Biogerontology最新文献

Background: Epigenetic age acceleration (EAA) is a biomarker of biological aging associated with multiple diseases. Plasma metabolites are potential targets for disease prevention. Therefore, our study aims to investigate the association between plasma metabolites and EAA.

Methods: Statistics of plasma metabolites and EAA were obtained from the GWAS database. After rigorously screening the instrumental variables, we applied five Mendelian randomization methods to evaluate the relationship between each metabolite and the EAA. The robustness of the results was verified by a series of sensitivity analyses, and metabolic pathway enrichment analysis was performed for significantly associated metabolites.

Results: Our analysis identified 149 plasma metabolites associated with EAA (p < 0.05), including 46 metabolites associated with IEAA, 47 with HannumAge, 38 with GrimAge, and 41 with PhenoAge. Among these, palmitoylcarnitine levels remained correlated with EAA after multiple testing correction (P_FDR < 0.05). In the enrichment analysis, 13 metabolic pathways were associated with EAA. Among them, "cysteine and methionine metabolism" was identified as the most significantly enriched pathway (P_FDR < 0.1), and 3 metabolites in this pathway were correlated with EAA.

Conclusion: These results demonstrated that plasma metabolomics, particularly amino acid and lipid metabolism, were associated with EAA and aging. The "cysteine and methionine metabolism" pathway emerged as a potential mechanism of aging, and may underpin metabolic alterations during the aging process, and its metabolites, such as methionine, 5-methylthioadenosine, and α-ketobutyrate, may serve as intervention targets.

Ziziphus jujuba Mill. (ZJ) is a traditional medicinal plant known for its antioxidant, anti-inflammatory, and neuroprotective properties, yet its role in learning and cognitive regulation remains insufficiently explored. Huang Jing (Polygonatum sibiricum), a Qi- and Yin-tonifying herb in Traditional Chinese Medicine, has historically been used to combat fatigue, support brain function, delay aging, and regulate metabolic balance. In this study, we evaluated the neuroprotective and antioxidant effects of the combined formulation Hong Huang Tang in Caenorhabditis elegans under simulated microgravity conditions. Behavioral assays, including lifespan, chemotaxis-based learning, pharyngeal pumping, head thrashing, and body bending, were performed to assess cognitive and neuromuscular function. Mitochondrial health and oxidative stress markers were quantified, alongside expression of antioxidant defense genes. DAF-16::GFP localization and sod-3 expression were analyzed to determine involvement of insulin/IGF-1 signaling. Additionally, neuroprotection against 6-hydroxydopamine-induced dopaminergic degeneration was assessed. Simulated microgravity triggered oxidative stress, mitochondrial dysfunction, reduced lifespan, impaired learning, and neuromuscular decline. Treatment with 2 mg/mL Hong Huang Tang significantly reversed these effects, restoring mitochondrial function, enhancing antioxidant capacity, and alleviating neurodegeneration. These findings support Hong Huang Tang as a promising therapeutic candidate for oxidative stress-related cognitive decline and neurodegenerative disorders.

As a target organ in direct contact with external air, lung tissue is more susceptible to aging, and lung aging is closely related to the development of chronic lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis. Evolutionarily speaking, the Wnt signaling pathway is highly conserved and plays an important role in embryonic development, tissue homeostasis, as well as cell proliferation, differentiation, apoptosis, and migration of a variety of cells. Alterations in Wnt signaling pathway activity can accelerate the pathological process of chronic lung diseases. In recent years, a large number of studies have focused on the regulatory role of the Wnt signaling pathway in the lung aging process and aging-related chronic lung diseases. Therefore, this paper systematically reviews the relationship between the Wnt signaling pathway and lung aging and its role in aging-related chronic lung diseases.

This paper focuses specifically on the education and upskilling of medical doctors, proposing how longevity-related competencies can be incorporated first through continuing medical education (CME) pathways and, eventually, into formal medical curricula. As longevity medicine evolves from research into clinical practice, education has emerged as its defining challenge. While the science of ageing advances rapidly, most physicians remain unprepared to translate biological, technological, and preventive insights into responsible medical care. Emerging foundational fields such as biogerontology, which investigates the biological mechanisms of ageing across organisms, and its clinically oriented derivative geroscience, have created new expectations for translational capacity in healthcare. This paper extends previous conceptual work by outlining potential educational domains, proposing a structured education, and outlining a pedagogical and accreditation model for incorporating longevity-related competencies into medical training pathways. The framework integrates geroscience, digital diagnostics, and healthspan-oriented care within established medical education and quality assurance standards. By exploring potential pathways from postgraduate to continuing education, longevity medicine may contribute to more coherent and evidence-aligned practice. Education may represent one enabling factor in efforts to shift, where feasible, from predominantly reactive care toward more proactive approaches to health maintenance.

