Rejuvenation research最新文献

{"title":"Aging and Rejuvenation Are Systemic, and So Is the Bipartisan Interest in Meaningful Longevity Therapeutics.","authors":"Irina Conboy","doi":"10.1177/15491684251360989","DOIUrl":"10.1177/15491684251360989","url":null,"abstract":"","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"157"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644468","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 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":"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}

{"title":"Causal Associations with Arterial Stiffness and Sarcopenia: A Mendelian Randomization Analysis.","authors":"Hengjun Liu, Tianwei Meng, Rui Qie","doi":"10.1089/rej.2024.0070","DOIUrl":"10.1089/rej.2024.0070","url":null,"abstract":"<p><p>Observational studies and clinical trials indicate a link between arterial stiffness (AS) and sarcopenia (SAR), yet the causal relationship between these remains unclear. The study aims to investigate the causal connection from AS to SAR by Mendelian randomization (MR). We analyzed Genome-Wide Association Studies data for AS indicators: pulse wave arterial stiffness index (PWASI) and pulse wave peak-to-peak time (PPT), and SAR indicators: low hand grip strength (LHGS), usual walking pace (UWP), moderate-to-vigorous physical activity levels (MVPA), and walk or cycle unassisted for 10 minutes. The inverse variance-weighted, MR-Egger, weighted mode, and weighted median were applied to MR. There is a bidirectional causal relationship between the AS and SAR. The PWASI has a causation with UWP (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.94-0.99). The PPT has a causal association with MVPA (OR = 1.08, 95% CI = 1.002-1.144) and UWP (OR = 1.05, 95% CI = 1.017-1.096). The LHGS is causally associated with PPT (OR = 0.95, 95% CI = 0.91-0.98) and UWP has a causal association with PWASI (OR = 0.77, 95% CI = 0.65-0.90) and PPT (OR = 1.37, 95% CI = 1.17-1.60). The increased AS could reduce the motor ability slightly and the lower upper and lower limb strength could lead to the higher AS. This bidirectional causal relationship of the two may offer novel perspectives for advancing the understanding of the underlying mechanisms related to AS and muscle pathophysiology.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"83-91"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901555","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":"Luteolin Exhibits Anxiolytic and Antidepressant Potential in Parkinson's Disease Rat: Antioxidant and Anti-Inflammatory Effects.","authors":"Ruifang She, Zhaoting Zhang, Miaomiao Han, Dapeng Zhao, Xiangting Li, Jian Zhou, Yanyan Chang, Xinping Zhang, Xiaohong Li","doi":"10.1089/rej.2024.0045","DOIUrl":"10.1089/rej.2024.0045","url":null,"abstract":"<p><p>Parkinson's disease (PD) is accompanied by a complex array of nonmotor and motor manifestations. The exploration of anti-inflammatory and antioxidant active ingredient as potential therapeutic interventions in PD-associated mood alterations has gained significant attention. This study aimed to assess the antidepressant and anxiolytic properties of luteolin (LTN), a potent antioxidant and anti-inflammatory component, using a 6-hydroxydopamine (6-OHDA)-induced animal model of PD. Rats were administered LTN (10, 25, and 50 mg/kg, per oral) and fluoxetine (10 mg/kg/per oral) over a 28-day period. Behavioral tests were employed to estimate the depression- and anxiety-like behaviors. Rats treated with LTN exhibited significant improvement in 6-OHDA-induced mood alterations, as per behavioral tests. Additionally, LTN treatment led to increased hippocampal levels of catalase and superoxide dismutase, and a reduction in malondialdehyde. LTN downregulated the gene expression of nuclear factor kappa B (NF-κB)/nod-like receptor (NLR) pyrin domain-containing 3 (NLRP3) axis components, including NF-κB, NLRP3, ASC, and Caspase1 and reduced the protein level of pro-inflammatory cytokines, including interleukin (IL)-6, interleukin (IL)-1β, and tumor necrosis factor alpha (TNF-α), in addition to augmenting the protein levels of TNF-α, IL-1β, and IL-6. Furthermore, LTN exhibited an upregulatory effect on the anti-inflammatory cytokine IL-10 within the hippocampus of 6-OHDA-induced PD rats. Also, molecular docking showed higher affinity between LTN and NF-κB/NLRP3 axis components. These findings highlight the potential anxiolytic and antidepressant impacts of LTN through its antioxidant and anti-inflammatory mechanisms against 6-OHDA-induced alterations in a rat PD model.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"67-82"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901556","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":"Systems Pharmacology to Explore the Potential Mechanism of Ginseng Against Heart Failure.","authors":"Kai Gao, Dong Xu, Fei Mu, Meina Zhao, Wei Zhang, Xingru Tao, Chao Guo, Jingwen Wang","doi":"10.1089/rej.2024.0051","DOIUrl":"10.1089/rej.2024.0051","url":null,"abstract":"<p><p>The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while <i>FN1</i> and <i>PRKAA2</i> were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets. <i>In vivo</i> experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1β, IL-6, and TNF-α. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NFκB, TGF-β, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"54-66"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592351","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}