{"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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","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}
Rejuvenation researchPub Date : 2025-02-01Epub Date: 2024-09-16DOI: 10.1089/rej.2024.0039
Shang-Mei Cao, Meng Luo, Bo-Lin Chen, Xiu-Hong Fu
{"title":"Related Factors with Vascular Dementia: A Two-Sample Mendelian Randomization Study.","authors":"Shang-Mei Cao, Meng Luo, Bo-Lin Chen, Xiu-Hong Fu","doi":"10.1089/rej.2024.0039","DOIUrl":"10.1089/rej.2024.0039","url":null,"abstract":"<p><p>Pathogenesis of vascular dementia (VD) is still unclear, there are currently no effective prevention and treatment methods. We applied Mendelian randomization (MR) using summary statistics from large-scale GWAS of metabolites and VD to reveal the causal effect of metabolites on the VD. One set of genetics instrument was used for analysis, derived from publicly available genetic summary data. Which was 32 single-nucleotide polymorphisms robustly associated with metabolites. Inverse-variance weighted, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier test were used for MR analyses. Strong evidence for a positive effect of metabolites, which means N6-threonylcarbamoyladenosine (t<sup>6</sup>A) on VD was found in inverse-variance weighted (odds ratios [OR]: 0.667, 95% confidence interval [CI]: 0.548-0.812, <i>p</i> < 0.001), MR-Egger (OR: 0.647, 95% CI: 0.458-0.913, <i>p</i> = 0.019), and weighted median (OR: 0.650, 95% CI: 0.466-0.908, <i>p</i> = 0.012). The MR analysis indicated that metabolites (t<sup>6</sup>A) may be causally associated with a positive effect on VD.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121475","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":"Parishin Alleviates Pulmonary Fibrosis by Reducing CD38 Levels in Naturally Aging Mice.","authors":"Xinxiu Zhao, Shixian Zhou, Zhaoying Sheng, Linlin Sun, Qin Zhang, Yuanqiang Lu","doi":"10.1089/rej.2024.0042","DOIUrl":"10.1089/rej.2024.0042","url":null,"abstract":"<p><p>Parishin, a natural compound, has demonstrated significant potential in mitigating age-related phenotypes and improving outcomes in age-associated diseases. Given that aging is a major risk factor for numerous chronic conditions, including pulmonary fibrosis, we investigated parishin's effects on cellular senescence and lung health. In our study, we treated mouse lung epithelial cells with parishin and observed a reduction in cellular senescence markers alongside an upregulation of sirtuin 1 (SIRT1). Building on these <i>in vitro</i> findings, we administered parishin to naturally aged mice. The treatment resulted in decreased pulmonary fibrosis and reduced DNA damage in lung tissue. Notably, we found that parishin treatment led to a reduction in Cluster of differentiation 38 (CD38) levels, concomitant with an increase in SIRT1 expression. These findings indicate that parishin may enhance lung function in aged mice, suggesting its potential as a therapeutic agent for treating age-related pulmonary disorders.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"25-32"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rejuvenation researchPub Date : 2025-02-01Epub Date: 2024-10-24DOI: 10.1089/rej.2024.0052
Yu-Mei Zhong, Kun Luo, Yan-Ding Guo, Xiu-Hua Gao, Hai-Yan Zhou
{"title":"Moxibustion Regulates the Expression of T Cells in Rheumatoid Arthritis Through Tim-3/Gal-9 Signaling Pathway.","authors":"Yu-Mei Zhong, Kun Luo, Yan-Ding Guo, Xiu-Hua Gao, Hai-Yan Zhou","doi":"10.1089/rej.2024.0052","DOIUrl":"10.1089/rej.2024.0052","url":null,"abstract":"<p><p>To observe the effects of moxibustion on T cells and T cell immunoglobulin and mucin-domain-containing molecule-3/galectin-9 (Tim-3/Gal-9) pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. Thirty Sprague Dawley rats were randomly divided into three groups, including a control group, an RA model group, and a moxibustion group. An RA model was created through the injection of Freund's complete adjuvant. In the moxibustion group, rats were treated with moxibustion at acupoints of \"Shenshu\" and \"Zusanli.