Biogerontology最新文献

{"title":"Tissue-specific aging clocks map structured aging-modulatory drug-score patterns across 49 human tissue and cell-line categories.","authors":"Dongdong Zhang","doi":"10.1007/s10522-026-10512-2","DOIUrl":"https://doi.org/10.1007/s10522-026-10512-2","url":null,"abstract":"<p><p>Aging clocks are typically trained on pooled multi-tissue data, implicitly assuming that aging is uniform across organs. Here we challenge this assumption by constructing 49 transcriptomic clocks across 47 tissue types and 2 cell-line categories from GTEx v8 (948 unique donors contributing to the retained clock categories) using donor-grouped cross-validation. Clocks achieved a median Pearson r of 0.543 (best: artery aorta, r = 0.855). We identified 10,253 unique clock genes, of which 69.2% appeared in only one tissue; however, null simulation confirmed that this low overlap is the expected consequence of sparse elastic-net selection rather than biological tissue-specificity. We then projected 3,926 LINCS L1000 compound-name entries onto each clock to build a drug × category age-reversal matrix. At a permissive threshold (|score|> 1.0), 94.2% of drugs showed mixed score directions (positive in some categories and negative in others). This permissive mixed-direction proportion was descriptive and did not itself exceed shuffled expectations. Under a more stringent exploratory criterion requiring |score|> 2.0 in at least three categories in each direction, 2.8% of compound entries showed pronounced bidirectional divergence, compared with approximately 0.1% under the shuffled null. Compound rankings remained stable when analysis was restricted to the 34 clocks with r ≥ 0.5 (Spearman ρ = 0.897 versus the full analysis). A Jaccard-based enrichment statistic yielded highly concordant compound rankings (median per-category Spearman ρ = 0.961), indicating that results were not artifacts of the enrichment method. After Benjamini-Hochberg FDR correction across all 192,374 drug-category pairs, only 0.79% reached FDR < 0.05, indicating that individual drug-category calls require caution. Rapamycin showed net pro-aging transcriptional signatures in our system; we explicitly emphasize that transcriptome-based scores and organismal lifespan are distinct endpoints. DepMap CRISPR analysis was repeated after GTEx-based standardization across 13 matched categories, although individual gene-level results were limited. Four statistical robustness tests confirmed model stability. These findings describe category-associated drug-score patterns and provide a tissue-aware resource for generating hypotheses about drug responses, while cautioning against over-interpretation of individual drug-category predictions without experimental validation.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging-modulatory effects of Pausinystalia macroceras (K. Schum.) Pierre polysaccharides are associated with DAF-16/FOXO and SKN-1/Nrf2 signaling in multiple aging models.","authors":"Ahequeli Gemingnuer, Xuemei Zhang, Rui Wu, Xin Meng","doi":"10.1007/s10522-026-10509-x","DOIUrl":"https://doi.org/10.1007/s10522-026-10509-x","url":null,"abstract":"<p><p>With the global aging population and increasing burden of age-related diseases, delaying aging and maintaining healthspan have become important research priorities. Aging is a complex biological process involving progressive declines in physiological function, stress resistance, proteostasis, and metabolic homeostasis, driving the development of aging modulators that target conserved longevity-associated pathways. Although pharmacological and natural aging modulators have attracted growing attention, concerns regarding the long-term safety and clinical applicability of pharmacological interventions, together with the incompletely understood mechanisms of many natural modulators, remain. Plant-derived polysaccharides are promising natural aging modulators owing to their favorable biocompatibility, low toxicity, and diverse biological activities, but their aging-modulatory effects and underlying mechanisms remain insufficiently explored. In this study, Pausinystalia macroceras (K. Schum.) Pierre polysaccharides (PMP) were found to exhibit aging-modulatory effects in both Caenorhabditis elegans and Drosophila melanogaster aging models. PMP delayed the progression of aging by extending lifespan, preserving