Biogerontology最新文献

{"title":"Established determinants of replicative lifespan, including mitochondrial DNA, play a limited role in early yeast stress-resistance decline.","authors":"Aglaia V Azbarova, Kseniia V Galkina, Dmitry A Knorre","doi":"10.1007/s10522-026-10528-8","DOIUrl":"https://doi.org/10.1007/s10522-026-10528-8","url":null,"abstract":"<p><p>Baker's yeast is a long-standing model for studying mechanisms of aging. Due to asymmetric division, yeast mother and daughter cells are distinguishable, and mother cells usually cease division after 15-25 budding events. However, yeast suspensions consist predominantly of young cells. Here we investigated whether, under harsh environmental conditions, replicative aging-defined by the number of buds produced-manifests at early replicative ages. To test this, we adapted a flow-cytometry-based pulse-chase labeling method to track the survival of cells of increasing replicative age, from daughter cells to mother cells that had produced up to eight buds on average. We found that stress-induced mortality increased with replicative age across all nine stress conditions tested. Mitochondrial dysfunction, caused by depletion of mitochondrial DNA, altered basal stress resistance for some stresses but largely preserved the age-dependent decline in stress resistance across conditions. Similarly, deletion of FOB1, which extends replicative lifespan under optimal conditions, did not markedly alter this decline under heat shock or acetic acid. In contrast, deletion of SIR2, which shortens replicative lifespan, steepened the age-mortality slope under acetic acid stress but not under heat shock. Together, our data indicate that aging manifests early in life under various extreme environments, and that the genetic determinants of maximum replicative lifespan tested here are largely dispensable for the early decline in stress resistance.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223266","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":"Effects of Finasteride exposure on lifespan and locomotor phenotypes.","authors":"Keyao Long, Keyi Mo, Kai Xu, Xiaojing Yang, Xiangmin Xu, Su Wang, Menglong Rui","doi":"10.1007/s10522-026-10529-7","DOIUrl":"https://doi.org/10.1007/s10522-026-10529-7","url":null,"abstract":"<p><p>Finasteride is one of the core medications for treating androgen-associated diseases in men. It exhibits multiple therapeutic functions, including inhibiting 5α-reductase, reducing dihydrotestosterone levels, and improving conditions, including prostate enlargement and hair loss. Using Drosophila as the primary model and a mouse behavioral assay as a complementary approach, we combined developmental and behavioral assessments, morphological analyses of motor and sensory neurons, transcriptomics, and genetic methods to investigate developmental, neuronal, and behavioral changes associated with Finasteride exposure and explore their potential molecular basis. Our results indicate that Finasteride exposure is associated with increased intestinal reactive oxygen species (ROS) accumulation and shortened lifespan in both sexes, together with significantly reduced starvation resistance in males. In addition, Finasteride exposure was also associated with altered neuromuscular junction (NMJ) morphology, reduced locomotor performance, and decreased cask expression. Motor-neuron CASK overexpression improved NMJ morphology and locomotor performance in Finasteride-exposed flies. Overall, this study reveals changes in lifespan and locomotor phenotypes associated with Finasteride exposure and further highlights the importance of investigating its broader biological effects in other experimental systems.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214928","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":"Quantitative assessment of liver regenerative potential during accelerated aging: regenerative reserve and regenerative status indices.","authors":"David A Areshidze, Maria A Kozlova, Anna I Anurkina, Alexey Moskalev","doi":"10.1007/s10522-026-10527-9","DOIUrl":"https://doi.org/10.1007/s10522-026-10527-9","url":null,"abstract":"<p><p>Age-related changes in hepatocyte ploidy, binucleation, proliferative activity, and senescence-associated cell-cycle arrest may jointly influence liver regenerative capacity, but these features are usually evaluated separately. We developed two composite indices and examined their behavior in a long-term rat model of chronic circadian disruption. Male Wistar rats were assigned to control lighting, constant