirui Jiao, Di Wang, Yeqing Gu, Ge Meng, Hongmei Wu, Xuehui Wu, Dandan Zhu, Yinxiao Chen, Dongli Wang, Yaxiao Wang, Hao Geng, Tao Huang, Kaijun Niu","doi":"10.1089/rej.2024.0058","DOIUrl":"10.1089/rej.2024.0058","url":null,"abstract":"<p><p>The study aimed to explore the association between different sleep traits and all-cause mortality as well as to validate causality in the association through mendelian randomization (MR). We analyzed 451,420 European ancestry participants from the UK Biobank. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the association between sleep traits and all-cause mortality. In MR analysis, the inverse variance weighting (IVW) method was applied as the primary analysis to investigate the causal association between sleep traits and mortality. During a median follow-up period of 12.68 years, 34,397 individuals died. Observational analyses showed the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (CIs) for short sleep, long sleep, early chronotype, daytime sleepiness, daytime napping, and insomnia with mortality, 1.246 (1.195, 1.298), 1.735 (1.643, 1.831), 0.931 (0.909, 0.953), 1.276 (1.212, 1.344), 1.299 (1.254, 1.346), and 1.117 (1.091, 1.142) (All <i>p</i> < 0.0001). Based on UK Biobank, MR analysis indicated the association between daytime napping and an increased risk of all-cause mortality (odd ratio [OR]: 1.219, 95% CI: 1.071-1.387, <i>p</i> = 0.003), which may be largely attributable to cancer disease mortality (OR: 1.188, 95% CI: 1.009-1.399, <i>p</i> = 0.039). We found no causal association between sleep duration, short sleep, long sleep, chronotype, daytime sleepiness, insomnia, and mortality risk. The causal associations between sleep traits and all-cause mortality risk were directionally replicated in FinnGen. Our findings suggest a potential causal association between daytime napping and increased risk of all-cause mortality in middle-aged and older persons. The finding could have important implications for evaluating daytime napping habits to decrease the risk of mortality.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"136-145"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070579","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":"Relationship of α-Klotho with Frailty Index and Sarcopenia: A Bidirectional Mendelian Randomization Study.","authors":"Yue Zhu, Guo-Jun Hong, Yong Hu, Rui Wu","doi":"10.1089/rej.2024.0057","DOIUrl":"10.1089/rej.2024.0057","url":null,"abstract":"<p><p>Previous studies have established associations between α-Klotho and frailty or sarcopenia; however, the causal nature of these relationships remains unclear. This study investigates the causal effects of α-Klotho on frailty and sarcopenia-related traits using Mendelian randomization (MR). Genetic instruments for circulating α-Klotho concentrations, frailty index (FI), low grip strength (LGS), appendicular lean mass (ALM), and walking pace were developed based on data from large genome-wide association studies. Two-sample MR analyses were performed, supplemented by sensitivity analyses to ensure the robustness of the findings. Reverse MR analyses were also conducted to explore potential reverse causation. The findings demonstrated an inverse causal relationship of circulating α-Klotho levels with FI (<i>β</i> = -0.020, 95% confidence interval [95% CI] = -0.036 to -0.004; <i>p</i> = 0.017) and LGS (<i>β</i> = -0.033, 95% CI = -0.061 to -0.004; <i>p</i> = 0.023). However, no causal relationship was observed between circulating α-Klotho levels and ALM or walking pace. Additionally, no evidence of reverse causation was identified between FI or sarcopenia-related traits and circulating α-Klotho levels. In conclusion, this MR analysis establishes an inverse causal relationship of circulating α-Klotho levels with both FI and LGS.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"146-155"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082720","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":"Comparison of Antioxidant Activities of <i>Dendropanax morbifera Léveille</i> Extracts According to Harvest Area.","authors":"Yehjoo Sohn, Yewon Hwang, Kimin Kim, Sung Je Lee, Ju Hun Yeon","doi":"10.1089/rej.2024.0043","DOIUrl":"10.1089/rej.2024.0043","url":null,"abstract":"<p><p><i>Dendropanax morbifera Léveille</i> is a medicinal plant native to East Asia with its diverse therapeutic potentials. In particular, the antioxidant effect of this plant is well known, but there has been little research on the antioxidant effect according to different habitats or ages. In this study, we evaluated the proximate composition, mineral, saponin, rutin, total phenolic and flavonoid contents, and antioxidant activities of leaf extracts of <i>D. morbifera</i> plants cultivated from two different regions (New Zealand and Jeju Island, Korea) and of the same age (2-year-old plants). The assessment of proximate composition and total phenolic and flavonoid contents revealed significant variations in these parameters dependent on the cultivation region and age. The highest total phenol and total flavonoid contents were observed in <i>D. morbifera</i> from Jeju Island. In addition, the antioxidant activities of leaf extracts of <i>D. morbifera</i> from different cultivation regions and ages were assessed in terms of 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)free radical scavenging, total antioxidant capacity, and superoxide dismutase activity. The extract of <i>D. morbifera</i> from Jeju Island showed the highest antioxidant activity among the samples tested. These findings clearly indicate that both the cultivation region and plant age affect the phytochemical content and antioxidant activity of <i>D. morbifera</i>. Therefore, extracts of <i>D. morbifera</i> obtained from optimal harvest regions and ages could serve as promising natural antioxidant candidates with potential health benefits.