Rejuvenation research最新文献

{"title":"Impact of Metformin on Healthspan-Related Outcomes and Incidence of Diseases of Aging in People with Type 2 Diabetes Mellitus: A Systematic Review.","authors":"Amy Hai Yan Chan, Kebede Beyene, Bertha Lai, Sarah Kim, Ivy Wu, Rana Al-Jawadi, Margaret Wu, Holly Foot, Gary Cheung, Xaviour Walker, Yoram Barak","doi":"10.1177/15491684261462413","DOIUrl":"https://doi.org/10.1177/15491684261462413","url":null,"abstract":"<p><p>Metformin use may be associated with reduced risk of all-cause mortality as well as prevent the onset of diseases of aging, namely cardiovascular diseases (CVD), cancer, and dementia. We systematically reviewed recent studies to determine whether metformin can promote healthspan in people with type 2 diabetes mellitus (T2DM). A comprehensive literature search was conducted using Medline, Embase, and Scopus for randomized controlled trials (RCTs) and cohort studies evaluating the effect of metformin on the incidence of all-cause mortality. Publications investigating metformin's effects on CVD, cancer or dementia were included. Search was restricted to English-only publications between 2016 and 2021. Full-text review, data extraction, and assessment of risk of bias using the Newcastle-Ottawa Scale were undertaken. Of 130 articles reviewed, 27 met the inclusion criteria. All 27 studies are observational cohorts, and no RCTs met the inclusion criteria, so causality cannot be inferred. No RCTs met the inclusion criteria. Five studies investigated the effects of metformin on all-cause mortality, 17 on the incidence of cancer, 3 on CVD, and 4 on dementia. Data heterogeneity precluded meta-analysis. Included studies were of high quality with NOS scores of 6-9. Metformin use in individuals with T2DM was associated with reduced risk of all-cause mortality, incidence of CVDs, and dementia. Metformin was associated with a reduced risk of prostate cancer but otherwise effects varied with cancer type and remain inconclusive.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"15491684261462413"},"PeriodicalIF":2.6,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274129","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":"Nerolidol Mitigates 3-Nitropropionic Acid-Induced Neurotoxicity: <i>In Silico</i>, <i>In Vitro</i>, and <i>In Vivo</i> Approach.","authors":"Ritika Devi, Dhirendra Shukla, Vishal Kumar, Shubham Upadhayay, Kailash Jangid, Vinod Kumar, Puneet Kumar","doi":"10.1177/15491684261449703","DOIUrl":"https://doi.org/10.1177/15491684261449703","url":null,"abstract":"<p><p>Huntington's disease (HD) is an inherited hyperkinetic movement disorder allied with chorea, cognitive impairment, and psychological disorders. Nerolidol (NRD) is a natural sesquiterpene alcohol obtained from many plants that has been shown to display neuroprotective properties. The current study focused on investigating the mechanism behind the neuroprotective role of NRD against 3-nitropropionic acid (3-NP)-induced neurotoxicity in experimental animals. Initial prediction was carried out through computational modeling (<i>in silico</i>), followed by a series of <i>in vitro</i> and <i>in vivo</i> experiments utilizing batteries of behavioral and molecular tests. Molecular docking was performed using Schrödinger (Maestro 2.0) to further explore NRD's neuroprotective capacity against 3-NP-induced neurotoxicity in SH-SY5Y cell lines and rats. For the <i>in vivo</i> study, 24 adult Wistar rats were randomly divided into four different groups, while NRD (50 and 100 mg/kg) was chosen to study their neuroprotective impact against HD-like symptoms utilizing different behavioral, biochemical, and histopathological parameters. <i>In silico</i> studies demonstrated that NRD has a high binding affinity for active sites of targeted enzymes, while <i>in vitro</i> data showed that NRD can counteract the neurotoxic effects of 3-NP in SH-SY5Y cells. NRD therapy (50 and 100 mg/kg) significantly improved motor activity, levels of malondialdehyde and glutathione, and histopathological changes. The findings revealed that NRD offers antioxidant and neuroprotective effects against 3-NP-induced neurotoxicity. The observed results indicated that NRD may exert its effects by activating the Nrf2 and heme oxygenase-1 pathways. Thus, it is suggested that it may be employed as an alternative treatment to fight against neurotoxicity.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"15491684261449703"},"PeriodicalIF":2.