Rejuvenation research最新文献

Aging is characterized by a progressive decline in physiological integrity, often accompanied by chronic inflammation and immune dysregulation. Immunoglobulin G (IgG), a key effector of humoral immunity, undergoes substantial structural and functional remodeling with age, particularly through changes in its glycosylation profile. These modifications shift IgG toward a proinflammatory state, linking it to inflammaging and multiple age-related diseases. This review synthesizes recent advances in understanding how IgG contributes to immune aging, with a specific focus on its glycosylation-dependent functions, tissue accumulation, and bidirectional crosstalk with the gut microbiota. We also highlight the potential of IgG as a biomarker and therapeutic target in aging-related interventions. We discuss the dual functional architecture of IgG and how age-related glycan shifts-namely, increased agalactosylation, afucosylation, and bisecting N-acetylglucosamine (GlcNAc)-enhance binding to activating Fcγ receptors, amplifying proinflammatory signaling. Experimental studies demonstrate that IgG accumulation in adipose tissue contributes to metabolic dysfunction via Neonatal Fc Receptor (FcRn)-dependent pathways. Additionally, sex hormones modulate IgG glycosylation patterns, partially explaining sex-specific differences in immune aging. The concept of "glycan clocks" has emerged as a tool to assess biological age and intervention responsiveness. Moreover, the gut microbiota plays a critical role in shaping the IgG repertoire, and aging disrupts this IgG-microbiota axis, resulting in altered mucosal immunity and systemic inflammation. Interventions targeting this axis-including microbiota modulation and glycoengineering-offer promising translational avenues for immune rejuvenation. Finally, we review emerging therapeutic strategies that leverage the gut-immune interface to mitigate aging-associated cardiovascular and metabolic diseases. IgG is not merely a biomarker but an active participant in the aging process, functioning at the intersection of immune regulation, microbial symbiosis, and systemic inflammation. Its age-associated transformation reflects broader changes in host immunity and highlights new opportunities for precision interventions in immunosenescence.

Background: Facet joint osteoarthritis (FJOA) is a serious facet joint cartilage degeneration disorder, which is an important cause of low back pain and disability. Bushenhuoxue formula (BSHXF), a traditional Chinese herbal compound, has been demonstrated to exhibit the ability to improve osteoarthritis. This study aimed to uncover the therapeutic effect and potential mechanism of BSHXF in FJOA. Methods: FJOA rats were treated with BSHXF. Histological staining, immunohistochemistry, TUNEL staining, and flow cytometry were performed for detecting pathological damage, molecule expressions in articular cartilage, chondrocyte apoptosis, and pyroptosis, respectively. Interleukin (IL)-18 and IL-1β levels were quantified with enzyme-linked immunosorbent assay. RT-qPCR and Western blot were carried out for evaluating mRNA and protein expressions. Immunofluorescence and coimmunoprecipitation were used to study the colocalization and interaction between Caspase-11 and Nod-like receptor protein-3 (NLRP3) in chondrocytes. Results: In FJOA rats, BSHXF attenuated articular cartilage pathological damage. Specifically, BSHXF inhibited matrix degradation, as indicated by increasing collagen II and decreasing matrix metalloproteinase 13. BSHXF inhibited articular chondrocyte apoptosis and promoted chondrocyte proliferation. BSHXF decreased Caspase-1 and NLRP3, reduced the rate of Caspase-1/propidium iodide-stained chondrocytes, and inhibited inflammatory cytokines, indicating the attenuated articular chondrocyte pyroptosis. BSHXF downregulated Caspase-11, loosened the interaction between NLRP3 and Caspase-11, as well as upregulated transactive response DNA-binding protein 43 (TDP-43) in FJOA rats. Additionally, in H₂O₂-exposed chondrocytes, TDP-43 overexpression decreased TLR4, p-IκBα, NF-κB P65, and Caspase-11 and declined the co-localization of Caspase-11 and NLRP3. Importantly, TDP-43 knockdown reversed BSHXF-mediated protective effects in FJOA rats. Conclusion: BSHXF inhibited chondrocyte pyroptosis by increasing TDP-43 to protect against FJOA via loosening the interaction of Caspase-11 and NLRP3, which may provide a fundamental basis for treating FJOA cartilage damage. [Figure: see text].