\" A total of three courses of treatment were conducted. Then the thickness of foot pad was measured, joint pathological changes were observed by hematoxylin-eosin (HE) staining, the proportion of CD4<sup>+</sup>T and CD8<sup>+</sup>T in peripheral blood was detected by flow cytometry, the expression levels of Tim-3 and Gal-9 in synovium were detected by polymerase chain reaction (PCR), and the expressions of CD4<sup>+</sup>T and CD8<sup>+</sup>T in synovium were detected by immunofluorescence. HE staining showed that the synovial tissue of the control group was smooth and neatly arranged without inflammatory cell infiltration. In the model group, the joint space was narrowed, the synovial tissue had congestion and edema, and a large number of inflammatory cells infiltrated. Compared with the model group, in the moxibustion group, the joint space narrowed with synovium hyperemia and edema, and the level of inflammatory cell infiltration decreased. Flow cytometry showed that compared with the model group, CD4<sup>+</sup>T expression in the moxibustion group was downregulated, while CD8<sup>+</sup>T expression was upregulated. PCR results showed that compared with the model group, the expressions of Tim-3 and Gal-9 in the moxibustion group were upregulated. Immunofluorescence results showed that compared with the model group, CD4<sup>+</sup>T expression in the moxibustion group was decreased, while CD8<sup>+</sup>T expression was increased. The results demonstrate that moxibustion not only suppressed the expression of CD4<sup>+</sup>T but also promoted the expression of CD8<sup>+</sup>T. The anti-inflammatory effect of moxibustion may be related to the regulation of T cell expression through the Tim-3/Gal-9 signaling pathway.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"17-24"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yehjoo Sohn, Yewon Hwang, Kimin Kim, Sung Je Lee, Ju Hun Yeon
{"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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","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}
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
{"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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","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":"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":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","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}
Rejuvenation researchPub Date : 2024-12-01Epub Date: 2024-09-09DOI: 10.1089/rej.2024.0030
M Nagaraju, Pandarinath Savitikadi, Krishna Kalyan Kalahasti, Utkarsh R Addi, G Bhanuprakash Reddy, S Sreenivasa Reddy
{"title":"Functional Food Mixture Extricates D-Galactose-Induced Skeletal Muscle Impairment in Rats.","authors":"M Nagaraju, Pandarinath Savitikadi, Krishna Kalyan Kalahasti, Utkarsh R Addi, G Bhanuprakash Reddy, S Sreenivasa Reddy","doi":"10.1089/rej.2024.0030","DOIUrl":"10.1089/rej.2024.0030","url":null,"abstract":"<p><p>Aging-related muscle atrophy/sarcopenia is the most common type of muscle impairment that affects the quality of life. In the current study, we examined the effect of a functional food mixture of amla, turmeric, black pepper, cinnamon, and ginger on D-galactose-induced muscle alterations in rats. Wistar rats were randomly divided into three groups: Control (C), D-galactose (G), and D-galactose + functional food mixture intervention (G + I). Rats in group-G and -G + I were injected with D-galactose (300 mg/kg/day) for 90 days. After 3 months of the experimental period, the rats were sacrificed to collect gastrocnemius muscle. Group-G rats showed elevated levels of inflammatory cytokines (TNFα and NF-kB), atrogenes (atrogin-1 and MuRF1), decreased insulin/IGF1 signaling (decreased AKT phosphorylation), altered mitochondrial dynamics (increased fission and decreased fusion proteins), increased apoptotic mediators (Bax/Bcl-2, and caspase-3), and decreased muscle cell cross-sectional area when compared with group-C (<i>p</i> < 0.05). Interestingly, supplementation with the functional food mixture prevented galactose-induced alterations in the muscle. The observed anti-inflammatory, insulin-sensitizing, mitochondria-protective, and antiapoptotic effects of the functional food could be the underlying mechanisms in displaying positive effects against galactose-induced muscle atrophy and, hence, may be useful for the prevention of age-related muscle disorders.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"181-190"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006227","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}