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201864","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":"Agrin as a Stable Biomarker for Muscle Strength Decline in Elderly Sarcopenic Patients Associated with Neuromuscular Junction Dysfunction.","authors":"Jihai Chen, Nuo Cheng, Ye Liu, Tongtong Xu, Ling Xi, Cong Wang, Xiaojun Ouyang","doi":"10.1177/15491684251410100","DOIUrl":"10.1177/15491684251410100","url":null,"abstract":"<p><p>Agrin-mediated neuromuscular junction (NMJ) morphological alterations is one of the main pathogeneses of sarcopenia. The aim of this study was to observe the changes in serum agrin in patients with different degrees of sarcopenia and the alterations in Agrin receptors in human skeletal muscle with age. A total of 236 elderly subjects were enrolled and categorized into nonsarcopenia, possible sarcopenia, sarcopenia, and severe sarcopenia groups. Serum levels of the C-terminal Agrin fragment were quantified using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. In addition, in a distinct and smaller exploratory subgroup (<i>n</i> = 12), quantitative real-time polymerase chain reaction and immunofluorescence staining were performed to investigate the expression of Agrin receptors, specifically low-density lipoprotein receptor-related protein 4 (Lrp4) and alpha-dystroglycan (α-DG), in human skeletal muscle samples. Compared with that in the nonsarcopenia group, the level of agrin in the other groups was significantly different. Partial correlation analysis and binary logistic regression analysis suggested that the level of Agrin was associated with handgrip strength. There was a significant increase in the serum level of agrin and a reduction in the mRNA expression of the agrin receptors <i>Lrp4</i>, <i>α-DG,</i> and <i>RAPSN</i>, while immunofluorescence analysis confirmed the expression patterns of the Lrp4 and α-DG receptors. In the elderly population, the level of agrin decreased in patients with sarcopenia, while the expression of its receptors also decreased. These factors result in NMJ morphological alterations, weakened muscle contraction, and increased risk of sarcopenia.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":"29 3","pages":"123-130"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679818","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":"Nicotinamide Mononucleotide Reduces Iron in BV-2 Cell by Up-Regulating Ferroportin 1 via Inhibiting the IL-6/STAT3/Hepcidin Pathway.","authors":"Zhong-Ming Qian, Huimin Ma, Yun-Jin Chen, Qian Guo","doi":"10.1177/15491684251405189","DOIUrl":"10.1177/15491684251405189","url":null,"abstract":"<p><p>Findings on the association of both nicotinamide mononucleotide (NMN) and iron metabolism with antiaging or aging led us to speculate that some pharmacological functions of NMN may be achieved partially by affecting iron metabolism. Here, we investigated the effects of NMN on cell viability, iron contents, oxidative stress, and the expression of ferritins, transferrin receptor 1 (TfR1), ferroportin1 (Fpn1), hepcidin, interleukin 6 (IL-6), interleukin-1β (IL-1β), and signal transducer and activator of transcription 3 (STAT3) in BV2 microglia (BV-2) cells treated with 150 μM of ferric ammonium citrate. We found that NMN induced a significant reduction in iron concentration, ferritin expression, and reactive oxygen species level, and an increase in cell viability in iron-overloaded BV-2 cells. Also, NMN significantly up-regulated TfR1 and down-regulated Fpn1 and hepcidin expression as well as IL-6, IL-1β, and pSTAT3 contents in iron-overloaded BV-2 cells. We concluded that NMN is able to regulate the expression of iron transport proteins TfR1 and Fpn1, via IL6/STAT3/hepcidin and IL-1β/hepcidin pathways, and then down-regulate iron contents and the expression of ferritin and inhibit oxidative stress in iron-overloaded BV-2 microglia cells, supporting that some pharmacological functions of NMN may be partly associated with the effects of NMN on iron metabolism. Our results suggest that NMN may have beneficial therapeutic effects on iron-related diseases such as neurodegenerative diseases.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"85-93"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679894","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":"Identifying Potential Drug Targets in the Knee Osteoarthritis: Insights from the Druggable Genome.","authors":"Chiyun Sun, Ruikang Liu, Weiming Fan, Jiaming Hu, Chuanrui Sun, Kaiqiang Tang, Pengcheng Shan, Hongmei Zhang","doi":"10.1177/15491684251403435","DOIUrl":"10.1177/15491684251403435","url":null,"abstract":"<p><p>The aim of this study was to find potential drug targets of knee osteoarthritis (KOA) through druggable genome and Mendelian randomization (MR) analysis. Through integrating data from expression quantitative trait loci at different tissue and cellular levels, we identified potential therapeutic targets for KOA using drug target MR and single-cell MR analyses. Based on peripheral protein quantitative trait locus (pQTL) data, we validated the identified targets at