healthspan-associated functions, and maintaining physiological fitness without adversely affecting growth, feeding behavior, or reproductive capacity. PMP also enhanced resilience to diverse environmental stresses and attenuated age-associated physiological deterioration. At the cellular level, PMP maintained redox and proteostasis homeostasis by reducing intracellular reactive oxygen species accumulation, lipofuscin deposition, and polyglutamine aggregation. These protective effects were associated with enhanced DAF-16/FOXO- and SKN-1/Nrf2-mediated longevity and stress-response signaling, accompanied by increased downstream antioxidant defenses, including SOD-3 and GST-4. PMP further alleviated age-associated metabolic disturbances by modulating amino acid, carbohydrate, and energy metabolism, indicating its ability to preserve metabolic homeostasis during aging. Overall, PMP delays aging progression in association with coordinated regulation of longevity signaling, stress resistance, proteostasis, and metabolic homeostasis, providing a mechanistic basis for its development as a natural aging-modulatory agent.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin-BDNF axis mediates muscle-brain communication: a complete molecular cascade and potential bidirectional feedback from peripheral activation to central protection.","authors":"Xiuyan Duan, Zixuan Chen, Xiangli Tong, Xuan Li, Zizi Liu, Youyi Yang, Xia Liu, Wenfeng Liu","doi":"10.1007/s10522-026-10510-4","DOIUrl":"https://doi.org/10.1007/s10522-026-10510-4","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive decline, with core pathological mechanisms including β-amyloid (Aβ) deposition, tau protein hyperphosphorylation, neuroinflammation, and impaired synaptic plasticity. Although exercise has neuroprotective effects, the molecular mechanisms by which it mediates peripheral-central communication remain unclear. The concept of the 'muscle-brain dialogue' offers a new perspective on this process. irisin, secreted by skeletal muscle in response to exercise, forms a molecular link between peripheral exercise and central neuroprotection by specifically regulating brain-derived neurotrophic factor (BDNF). This review summarizes the molecular cascade mechanisms of the irisin-BDNF axis in mediating the muscle-brain dialogue: Irisin is synthesized via the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)/fibronectin domain-containing protein 5 (FNDC5) pathway. Current evidence suggests that peripheral irisin may communicate with the central nervous system through mechanisms related to the blood-brain barrier, including potential αVβ5 integrin-mediated interactions, thereby participating in the regulation of BDNF. As a core effector molecule, BDNF improves cognitive decline in AD by enhancing neuroplasticity, reducing Aβ deposition, inhibiting tau hyperphosphorylation, and alleviating neuroinflammation. However, oxidative stress and mitochondrial dysfunction associated with AD pathology negatively regulate this axis, creating a vicious cycle. Therefore, this paper explores potential intervention strategies and the prospects for future translational research, including upstream exercise interventions, midstream barrier-crossing enhancing peptides, and downstream small-molecule TrkB agonists. Targeting this axis provides a new theoretical foundation and translational direction for the early prevention and treatment of AD, as well as for drug development.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions.","authors":"Piotr Paweł Chmielewski","doi":"10.1007/s10522-026-10506-0","DOIUrl":"10.1007/s10522-026-10506-0","url":null,"abstract":"<p><p>Mitochondria integrate bioenergetics, redox signalling, calcium handling, biosynthesis, apoptosis, and stress responses. Their contribution to ageing depends less on any single pathway than on the ability to sustain these functions through continuous maintenance, remodelling, and inter-organelle communication. This review proposes mitochondrial homeodynamics as a systems-level framework for that ability, which rests not on static preservation but on three linked capacities. Maintenance safeguards mitochondrial genome, proteome, and membrane integrity. Adaptation adjusts metabolism and remodels network and cristae architecture to match changing demand. Recovery restores function and reserve after challenge. These capacities emerge