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"125-135"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070585","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":"Tripartite Motif-Containing Protein 65 Promotes Proliferation and Inhibits Ferroptosis in Prostate Cancer via Enhancing NKD Inhibitor of WNT Signaling Pathway 2 Ubiquitination.","authors":"Chengcai Wang, Huamao Jiang","doi":"10.1089/rej.2024.0061","DOIUrl":"10.1089/rej.2024.0061","url":null,"abstract":"<p><p>As a typical E3 ligase, tripartite motif-containing 65 (TRIM65), is implicated in the modulation of biological processes, such as metastasis, proliferation, and apoptosis. However, the function of TRIM65 in prostate cancer (PCa) and its potential mechanism have not yet been excavated. In this work, we affirmed Tripartite motif-containing protein 65 (TRIM65) as a new oncogene in PCa, which accelerated PCa cell proliferation and impeded cell ferroptosis. <i>In vivo</i>, depletion of TRIM65 inhibited PCa tumorigenesis and metastasis. Mechanically, our findings uncovered that TRIM65 enhances NKD inhibitor of WNT signaling pathway 2 (NKD2) degradation via the ubiquitin-proteasome signaling. TRIM65 facilitated proliferation and restricted ferroptosis via downregulating NKD2 levels. Moreover, TRIM65 activated the wingless-integrated/β-catenin pathway in PCa cells via inhibiting NKD2. Taken together, these data uncovered that TRIM65 controls PCa proliferation, and ferroptosis and regulates the Wnt/β-catenin signaling via directly targeting NKD2 for ubiquitination degradation. Our study provides insights into the multifaceted regulatory role of TRIM65 in the development of PCa, laying the foundation for exploring new therapeutic approaches.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"113-124"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883766","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":"Umbilical Cord Blood Plasma Enhances Cellular Repair and Senescence Suppression in Human Dermal Fibroblasts Under Oxidative Stress.","authors":"Miso Jeong, Hyangju Lee, Tae-Hyun Ko, Soo Jin Choi, Wonil Oh, Sangwoo Kim","doi":"10.1089/rej.2024.0085","DOIUrl":"https://doi.org/10.1089/rej.2024.0085","url":null,"abstract":"<p><p>Aging is associated with a gradual decline in cellular function, largely driven by oxidative stress, which leads to cellular senescence. These processes contribute to tissue degeneration and age-related dysfunction. Human dermal fibroblasts (HDFs), critical for maintaining skin structure, are highly vulnerable to oxidative damage, making them key contributors to skin aging. Umbilical cord blood plasma (UCBP), rich in growth factors and regenerative molecules, has shown potential in preventing cellular senescence and addressing key mechanisms of tissue aging. Based on findings from heterochronic parabiosis experiments that demonstrated the rejuvenating effect of young blood, we investigated the effects of UCBP on hydrogen peroxide (H₂O₂) induced oxidative stress in HDFs and compared its efficacy with adult blood plasma (ABP). Our results indicate that although both UCBP and ABP reduce reactive oxygen species (ROS), UCBP is more effective in suppressing cellular senescence and maintaining fibroblast proliferation. These findings suggest that UCBP's protective effects extend beyond ROS reduction, potentially by modulating the senescence-associated secretory phenotype and the enhancement of tissue repair mechanisms.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015543","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":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","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":"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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","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":"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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","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":"Continuing the Legacy: Understanding and Reducing Tissue Aging to Prevent Many Currently Incurable Diseases.","authors":"Irina Conboy","doi":"10.1089/rej.2025.0012","DOIUrl":"10.1089/rej.2025.0012","url":null,"abstract":"","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"35-36"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598465","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}