illumination (dark deprivation; DD), or constant illumination with melatonin (DD + melatonin, 10 mg/kg five times weekly) and assessed at 6, 12, 18, and 24 months. The Index of Regenerative Reserve (IRR) was defined as the proportion of binucleated hepatocytes divided by mean hepatocyte ploidy. The Integrated Index of Regenerative Status (IRS) further incorporated Ki-67 (a marker of active cell proliferation) and p21 (a cyclin-dependent kinase inhibitor associated with cell-cycle arrest) as fractional terms: IRS = IRR × (1 + Ki-67)/(1 + p21).In DD animals, IRR declined from 2.00 ± 0.42 at 6 months to 0.386 ± 0.19 at 24 months; the corresponding 24-month IRS was 0.32 ± 0.17. In DD + melatonin animals, 24-month IRR and IRS were 2.285 ± 0.41 and 2.08 ± 0.16, respectively. Exploratory receiver-operating-characteristic analysis yielded areas under the curve of 0.843 for IRR and 0.905 for IRS. These findings support IRR and IRS as experimental composite descriptors of the hepatic regenerative phenotype. External validation and direct functional regeneration assays are required before broader biological or clinical interpretation.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191359","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":"Oxidative stress resistance of the extended longevity phenotype of Drosophila under paraquat exposure is heritable: influence of maternal genotype on the offspring.","authors":"S Deepashree, T Shivanandappa","doi":"10.1007/s10522-026-10523-z","DOIUrl":"https://doi.org/10.1007/s10522-026-10523-z","url":null,"abstract":"<p><p>Oxidative stress resistance is an important trait that contributes to the long lifespan of Drosophila melanogaster, but its epigenetic inheritance via transgenerational transmission has been poorly studied. In this study, using reciprocal crosses between normal-lifespan (NLS) and long-lifespan (LLS) lines, we investigated the transgenerational inheritance of paraquat-induced oxidative stress resistance across the parental, F₁, and F₂ generations, assessing survival, locomotor performance, and antioxidant biochemical defenses. The results showed that LLS flies had significantly higher resistance to paraquat than NLS flies, with females being more resistant than males. We also observed a sex-specific maternal effect on female survival, with N♂ × L♀ offspring having significantly lower mortality than L♂ × N♀ offspring in the F₁ and F₂ generations. Locomotor resilience was found to be the most robust transgenerational maternal effect (in both sexes and generations). Our narrow-sense heritability for negative geotaxis in males provided a measure of differential transgenerational transmission of locomotor resilience through mothers. Among the measured antioxidant defenses, glutathione was the most consistent transgenerational maternal antioxidant trait. N♂ × L♀ offspring had significantly higher glutathione levels than L♂ × N♀ in F₁ and F₂ generations in both sexes, with positive F₂ recombination values, indicating transgenerational amplification of glutathione-based antioxidant capacity. Catalase had near-zero heritability, consistent with its predominantly nuclear regulation. Variance partitioning analysis revealed prominent maternal contributions to ROS, LPO, SOD, and locomotion in the parental generation, which were reduced in subsequent generations. Taken together, these findings indicate that the adaptive stress resistance linked with longevity is heritable in Drosophila in a trait-dependent fashion, predominantly driven by the maternal lineage. Locomotion and glutathione regulation are the most maternally inherited traits, making them the primary subjects of subsequent studies on the cytoplasmic, epigenetic, and mitochondrial pathways that mediate transgenerational stress resistance.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191375","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":"Age-associated radiomic phenotyping in mice using multi-energy photon-counting and preclinical CT: an exploratory study.","authors":"Noah A Castioni, Carmen Wängler, Carolin Mogler, Björn Wängler, Caroline Cassia, Henning Rudolf, Matthias F Froelich, Stefan O Schoenberg, Alexander Hertel","doi":"10.1007/s10522-026-10524-y","DOIUrl":"10.1007/s10522-026-10524-y","url":null,"abstract":"<p><p>To investigate whether CT-derived radiomic features capture imaging patterns associated with chronological age groups in mice and to assess the influence of imaging platform and photon-counting CT reconstruction strategy on classification performance. Female