Successful aging is essential for health, particularly as the global population of older adults rises. It assesses whether older adults maintain a healthy lifestyle and enjoy quality in their later years. This study explores the relationship between successful aging and mortality, focusing on how its components relate to mortality across different genders. We conducted a longitudinal analysis of 9633 older adults (aged 65+) from the Chinese Longitudinal Healthy Longevity Survey (2011-2018). This study used two definitions of successful aging: SA I includes five dimensions (the absence of major diseases, no subthreshold depression, freedom from disability, high cognitive function, and active social participation); SA II consists of four dimensions and excludes the absence of major diseases. Both genders exhibited lower mortality rates among those achieving successful aging (males: hazard ratio [HR] = 0.62 for SA I, HR = 0.65 for SA II; females: HR = 0.57 for SA I, HR = 0.58 for SA II). All successful aging dimensions correlated with reduced death risk, except for subthreshold depression in females. In males, significant reductions in mortality were linked to freedom from disability (HR = 0.49) and active social participation (HR = 0.60). In females, these were notable for freedom from disability (HR = 0.46) and high cognitive function (HR = 0.47). SA I, which includes the absence of major diseases, is more relevant for Chinese younger old. The influence of successful aging components on mortality risk varies by gender, emphasizing the importance of addressing functional daily living challenges to enhance the health of older adults in China.

Oxidative stress (OS) causes biochemical and morphological alterations in erythrocytes. The primary factors contributing to OS are aging and storage. Antioxidants significantly alleviate OS. Therefore, this study aimed to investigate the response of young and old erythrocytes to vitamin C and vitamin E during storage. Erythrocytes were separated into young and old by the Percoll method. Each erythrocyte subpopulation was categorized into the i) Control (additive solution-7 [AS-7]) and ii) vitamin C and vitamin E in AS-7 (VC+VE) groups and stored for 21 days at 4°C. OS, antioxidant, and aging markers were analyzed on days 1, 14, and 21. The activity of antioxidant enzymes was similar throughout storage in young cells. However, superoxide dismutase activity elevated in old cells (Control and VC+VE) on days 1 and 21. Catalase (CAT) activity increased on days 14 and 21, whereas glutathione peroxidase (GPX) increased on days 1 and 14 in old Controls. However, in old VC+VE, CAT increased on day 21 and GPX increased on day 1. Advanced oxidation protein products, superoxides, glutathione, and uric acid increased in old cells throughout storage. Malondialdehyde decreased in old VC+VE compared with old Control on days 14 and 21. Sialic acids and glutamate oxaloacetate transaminase activity were higher in young cells compared to old cells. Young cells exhibited lower oxidative changes throughout storage. Vitamin C and vitamin E were effective in maintaining the redox balance in old cells. These findings emphasize the need for specific approaches for different subpopulations during erythrocyte banking.

Previous studies on sarcopenia and COVID-19 have primarily focused on pathophysiological mechanisms, leaving the effects of social isolation policies largely unexplored. Taiwan offers a unique environment to investigate this issue. This study investigates the association between COVID-19-related isolation and sarcopenia in older adults in Taiwan. Participants aged 65 and older were enrolled from annual geriatric health check-ups conducted between 2018 and 2023. The years from 2018 to 2020 were designated as the pre-COVID-19 period, while 2022-2023 was considered the post-COVID-19 era. Demographic data and health conditions were collected. The assessments encompassed body composition, muscle strength, and physical performance. The prevalence and trends of sarcopenia were analyzed. The prevalence of low muscle strength declined in 2021 but subsequently increased from 2022 to 2023 (p_quadratic = 0.018). In 2023, compared with 2018-2020, the odds ratio for sarcopenia and severe sarcopenia was 1.3 (95% confidence interval [CI] 1.01-1.67), and the odds ratio for low physical performance was 1.73 (95% CI 1.39-2.15). This is the first report describing the association between COVID-19 pandemic-related policies and the prevalence of sarcopenia, revealing a significant increase in sarcopenia prevalence following the pandemic. Our results emphasize the necessity of tailored strategies to support older adults during and after health crises.