from mitochondrial quality control, network and cristae remodelling, biogenesis, mitophagy, retrograde stress signalling, and inter-organelle communication. So defined, mitochondrial dysfunction becomes a measurable loss of capacity rather than a descriptive category. Ageing erodes these capacities in tissue- and context-specific ways, which reduces physiological reserve, slows recovery after stress, and amplifies sterile inflammation. The mechanisms underlying these capacities, the biomarkers that report them, and the interventions proposed to preserve them are evaluated in turn. Exercise provides the strongest human evidence for coordinated mitochondrial and functional adaptation, whereas evidence for energy restriction, NAD+ precursors, mitophagy-supporting compounds, and mitochondria-targeted agents remains heterogeneous and endpoint-specific. No mitochondrial intervention has been shown to slow ageing or extend lifespan in healthy humans, and movement of a biomarker towards a younger reference value does not establish rejuvenation. Progress will require dynamic measures of maintenance, adaptation, and recovery, obtained in defined tissues and interpreted alongside clinically meaningful outcomes.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHCR24 regulates endothelial senescence through the SPHK2/SPNS2-S1P axis.","authors":"Wukaiyang Liang, Jinhua Yan, Han Li, Hao Nie, Jie Huang, Tianyi Ji, Zixin Wan, Yucong Zhang, Yi Huang, Le Zhang, Lei Ruan, Zhen Yang, Cuntai Zhang","doi":"10.1007/s10522-026-10505-1","DOIUrl":"https://doi.org/10.1007/s10522-026-10505-1","url":null,"abstract":"<p><p>Vascular endothelial senescence is a pivotal driver of age-related pathologies. Metabolism plays a critical regulatory role in endothelial cell senescence. Our previous studies have shown that deficiency of DHCR24, a gene involved in lipid metabolism, promotes endothelial cell senescence. However, how DHCR24 participates in endothelial cell senescence through lipid metabolism remains unclear. Using endothelial-specific DHCR24 knockout mice and replicative senescent human umbilical vein endothelial cells, we demonstrate that DHCR24 depletion significantly reduced intracellular sphingosine-1-phosphate (S1P) levels. Mechanistically, DHCR24 loss downregulated sphingosine kinase 2 (SPHK2), impairing S1P synthesis, while concurrently upregulating the S1P transporter (SPNS2), enhancing S1P export. Critically, SPHK2 overexpression rescued senescence phenotypes in DHCR24-deficient cells. SPHK2 knockdown recapitulated SPNS2 upregulation and endothelial senescence, whereas pharmacological inhibition of SPNS2 with 16d attenuated SPHK2 knockdown-induced increases in p16, p21 and SA-β-gal activity, and restored eNOS expression and nitric oxide (NO) production. In vivo, endothelial-specific DHCR24 knockout increased circulating S1P levels, and plasma S1P was positively correlated with pulse wave velocity in humans. Collectively, these findings suggest the DHCR24-SPHK2/SPNS2-S1P axis as an important pathway involved in endothelial senescence.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global evidence for bounded human lifespan growth.","authors":"Marta Gonçalves, Byung Mook Weon","doi":"10.1007/s10522-026-10499-w","DOIUrl":"https://doi.org/10.1007/s10522-026-10499-w","url":null,"abstract":"<p><p>Is there a limit to human lifespan? We examine upper-tail lifespan dynamics in 46 countries using reliable period life-table data. The characteristic life ( <math><mi>α</mi></math> ), the model-based upper-tail parameter ( <math><mi>ω</mi></math> ), and their interval ( <math><mrow><mi>δ</mi> <mo>=</mo> <mi>ω</mi> <mo>-</mo> <mi>α</mi></mrow> </math> ) are estimated annually from the 1990s onward. Across countries, <math><mi>α</mi></math> increases steadily, whereas <math><mi>ω</mi></math> declines or stabilizes and <math><mi>δ</mi></math> narrows, a pattern consistent with postponed and increasingly concentrated late-life mortality rather than unlimited upper-tail expansion. Under the baseline <math><mrow><mi>L</mi> <mo>=</mo> <mn>120</mn></mrow> </math> projection model, both females and males approach <math><mrow><mi>ω</mi> <mo>≈</mo> <mn>120</mn></mrow> </math> years and <math><mrow><mi>α</mi> <mo>≈</mo> <mn>103.5</mn></mrow> </math> years by 2100. Sensitivity analyses show that the inferred asymptotic boundary is model-dependent, so the projected value near 120 years should be interpreted as a mathematical upper-tail estimate rather than a definitive biological maximum. These findings are consistent with, but do not establish, an increasingly bounded upper-tail survival regime within the present demographic and modeling framework.