the proteomic level using summary data-based MR and Heterogeneity in Dependent Instrument tests. Meanwhile, we used mediation MR analysis to explore possible mechanisms of action of the identified targets in KOA. To capture tissue specificity, we further applied the genetically informed spatial mapping (gsMap) framework, integrating KOA genome-wide association studies with spatial transcriptomics of E16.5 mouse embryonic tissues. We identified 12 and 5 potential therapeutic targets for KOA from peripheral and central tissues, respectively. Mitogen-activated protein kinase (MAPK3) and MARK3 were validated at the proteomic level, with MAPK3 showing a genetic association with reduced risk against KOA in both peripheral and central tissues. Single-cell MR analysis revealed that Lymphocyte antigen 6 D (LY6D) was associated with an increased risk of KOA in exogenous cells, MAPK3 showed a protective association in inhibitory neuron cells, and transforming growth factor alpha (TGFA) was associated with a reduced risk of KOA in oligodendrocyte precursor cells. Mediation MR analysis showed that body mass index (BMI) played a 16.6% mediating role in the causal association between MAPK3 and KOA. GsMap analysis revealed significant enrichment of KOA signals in cartilage primordium, cartilage, lung, and brain tissues. Finally, we proposed 16 potential therapeutic targets for KOA from both central and peripheral perspectives. Meanwhile, we found that BMI served as a mediator to mediate the causal effect between MAPK3 and KOA. Further experiments are needed in the future to verify the mechanism of action of the targets identified in this study in KOA.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"94-105"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852157","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":"Naomaili Granules Attenuate Cerebral Ischemia/Reperfusion Injury by Inhibiting Endoplasmic Reticulum Stress and RhoA/Pyrin Signaling Pathway.","authors":"Hao Fang, Ling-Ling Fan, Jia-Yi Zheng, Yu-Hui Qiu, Rong-Rong Zhang, Xiaogang Li, Huang Yan, Ye-Feng Cai, Shi-Jie Zhang, Li-Jun Qiao","doi":"10.1177/15491684251405810","DOIUrl":"10.1177/15491684251405810","url":null,"abstract":"<p><p>Ischemic stroke (IS) is the worldwide leading cause of death and disability, so finding new approaches to prevent and treat IS has become urgent. Naomaili granules (NML), a proprietary Chinese medicine modified from Buyang Huanwu Decoction, has significant beneficial effects in treating IS. The present study demonstrated that NML significantly narrowed the volume of cerebral infarction in rats after middle cerebral artery occlusion (MCAO)/reperfusion (R), and in addition, improved their neurological function and reduced neuronal cell damage. Moreover, NML suppressed endoplasmic reticulum (ER) stress in MCAO/R rats and attenuated cellular pyroptosis by inhibiting the Ras Homolog Family Member A (RhoA)/pyrin pathway. In conclusion, the present study demonstrated that cerebral ischemia/reperfusion-induced ER stress in rat cortical neurons and may mediate pyroptosis of the cortical neurons through RhoA/pyrin. Meanwhile, NML reduced neuronal death and improved neurological function in rats by inhibiting ER stress and the RhoA/pyrin cellular pathway.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"106-122"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835586","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":"Synergistic Neuroprotective Effects of Taurine and Tauroursodeoxycholic Acid on the Neurovascular Unit in Hypoxia-Reoxygenation Injury.","authors":"Xin Du, Shi-Yong Li, Guang-Liang Wu, Hai-Yan Cai, Chun-Yan Sun, Hao Lin, Ye-Feng Cai, Qingguo Wang","doi":"10.1177/15491684251409076","DOIUrl":"10.1177/15491684251409076","url":null,"abstract":"<p><p>Taurine and tauroursodeoxycholic acid are used for treating cerebral ischemia. In this study, we used the combination of taurine and tauroursodeoxycholic acid to establish a model of ischemia-reperfusion injury and evaluate the effect and target of the drug combination using the neurovascular unit (NVU) model of hypoxia and reoxygenation <i>in vitro</i>. Results showed that the combined application of these two drugs improved the survival of neurons, astrocytes, and endothelial cells; reduced inflammatory damage, levels of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1β, oxidative stress response, and the release of malondialdehyde and nitric oxide; and enhanced the activity of superoxide dismutase. Simultaneously, they acted on the blood-brain barrier (BBB) and improved the transendothelial electrical resistance value, reduced lactate dehydrogenase levels, improved the activity of γ-glutamyl transferase, and protected the integrity of the BBB against damage caused by