C57BL/6NRj mice from three chronological age groups (28, 88, and 99 weeks; n = 11) underwent clinical photon-counting CT (PCCT) and preclinical Albira II CT. Heart, liver, and spleen were segmented and radiomic features were extracted. The individual mouse was defined as the independent biological unit. Model development and evaluation used nested leave-one-mouse-out cross-validation with all preprocessing, feature selection, model selection, and, where applicable, reconstruction-energy selection restricted to the respective training folds. Organ-level class probabilities were averaged to generate one mouse-level prediction. Monoenergetic PCCT reconstructions from 40 to 180 keV were evaluated, including a fully nested energy-and-pipeline selection analysis. A grouped mouse-level permutation analysis with 200 permutations was performed for the primary monoenergetic workflow. Albira II correctly classified 5/11 mice (45.5%; 95% CI, 21.3-72.0%), whereas PCCT-SPP correctly classified 10/11 mice (90.9%; 95% CI, 62.3-98.4%). The fully nested monoenergetic PCCT workflow correctly classified 9/11 mice (81.8%; 95% CI, 52.3-94.9%; balanced accuracy, 83.3%; macro-F1, 83.3%). Energy-specific performance varied considerably: 110 keV showed the highest accuracy (81.8%) and was selected in 7/11 outer folds, whereas the highest macro one-vs-rest AUC occurred at 130 keV (0.867). None of the 200 permuted analyses reached the observed fully nested monoenergetic accuracy (plus-one corrected Monte-Carlo p = 0.005). CT-derived radiomic features showed chronological age-group-associated patterns in this exploratory murine cohort, with classification performance varying substantially across imaging platforms and reconstruction strategies. PCCT-SPP showed the numerically highest performance, while monoenergetic PCCT demonstrated pronounced energy dependence without evidence for a universally optimal reconstruction energy. These findings require validation in larger independent cohorts and correlation with independent biological-aging reference measures.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191351","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":"Hippo-YAP/TAZ signalling at the crossroads of brain ageing and neurological disorders: mechanisms, crosstalk, and therapeutic prospects.","authors":"Bhaskar Jyoti Dutta, Vishal Shivaji Patil, Sanket Seksaria, Shradha Verma, Suman Basak","doi":"10.1007/s10522-026-10526-w","DOIUrl":"https://doi.org/10.1007/s10522-026-10526-w","url":null,"abstract":"<p><p>As life expectancy increases globally, ageing has emerged as the main risk factor driving the increasing burden of neurological disorders. Although advances have been made in understanding their pathogenesis, current therapies remain largely symptomatic and do not prevent disease progression. There is a growing body of evidence that these disorders share common molecular mechanisms, including oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy, ferroptosis, and blood-brain barrier disruption. Recently, the Hippo signalling pathway has been identified as a key regulator of these processes through its downstream effectors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). In addition to its well-characterised functions in the regulation of organ size and tissue regeneration, Hippo signalling has crucial roles in neuronal survival, maintenance of neural stem cells, synaptic plasticity, neurovascular integrity and cellular responses to metabolic and mechanical stress. Dysregulation of this pathway in aging contributes to cellular senescence, impaired tissue repair and progressive neurodegeneration. This review summarizes the physiological functions of Hippo-YAP/TAZ signaling in the aging brain and discusses its mechanistic involvement in major neurological disorders. We further highlight the extensive crosstalk between Hippo signalling and key pathways regulating inflammation, oxidative stress, autophagy, and mitochondrial homeostasis. Finally, recent advances in therapeutic strategies targeting Hippo signalling, including small-molecule modulators, drug-repurposing approaches, and natural bioactive compounds, are discussed along with current challenges and future perspectives. Collectively, the available evidence positions the Hippo-YAP/TAZ pathway as a promising therapeutic target for developing disease-modifying interventions against ageing-associated neurological disorders.