Rejuvenation Research

Growth Differentiation Factor 15 (GDF-15) is closely associated with the occurrence and progression of sarcopenia, but the causal relationship between GDF-15 and sarcopenia remains unclear, and it is also uncertain whether immune cells mediate the pathway between GDF-15 and sarcopenia. We employed Mendelian randomization analysis to explore the causal relationship between GDF-15 and sarcopenia, using the inverse variance-weighted (IVW) method as the primary analytical approach, and validated the results through sensitivity analyses. In addition, we explored whether 731 immune cell phenotypes mediate these causal relationships. GDF-15 was negatively correlated with all four traits of sarcopenia, specifically with whole body fat-free mass (odds ratio [OR] = 0.989, 95% confidence interval [CI] = 0.979–0.998, p_IVW = 2.149E−02), left arm fat-free mass (OR = 0.988, 95% CI = 0.979–0.998, p_IVW = 1.345E−02), right arm fat-free mass (OR = 0.987, 95% CI = 0.979–0.995, p_IVW = 1.091E−03), and appendicular lean mass (OR = 0.984, 95% CI = 0.974–0.993, p_IVW = 7.658E−04). Mediation analysis indicated that CD127 on CD28⁺ CD45RA⁺ CD8^br mediated the causal relationship between GDF-15 and sarcopenia, with a mediation proportion of 21.58% (p = 0.023). In conclusion, our study proposed that CD127 on CD28⁺ CD45RA⁺ CD8^br mediates the causal relationship between GDF-15 and sarcopenia, providing potential theoretical support and practical guidance for the innovation of treatment strategies and personalized therapies for sarcopenia.

The Geriatric Nutritional Risk Index (GNRI) is widely used to assess nutritional status. However, its association with postoperative cognitive dysfunction (POCD) and postoperative complications in elderly patients receiving total hip arthroplasty remains inadequately explored. GNRI was calculated based on serum albumin and body weight. POCD was diagnosed using the Z-score method based on cognitive test performance on the seventh postoperative day. Glial fibrillary acidic protein (GFAP) and S100β levels were determined using an enzyme-linked immunosorbent assay. A Receiver Operating Characteristic curve was performed to evaluate the predictive value of GNRI. Multivariate logistic regression was conducted to identify risk factors for POCD in elderly patients undergoing total hip arthroplasty. The POCD group was significantly older, had lower educational attainment, longer surgery duration, greater intraoperative blood loss, and lower preoperative GNRI scores compared to the non-POCD group. Preoperative GNRI demonstrated moderate predictive value for POCD, with an area under curve (AUC) of 0.78. Multivariate logistic regression analysis identified age (odds ratio [OR]: 1.214, 95% confidence interval [CI]: 1.047–1.449), blood loss (OR: 1.198, 95% CI: 1.055–1.493), and anesthesia duration (OR: 1.376, 95% CI: 1.112–1.795) as significant risk factors for POCD, while preoperative GNRI (OR: 0.885, 95% CI: 0.768–0.973) was identified as a protective factor. POCD patients exhibited significantly lower Montreal Cognitive Assessment (MoCA) scores and higher serum S100β and GFAP levels than the non-POCD group. Preoperative GNRI was positively correlated with MoCA scores (r = 0.46, p < 0.001) and negatively correlated with serum S100β (r = −0.43, p < 0.001) and GFAP (r = −0.37, p < 0.001) levels. Higher preoperative GNRI scores were associated with a reduced incidence of postoperative complications, including pulmonary infections and liver dysfunction. Preoperative GNRI serves as an effective predictor of POCD and postoperative complications in elderly patients receiving hip arthroplasty.

Pancreatic cancer (PC) is a highly lethal malignancy with significant drug resistance and recurrence. This study explores the molecular mechanisms by which resveratrol (RES) inhibits PC proliferation, invasion, and migration, aiming to provide new insights for future therapeutic strategies. Network pharmacology was used to construct a component-pathway-target network diagram for the effect of RES on PC. Transwell assays were used to analyze cell invasion. In addition, scratch assays were conducted to evaluate cell migration ability, and qPCR was utilized to monitor the mRNA expression levels of genes. Immunofluorescence and Western blotting were applied to detect protein expression. The results demonstrate that RES exhibits a significant inhibitory effect on PC cells at different concentrations, with 50 μmol/L RES showing the most pronounced inhibition. This observation was further confirmed by Transwell and scratch assays, which showed that RES significantly inhibits PC cell proliferation, invasion, and migration. Network pharmacology analysis suggests that RES may act on the Rap1 pathway to suppress the progression of PC. In vitro experiments confirmed that RES downregulates the expression of CDC42, MMP2, and MMP9. Notably, immunoprecipitation experiments revealed that RES induces the succinylation of CDC42, which, in turn, inhibits the CDC42 signaling pathway. This disruption leads to the destabilization of the extracellular matrix (ECM), thereby impeding tumor progression. This study demonstrates that RES significantly inhibits the proliferation, invasion, and migration of PC cells by mediating the succinylation of CDC42, which in turn inhibits the CDC42 signaling pathway and disrupts the dynamics of the ECM. This mechanism highlights the potential of RES as an anticancer agent and provides new insights for the development of therapeutic strategies for PC.

Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, is a fundamental challenge affecting both invertebrate and vertebrate organisms. Environmental triggers such as pollutants, heavy metals, pesticides, and seasonal fluctuations, alongside endogenous factors like heme metabolism and disease, contribute to elevated ROS production across animal taxa. These molecular species can damage proteins, membranes, and nucleic acids, compromising cellular integrity and function. The aim of this study is to comprehensively observe and compare the impact of oxidative stress on invertebrates (including protozoa, annelids, arthropods, and mollusks) and vertebrates (fish, amphibians, birds, and mammals), elucidating common and distinct stress pathways. Using integrative evidence from schematic representations and biological pathways, this work highlights conserved mechanisms such as lipid peroxidation, Fenton chemistry, and the upregulation of defense enzymes. Despite evolutionary divergence, the findings demonstrate that oxidative stress responses are universally pivotal in regulating cellular homeostasis, inflammation, and survival. The study underscores the importance of redox balance in animal adaptation and health, offering insight into stress physiology and potential targets for mitigating oxidative damage in diverse species.