This study aims to analyze the global research landscape and identify emerging trends in research hotspots, key technologies, and clinical applications in proteomics research in aging from 1998 to June 20, 2025. Publications related to aging and proteomics from 1998 to June 20, 2025 were retrieved from the Web of Science Core Collection. A bibliometric analysis was conducted using VOSviewer, CiteSpace, and R 4.3.3 to evaluate publication trends, research collaborations, and emerging topics. A total of 3,638 studies were included in the analysis. The USA, China, and Germany led in publication volume with 983, 829, and 227 articles respectively. Harvard University was the most prolific institution with 306 publications, followed by University of California System and Chinese Academy of Sciences. Key research was published in high-impact journals such as Journal of Proteome Research, Aging Cell, and Proteomics. Luigi Ferrucci, and D. Allan Butterfield were the most influential authors. Cluster analysis identified five research hotspots: protein expression and cellular senescence mechanisms, age-related diseases and neurodegeneration, cellular processes and molecular mechanisms, stress response and longevity mechanisms, and advanced proteomics technologies and biomarker discovery. Burst keyword analysis revealed recent research hotspots including health, dementia, extracellular vesicles and receptor. This study demonstrates that aging proteomics research has matured into distinct yet interconnected domains spanning basic molecular mechanisms, clinical disease applications, and technological innovations, reflecting the field's evolution toward translational and precision medicine approaches for age-related conditions. Future research directions may focus on clinical translation of aging biomarkers and development of precision medicine approaches for age-related diseases.

Population ageing is a global phenomenon with significant implications for public health. Research has highlighted a relationship between gut microbiota, inflammatory cytokines, and ageing, yet the underlying causal mechanisms remain elusive. This study uses Mendelian randomization (MR) analysis to investigate causal relationships between gut microbiota, inflammatory cytokines, and ageing phenotypes. We leveraged the summary statistics of gut microbiota (n = 5959), circulating inflammatory cytokines (n = 8293), and three ageing phenotypes including telomere length (n = 472,174), facial ageing (n = 423,999), and frailty index (n = 175,226). We performed bidirectional MR analyses to explore the causal effects of gut microbiota and inflammatory cytokines on ageing, and mediation analyses to discover potential mediating gut microbiota and inflammatory cytokines. Our findings suggest that there are causal interactions between gut microbiota, inflammatory cytokines, and ageing. Notably, the abundance of GCA-900066575 sp900066385 appears to mediate the M-CSF pathway to facial ageing. The current MR study provides evidence supporting causal relationships between inflammatory cytokines and ageing and potential mediating gut microbiota, which are critical to advancing our understanding of the ageing process and developing effective interventions.

Liver-expressed antimicrobial peptide-2 (LEAP-2), the endogenous antagonist of the ghrelin receptor (GHSR1a), counterbalances ghrelin in an energy- and inflammation-dependent manner. Aging is accompanied by endocrine and immunometabolic shifts that may influence this axis. We investigated whether a short course of broad-spectrum antibiotics (vancomycin-metronidazole-neomycin-ampicillin; VMNA) alters LEAP-2 and ghrelin levels in the liver and epididymal white adipose tissue (WAT) of aged male rats, and whether these changes coincide with modifications in IL-10, TNF-α, and IL-1β. Antibiotic treatment lowered LEAP-2 in both liver and WAT. Ghrelin decreased in both tissues, but the reduction reached significance only in WAT, whereas the hepatic decrease was nonsignificant. Consequently, the LEAP-2/ghrelin ratio declined in the liver and showed a nonsignificant upward trend in WAT. Inflammatory profiling revealed that IL-10 decreased in both tissues, whereas TNF-α and IL-1β remained unchanged. These findings demonstrate that even a one-week antibiotic regimen induces tissue-specific alterations in the LEAP-2/ghrelin axis-characterized by reduced hepatic LEAP-2 signaling, suppressed adipose ghrelin, and diminished anti-inflammatory tone. Overall, the data suggest that aged male rats exhibit heightened vulnerability to antibiotic-induced perturbations in LEAP-2/ghrelin regulation, underscoring the interplay between microbiota-related influences, inflammaging, and age-associated metabolic imbalance.