Elevated levels of Bicaudal-D Family Like Cargo Adaptor 1 (BICDL1) are associated with poor prognosis in various cancers. However, the role of BICDL1 in breast cancer (BC) has not been reported. We analyzed BICDL1 expression in BC using bioinformatics and molecular experiments. Gene Set Enrichment Analysis was conducted to identify significantly enriched signaling pathways related to BICDL1. The effects of BICDL1 on BC cell proliferation, migration, invasion, and expression of epithelial-mesenchymal transition (EMT)-related proteins were assessed using colony formation assays, Transwell assays, and Western blot. The influence of BICDL1 on pyroptosis in BC cells was determined by measuring the expression of key pyroptosis proteins (NLRP3, GSDMD-N, procaspase-1, cleaved caspase-1, ASC), lactate dehydrogenase release, and cytokines (IL-1β and IL-18). We also investigated whether BICDL1 promotes BC proliferation and metastasis by regulating pyroptosis using Nigericin, an agent that induces NLRP3 inflammasome activation. The results showed that BICDL1 was significantly overexpressed in BC tissues and cells. Knockdown of BICDL1 inhibited BC cell proliferation, migration, invasion, and the EMT process, while overexpression of BICDL1 had the opposite effects. BICDL1 was enriched in the pyroptosis pathway; overexpression of BICDL1 suppressed pyroptosis, thus promoting BC cell proliferation, inhibition, and migration. Notably, the addition of Nigericin reversed the effects of BICDL1 overexpression on BC cells. These results suggested that BICDL1 promoted BC cell proliferation, inhibition, and migration by hindering pyroptosis. These findings indicate that BICDL1 is a potential biomarker for BC treatment.

This study investigates the correlation between polypharmacy and gut microbiota compositional changes in older people who were treated with multidrug therapy, aiming to provide insights into the complex interplay between medication use, gut microbiota, and aging. High-throughput sequencing of the 16S rRNA gene was employed to analyze microbial diversity in older patients with multiple chronic diseases and polypharmacy, and the results were compared with a control group of older people without multiple chronic diseases and not undergoing polypharmacy. The study revealed distinct differences in gut microbiota composition between the two groups, with lower alpha-diversity observed in multidrug therapy group. Furthermore, the analysis identified several significant differences in microbiome composition at the genus and family levels between the multidrug therapy and the control group. The findings underscore the importance of understanding the impact of polypharmacy on the gut microbiota and its relationship to overall health in older people. Additionally, the study provides insights into the potential effects of specific medications, such as antihypertensive drugs, proton pump inhibitors, and antibiotics, on the gut microbiota, highlighting the need for continued research in this critical area to optimize therapeutic strategies for the older population.

Emerging evidence suggests that bioactive peptides from various foods have therapeutic potentials in improving cognitive function in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We aimed to explore the characteristics of these peptides and their mechanisms on AD/MCI using a network pharmacology approach. We compiled a dataset of cognition-enhancing peptides from literatures and identified shared targets between these peptides and AD/MCI using Swiss Target Predication, PharmMapper, OMIM, GeneCards, TTD, and Drugbank databases. We then performed functional enrichment analysis and constructed a gene-gene interaction network to identify key hub targets. Additionally, we investigated the transcription factors (TFs) and microRNAs (miRNAs) regulating these hub genes. Molecular docking and dynamic simulations were performed using AutoDock Vina and GROMACS. We identified 59 cognition-enhancing oligopeptides, typically short and rich in arginine. These peptides were predicted to interact with 222 potential targets relevant to AD/MCI, with functional pathways mainly involving neuroactive ligand-receptor interactions and inflammation. We identified 15 hub targets, regulated by 144 TFs and 95 miRNAs. Notably, peptides containing the "Trp-Tyr" sequence demonstrated strong binding affinities to many hub targets, especially matrix metalloproteinase-9. The findings provided valuable insights into the molecular mechanisms through which bioactive peptides may act against AD/MCI and highlight the potential of network pharmacology for future exploration of bioactive peptides from natural foods.

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.

Background: 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. Objective: This study aimed to determine the causal relationship between GM and KOA and to quantify the potential mediating role of BMs. Methods: 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. Results: 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 N-formylanthranilic acid (6.55%). Sensitivity and reverse causality analyses further supported the robustness of these findings. Conclusion: 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.