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179275","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":"Geroprotective efficacy of Triphalaguggul: a polyherbal formulation against inflammatory disorders through inhibition of pro-inflammatory cytokines as therapeutic biomarkers.","authors":"Anumita Dey, Sriparna Datta, Mradu Gupta, Helen Chattapadhyay, Pranab Kumar Sahoo","doi":"10.1007/s10522-026-10519-9","DOIUrl":"https://doi.org/10.1007/s10522-026-10519-9","url":null,"abstract":"<p><p>Due to increase in life expectancy, aged population is growing exponentially, globally which has impact on human health as well as biomedical research. Research highlighted coordination between aging and arthritis where aging is the underlying hallmark of arthritis progression. Despite knowing the route of pathogenesis regarding most prevalent joint disorders like Osteoarthritis (OA) and rheumatoid arthritis (RA); efficient curable approach is still challenging. Worldwide 7-8% populations suffer from OA while 0.2-1% people are invaded by RA. Due to high cost, inadequate pharmacological action and adverse effects, NSAIDs are considered as secondary treatment option. Today, demographic changes towards polyherbal medicine usage targeting inhibition of pro-inflammatory cytokines are the challenge of the day. This study focused on Triphalaguggul (TG); a polyherbal formulation for treatment of arthritis targeting down regulation of pro-inflammatory cytokines and its signaling pathways. Toxicology study along with anti-OA and anti-RA evaluation in MIA and CFA induced rat model respectively. TG could reduce 96.15% inflamed knee, 95.18% paw edema and also helped in regrowth and rearrangement of chondrocytes properly in OA. In arthritic condition, increased hematological parameters like SGPT, SGOT, AlkP, CRP, RF were reinstated to normal range after treatment (p < 0.05). ELISA revealed that elevated IL-6, TNF-α, IL-1β were decreased after drug treatment (p < 0.05). Enhanced expression of p-JAK2, p-STAT3, NFκβ/p65 were downregulated (p < 0.05) after treatment which was validated by western blot and immunohistochemistry. Finding suggested that TG exhibited anti-arthritic activity down-regulating pro-inflammatory cytokines, JAK/STAT and NFƘβ signaling pathway as a therapeutic biomarker to protect from geriatric disease.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179263","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":"Interpreting ocular age estimates: source, output, evidence, and clinical meaning.","authors":"Henry Bair","doi":"10.1007/s10522-026-10525-x","DOIUrl":"https://doi.org/10.1007/s10522-026-10525-x","url":null,"abstract":"<p><p>Ocular age estimates derived from fundus photographs, optical coherence tomography, ocular fluids, systemic omics, and multimodal models are increasingly reported in years. The eye is unusually tractable for organ-specific aging research because it is paired, repeatedly imageable, locally treatable, and linked to quantitative function. The familiar scale can obscure differences in what was measured, what the model was developed to predict, which quantity is reported, and what the study design can support. Existing frameworks classify visual-aging biomarkers by biological domain and context of use. We propose an eye-specific framework organized around five declarations: proximal source; development target; reported quantity; evidence design; and intended use. Laterality, reference population, disease and treatment context, technical version, and uncertainty in the stated output remain essential annotations. A raw age gap is a cross-sectional residual, and an age-adjusted deviation requires calibration outside the outcome-analysis sample. Repeated application of a cross-sectional model does not establish an individual aging rate; longitudinal claims require repeated measurements against a longitudinal reference and change distinguishable from measurement variability. Visual-aging claims also need psychophysical, performance-based, or patient-reported validation. Differences across measurement domains must be assessed both against measurement error and against the distribution expected in the reference population. A persistent difference may support a candidate biological pattern only after technical and clinical explanations have been evaluated. Prognostic and clinical claims require separate prospective and decision-level evidence. These distinctions prevent a cross-sectional age residual from being mistaken for an aging rate, a prognostic marker, or a clinically actionable test.