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress biology and metabolic ageing in older adults during prolonged crises: Ukraine as an example.","authors":"Oleh Lushchak, Olha Strilbytska, Pavlo Petakh, Oleksandr Kamyshnyi","doi":"10.1007/s10522-026-10502-4","DOIUrl":"https://doi.org/10.1007/s10522-026-10502-4","url":null,"abstract":"<p><p>Prolonged crises expose older adults to chronic psychological and social stress, irregular nutrition, reduced physical activity, reduced access to health care, and interruptions in treatment of chronic disease. Together, these factors can compound age-related vulnerabilities and increase the risk of metabolic deterioration, multimorbidity and functional decline. This Perspective argues that prolonged crises should be viewed not only as social or psychological events, but also as conditions that may affect stress-related and ageing-related biological pathways. Severe or prolonged stress, however, can make these responses maladaptive and contribute to physiological dysregulation. Under prolonged crisis conditions, such maladaptive stress responses may be linked to abdominal obesity, sarcopenic obesity, physical frailty, and functional decline through chronic activation of the hypothalamic-pituitary-adrenal axis, altered glucocorticoid signalling, sleep disturbance, inflammation, cellular senescence and senescence-associated secretory phenotype, immunometabolic dysregulation, adipose tissue inflammation, insulin resistance, mitochondrial dysfunction and anabolic resistance in skeletal muscle. Ukraine is a timely example of this broader problem, as prolonged war, population ageing, non-communicable diseases, displacement, mental health needs, and new screening initiatives now intersect. Thus, a biologically informed framework for healthy ageing needs to incorporate mental health assessment, metabolic screening, nutritional assessment, muscle function and rehabilitation rather than address these in isolation. Functional ability reflects the combined effects of psychological stress, metabolic ageing, muscle loss, multimorbidity, and changes in the living environment. It should be considered a key indicator for older adults during and after prolonged crises.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating pharmacological targeting of actin regulatory pathways during aging in C. elegans.","authors":"Tiffany Wang, Athena Alcala, Daniella Berdan, Veronica Kuo, Gilberto Garcia, Ryo Higuchi-Sanabria, Maxim Averbukh","doi":"10.1007/s10522-026-10503-3","DOIUrl":"10.1007/s10522-026-10503-3","url":null,"abstract":"<p><p>Actin is a highly conserved cytoskeletal protein that regulates numerous cellular processes essential for tissue homeostasis and healthy aging. Although genetic studies have established important roles for actin and actin-binding proteins in longevity, pharmacological approaches offer complementary advantages for manipulating conserved cytoskeletal pathways across model systems. Here, we systematically evaluated the effects of small-molecule modulators targeting distinct actin regulatory pathways on lifespan, locomotor function, and tissue-specific actin organization in Caenorhabditis elegans. Animals were treated with compounds targeting the Arp2/3 complex (CK666), tropomyosin-dependent actin regulation (TR100), formins (SMIFH2), cofilin regulation (SZ-3), or actin stabilization (phalloidin). Among the compounds tested, only CK666 consistently produced a dose-dependent reduction in lifespan and exacerbated age-associated muscle actin disorganization, identifying Arp2/3-mediated actin branching as a critical regulator of cytoskeletal integrity during aging. CK666 also transiently disrupted hypodermal actin organization early in adulthood. In contrast, SMIFH2, TR100, phalloidin, and SZ-3 produced little or no detectable disruption of muscle actin organization, despite previous genetic studies demonstrating roles for several of these pathways in aging. Comparison with prior RNAi studies suggests that pharmacological perturbation can reproduce some aspects of actin dysfunction but may be limited by compound stability, drug delivery, or inefficient targeting of proteins in C. elegans. Together, these findings establish a framework for evaluating pharmacological modulation of actin during aging, identify CK666-mediated Arp2/3 inhibition as the most robust pharmacological perturbation under the conditions tested, and highlight important considerations for translating genetic discoveries into pharmacological strategies to target cytoskeletal function during aging.