Postoperative cognitive dysfunction (POCD) is a prevalent neurocognitive disorder in elderly patients following surgery and anesthesia. However, the underlying mechanisms remain poorly understood, and treatment options are limited. This study applied a multi-omics strategy, combining cognitive-behavioral assessments with proteomic and metabolomic profiling, to uncover the molecular basis of POCD in an aged mouse model. Behavioral assessments, including the Morris Water Maze (MWM), Open Field Test (OFT), and Novel Object Recognition (NOR), revealed significant cognitive deficits in POCD mice. Proteomic analysis identified 103 differentially expressed proteins (DEPs), with 34 upregulated and 69 downregulated, alongside significant correlations among 16 proteins. Enrichment analysis indicated disturbances in mitochondrial energy metabolism and epigenetic regulation, linked to neurodegenerative pathways. Metabolomic profiling detected 99 metabolites, with 66 upregulated and 33 downregulated, confirming their differential expression between groups. Correlation analysis between DEPs and metabolites led to the identification of nine key proteins (PSB9, COA7, PFD2, CUTA, LEG1, LEG9, BET1L, CHIL3, KV5AG) as potential biomarkers and therapeutic targets for POCD. These findings emphasize the complex relationship between cognitive dysfunction, molecular alterations, and metabolic disruptions in POCD, suggesting a multifactorial pathogenesis that warrants further investigation to develop targeted interventions.

Aging involves a progressive decline in physiological function, leading to organ damage and age-related chronic diseases. Natural products derived from traditional herbs represent a valuable resource for identifying anti-aging compounds and potential lead candidates. In this study, a screen of an herbal library using Caenorhabditis elegans (C. elegans) identified the 75% ethanol extract of Callicarpa nudiflora Hook (LWLY01) as a potent lifespan-extending agent. Further fractionation revealed that its ethyl acetate extract (LWLY03) exhibited significant anti-aging activity, albeit with complex composition. Through systematic isolation and identification, verbascoside was determined to be a key active constituent. Verbascoside extended the lifespan of C. elegans and improved healthspan parameters, including motility and resistance to osmotic and thermal stress. Mutant lifespan assays demonstrated that verbascoside acts through activation of the SKN-1 signaling pathway, thereby strengthening resistance to aging-associated oxidative stress. Additionally, verbascoside was found to regulate multiple aging-related processes, such as stress response, oxidative damage, and cellular homeostasis. These findings highlight verbascoside as a promising natural compound for mitigating aging phenotypes and preventing age-related diseases.

Immunosenescence, a recognized hallmark of aging, is characterized by imbalances in immunocyte populations and a state of chronic inflammation. However, the tissue-specific dynamics of these changes and their potential as predictive biomarkers for aging remain poorly characterized. In this study, we established a multi-tissue immunological signature as a robust predictor of biological age by integrating immunocyte and cytokine profiling. Using Sprague-Dawley (SD) rats from five age groups (1-12 months), we systematically quantified 45 immunocyte subsets across peripheral blood, mesenteric lymph nodes, thymus, and spleen using flow cytometry, and profiled 22 serum cytokines/chemokines via Flexible Multi-Analyte Profiling (xMAP). Firstly, classic age-dependent shifts were observed across our rat samples, including progressive thymic involution and depletion of peripheral T-cells. Cytokine levels exhibited age-related chronic inflammation progression, marked by elevated IL-1α, granulocyte colony-stimulating factor (G-CSF), and TNF-α. To integrate these multidimensional datasets into a predictive aging metric, we employed Least Absolute Shrinkage and Selection Operator (LASSO) regression, selecting 22 biomarkers through regularization (λ = 0.111). The integrated model combining cellular and cytokine data demonstrated superior performance (training R² = 0.957, validation R² = 0.887), outperforming single-modality models based on immunocytes or cytokines. Notably, splenic parameters dominated the aging signature, contributing seven biomarkers representing 60% of model weight-particularly Th-cell expansion and Tc-cell depletion. Peripheral blood Th-cell proportion emerged as another key predictor. Our findings position the spleen as a critical aging hub and identify peripheral/splenic Th-cell modulation as promising therapeutic targets for age-related immune dysfunction, revealing novel mechanistic insights into aging-associated immune remodeling.