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164139","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":"ANGPTL8 induces the aging of hematopoietic stem/progenitor cells.","authors":"Meijuan Chen, Min Zhang, Hanyi Mei, Xinyu Bai, Xiaoli Wang, Yijun Tang, Hua Jiang, Lulu Zhang, Chunfang Zhou, Yahong Yuan","doi":"10.1007/s10522-026-10517-x","DOIUrl":"10.1007/s10522-026-10517-x","url":null,"abstract":"<p><p>Hematopoiesis depends on the sustained function of hematopoietic stem and progenitor cells (HSPCs). However, aging progressively impairs HSPC function, contributing to immunosenescence, hematologic malignancies, and degenerative disorders. Therefore, elucidating the mechanisms underlying HSPC aging is essential for developing strategies to alleviate age-related dysfunction. Here, we identify angiopoietin-like 8 (ANGPTL8), a secreted glycoprotein known for its role in glucose and lipid metabolism, as a novel regulator of HSPC aging. Systemic ANGPTL8 knockout significantly attenuated senescence-associated phenotypes in multiple murine tissues. In vitro and in vivo analyses of proliferation, colony-forming capacity, mitochondrial membrane potential, senescence-associated secretory phenotype (SASP) expression, reactive oxygen species (ROS) accumulation, myeloid skewing, and early hematopoietic regeneration further demonstrated that ANGPTL8 promotes HSPC aging. Mechanistically, ANGPTL8 deficiency activated the PI3K/AKT signaling pathway, whereas a PI3K activator rescued the senescence effects induced by recombinant ANGPTL8 (rANGPTL8). Furthermore, co-immunoprecipitation (Co-IP) confirmed that rANGPTL8 directly interacts with the transmembrane receptor PirB. Recombinant PirB (rPirB) reduced the phosphorylation of PI3K/AKT, whereas PirB knockdown effectively blocked the inhibitory effect of rANGPTL8 on PI3K/AKT phosphorylation. Collectively, our findings suggest that ANGPTL8 drives HSPC aging primarily by suppressing the PI3K/AKT pathway via its receptor PirB, providing a new potential target to alleviate the aging of HSPCs.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134495","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":"An integrated resource for systems-level analysis of aging hallmarks and associated genes.","authors":"Rahul Tiwari, Mridhula Balaji, Nikhil Chivukula, Priyotosh Sil, Areejit Samal","doi":"10.1007/s10522-026-10520-2","DOIUrl":"https://doi.org/10.1007/s10522-026-10520-2","url":null,"abstract":"<p><p>AgingHallmarksDB is an interactive web platform designed to facilitate systems-level aging research centered on 11 aging hallmarks. It comprises 3111 aging hallmark-associated genes integrated from seven established databases, including a high-confidence consensus set comprising 1089 genes. It further incorporates tissue, cell-type class, exosomes, protein-protein and regulatory interactions to facilitate deeper biological insights. AgingHallmarksDB enables over representation analysis (ORA) and gene set enrichment analysis (GSEA) to elucidate varying molecular mechanisms underlying aging. Gene overlaps and Jaccard similarity revealed interconnectedness among the hallmarks. Network analyses further showed these pairs are connected within the protein-protein interaction (PPI) network. The utility of this resource was demonstrated through multiple hallmark-associated analyses. PPI network topology analysis of common hallmark genes revealed several key age-associated genes that act as central hubs across multiple aging hallmarks. Hallmark enrichment analyses revealed extensive coverage across aging-related diseases compared to limited enrichment seen in non-aging-related diseases like developmental and congenital diseases. Further these analyses showed biologically meaningful disease-associated processes, like \"Loss of proteostasis\" in Alzheimer's disease and \"Chronic inflammation\" in atherosclerosis as highly significant hallmarks. These disease-hallmark associations were further supported by network proximity analyses. In addition, GSEA of the PM2.5 exposure-associated skin transcriptome identified significant enrichment of aging hallmarks, particularly \"Epigenetic alterations\", demonstrating the resource's utility in interpreting transcriptomic datasets within the context of aging biology. Overall, AgingHallmarksDB provides a robust framework for investigating hallmark-associated functionality, and potential therapeutic discovery in aging and longevity. AgingHallmarksDB is accessible at https://cb.imsc.res.in/aginghallmarksdb/ .</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126668","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}