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.","authors":"Ertan Kanbur, Omer Aydin","doi":"10.1007/s10522-026-10489-y","DOIUrl":"https://doi.org/10.1007/s10522-026-10489-y","url":null,"abstract":"<p><p>Cellular senescence, a hallmark of aging, entails the irreversible cessation of cell division in response to intrinsic and extrinsic stressors. Though metabolically active, senescent cells lose their replicative capacity and resist apoptotic signals, accumulating tissues with advancing age and contributing to age-related pathologies. Senescence is characterized by the acquisition of a senescence-associated secretory phenotype (SASP), releasing a myriad of bioactive molecules. SASP not only influences intracellular processes but also orchestrates the modification of neighboring cells and the surrounding microenvironment. In the context of aging, the proportion of senescent cells escalates, ranging from 1 to 15% in different species, tissues, and activity levels. This accumulation is associated with age-related diseases and morbidity. Beyond aging, senescence induction is observed in response to cancer treatments, including radiotherapy and chemotherapy, potentially contributing to cancer metastasis and recurrence. Consequently, the exploration of senolytic therapies aimed at eliminating senescent cells has gained considerable momentum. Addressing the limitations of free therapeutics, nano-drug delivery systems have been meticulously engineered to enhance solubility, stability, and targeted delivery. These nanocarriers overcome challenges related to poor bioavailability, uncontrolled biodistribution, and off-target effects, thereby improving therapeutic efficacy and safety. Precise control over nanoparticle size and uniformity enables targeted distribution, enhancing therapeutic precision. While nanomedicine is revolutionizing healthcare, its potential to mitigate cellular senescence remains largely unexplored despite extensive cancer research. This comprehensive review aims to consolidate the current understanding of cellular senescence and its pathological consequences. Furthermore, we present an in-depth analysis of studies employing nano-drug delivery systems in cellular senescence research, emphasizing their potential role and prospects in this evolving scientific landscape. This research is a significant step towards filling this gap and paving the way for future advancements in the field.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine and its derivatives as candidate modulators of immunosenescence: a critical evaluation.","authors":"Roman A Zinovkin, Konstantin G Lyamzaev, Alexey Churov, Olga Maltseva, Zhenghi Wu","doi":"10.1007/s10522-026-10504-2","DOIUrl":"https://doi.org/10.1007/s10522-026-10504-2","url":null,"abstract":"<p><p>Berberine has been widely used in traditional and folk medicine for many years. The molecular mechanisms of berberine's action are pleiotropic and have been fairly well studied. Its applications are generally limited to cardiometabolic diseases and cancer therapy, and a focused critical evaluation of berberine and its derivatives in the specific context of immunosenescence remains limited. Immunosenescence represents an age-associated remodeling of the innate and adaptive immune systems, closely linked to impaired immunometabolism, chronic inflammation, and shifts in the AMPK/mTOR, NF-κB, autophagy, and inflammasome pathways; therefore, berberine is a logical candidate for the role of a multi-target regulator of these processes. In this review, we examine the molecular mechanisms of immunosenescence and their biomarkers, and critically evaluate the effects of berberine on these parameters. Here we provide a detailed examination of the rationale for using berberine as a modulator of immunosenescence and proposes a design for future studies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}