oxygen-glucose deprivation/reoxygenation. At the same time, they prevented neuronal apoptosis, reduced the expression of Bax and caspase-3, and increased the expression of Bcl-2. These two drugs regulated the expression of connexin 43 (CX43) and aquaporin 4 (AQP4) in astrocytes, reducing the level of AQP4, and improving the activity of CX43. In addition, the drug combination increased the expression of tight junction proteins in endothelial cells, such as zona occludens-1, occluding, and claudin-5, and decreased the expression of matrix metalloproteinase (MMP)2 and MMP9. Furthermore, they acted together on the p38 mitogen-activated protein kinase (MAPK) signaling pathway, and the addition of the p38 inhibitor SB203580 partially inhibited the expression of p38MAPK. Thus, the combined action of these drugs protected the NVU.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"131-145"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127996","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":"Regular Daily Exercise Improves Sarcopenia in Elderly Patients.","authors":"Jiachuang Zheng, Hui Luo, Zhixia Zheng, Shan Wang, Ting Mo, Yuxia Ma","doi":"10.1177/15491684261449707","DOIUrl":"https://doi.org/10.1177/15491684261449707","url":null,"abstract":"<p><p>Sarcopenia attenuates independence and mobility in older adults, and scalable nonpharmacological interventions are needed. This trial evaluated whether a 12-week exercise program improves activities of daily living, muscle mass and strength, physical performance, and systemic inflammation in older adults with sarcopenia. In this 12-week randomized controlled trial, adults aged 60-75 years with sarcopenia were randomized 1:1 to a control group or an exercise group. The exercise group performed postprandial multicomponent training (37 min/session, 3 days/week), combining resistance and aerobic exercise. Outcomes were measured at baseline and at week 12. The primary endpoint was the Modified Barthel Index (MBI). Secondary endpoints were Appendicular Skeletal Muscle Mass Index (ASMI), handgrip strength, the 6-minute walk test (6MWT), the Timed Up and Go Test (TUGT), and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Of 224 enrolled participants, 120 were randomized and 94 were analyzed (control, <i>n</i> = 49; exercise, <i>n</i> = 45). At week 12, the exercise group showed higher MBI (68.89 ± 9.60 vs. 62.02 ± 10.35; <i>p</i> = 0.001), ASMI (6.074 ± 0.904 vs. 5.295 ± 0.739 kg/m²; <i>p</i> < 0.001), and handgrip strength (22.78 ± 5.02 vs. 19.95 ± 4.25 kg; <i>p</i> = 0.009); better 6MWT (395.6 ± 55.6 vs. 363.7 ± 53.8 minutes; <i>p</i> = 0.005), shorter TUGT (6.76 ± 1.41 vs. 7.66 ± 1.55 seconds; <i>p</i> = 0.005), and lower IL-6 (45.21 ± 10.66 vs. 53.73 ± 10.99 pg/mL; <i>p</i> < 0.001) and TNF-α (38.09 ± 8.64 vs. 45.45 ± 8.07 pg/mL; <i>p</i> < 0.001) compared with the control group. These findings suggested that a 12-week regular exercise program improved functional independence, muscle health, mobility, and inflammatory status in older adults with sarcopenia.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"15491684261449707"},"PeriodicalIF":2.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848055","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":"Hypothesis: Glyoxal Is an Unavoidable Byproduct of the Activity of Transketolase in the Pentose Phosphate Pathway.","authors":"Benjamin Szwergold","doi":"10.1177/15491684251396532","DOIUrl":"10.1177/15491684251396532","url":null,"abstract":"<p><p>Diabetes mellitus and its consequent pathological complications continue to pose serious and growing health care challenges across the world. One promising mechanism for linking hyperglycemia and diabetic complications is the process of spontaneous, nonenzymatic reactions between glucose and its catabolites with amino groups in macromolecules (a.k.a. Maillard reactions). The most reactive sugars in this process are two low-molecular-weight α-dicarbonyls: methylglyoxal and glyoxal (GO). While the origins of methylglyoxal are well documented, little is known about the origins of the equally important GO. This article postulates that GO is produced as an unavoidable byproduct of the transketolase reaction in the pentose-phosphate pathway.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"57-61"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552577","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":"Immunoglobulin G and Aging: Biological Functions and Its Crosstalk with the Gut Microbiota.","authors":"Xin-Yi Zhang, De-Guan Li","doi":"10.1177/15491684251396176","DOIUrl":"10.1177/15491684251396176","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"73-79"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574914","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}