Mechanisms of Ageing and Development最新文献

{"title":"Aging of the Colon – A Mechanistic View","authors":"Christopher Hofmann ,&nbsp;Hartmut Geiger","doi":"10.1016/j.mad.2025.112143","DOIUrl":"10.1016/j.mad.2025.112143","url":null,"abstract":"<div><div>The colon is one of the gastrointestinal organs most profoundly affected by aging. Recent advances in our understanding of both colonic physiology and the general mechanisms of aging have significantly expanded our knowledge of the types and underlying processes of colonic aging. In this review, we summarize current insights into the cellular and molecular mechanisms that drive physiological aging of the human colon. We examine the unique structural and functional features of key components of the colon, including the epithelium, local immune system, microbiome, enteric neurons, and smooth muscle cells, and explore how aging affects each of these cell populations, ultimately impacting overall colonic function. In the epithelium, increased mutational burden does not appear to be the primary driver of age-related dysfunction. Instead, dysregulation of signaling pathways such as EGF and Wnt is likely responsible for key phenotypic changes. Aged colonic neurons display protein misfolding and axonal dysfunction reminiscent of aging processes observed in the central nervous system. Similarly, smooth muscle cells exhibit impaired contractility, which is associated with disruptions in calcium homeostasis and deficits in cholinergic signaling. At the same time, age-related activation of the local immune system mirrors broader immunosenescence and may be further influenced by shifts in the gut microbiome, although a consistent aging-associated microbiome signature has yet to be identified. These multifaceted changes, combined with the colon’s inherent regional and cellular complexity and the challenges of modeling human colonic aging, continue to fascinate but also pose substantial obstacles for research. Emerging experimental models and clinical strategies offer promising avenues for improving the prevention and treatment of age-associated colonic dysfunction.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112143"},"PeriodicalIF":5.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compatibility and comparative analysis of chronological and biological aging between the legacy 450K and the EPIC v2.0 arrays","authors":"Sven De Pourcq ,&nbsp;Pei-Lun Kuo ,&nbsp;Ann Zenobia Moore ,&nbsp;Stefania Bandinelli ,&nbsp;Steve Horvath ,&nbsp;Luigi Ferrucci ,&nbsp;Valeria Santini","doi":"10.1016/j.mad.2025.112142","DOIUrl":"10.1016/j.mad.2025.112142","url":null,"abstract":"<div><div>Several epigenetic clocks based on DNA methylation arrays have been developed to evaluate biological aging. However, there is limited information on how the newer EPIC v2.0 arrays affect clock estimations, which lack probes initially present on legacy arrays such as the 450K array. Therefore, we analyzed how this absence affects epigenetic clock estimates using data from the InCHIANTI study. Although some clocks showed significant over- or underestimation due to probe loss, correlations between estimates from all 450K probes (unreduced) and shared probes between 450K and EPIC v2.0 (reduced) remained significant. AgeAcceleration estimates were least affected by missing probes.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112142"},"PeriodicalIF":5.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHT ameliorates cardiac aging in progeroid mice by XRCC4-mediated genome stabilization","authors":"Rui Jiang ,&nbsp;Hao Wang ,&nbsp;Weina Zhang ,&nbsp;Jiaxi Li ,&nbsp;Shiqi Huang ,&nbsp;Lingjiang Chen ,&nbsp;Yuhan Min ,&nbsp;Zhaohui Ouyang ,&nbsp;Ying Jiang ,&nbsp;Zhiyong Mao ,&nbsp;Guizhu Wu ,&nbsp;Ke Wei ,&nbsp;Yu Chen","doi":"10.1016/j.mad.2025.112141","DOIUrl":"10.1016/j.mad.2025.112141","url":null,"abstract":"<div><div>Cardiovascular compromise is the primary cause of death in Hutchinson-Gilford Progeria Syndrome (HGPS), a lethal segmental premature aging disorder; however, no therapies directly target its underlying cardiac pathology. Our prior work established that non-homologous end joining (NHEJ)—the dominant pathway for double-strand break repair and genomic stabilization in cardiomyocytes—is impaired in HGPS mice, triggering cardiac atrophy via a CHK2-AMPKα-FOXO3A signaling axis. While forced cardiac hypertrophy can ameliorate pathology, whether restoring DNA repair capacity constitutes a viable therapeutic strategy remains unknown. Here, utilizing dihydrotestosterone (DHT), we demonstrate that NHEJ activation stabilizes the cardiomyocyte genome, increases cardiomyocyte size, and enhances contractile function. Furthermore, DHT administration reduces DNA damage accumulation and promotes structural and functional recovery in HGPS hearts. Transcriptome analysis further demonstrates that DHT treatment rejuvenates HGPS hearts, upregulates pathways linked to heart function and downregulates inflammatory responses, a key driver of cardiac aging and disease. Collectively, our findings support NHEJ activation as a promising therapeutic approach for mitigating HGPS-associated cardiac degeneration and ameliorating cardiac aging.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112141"},"PeriodicalIF":5.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ashwagandha withanolides, Withaferin-A, and Withanone for natural interventions in aging and obesity","authors":"Ren Yoshitomi ,&nbsp;Rajeswari Nanda ,&nbsp;Kazumi Hirano ,&nbsp;Sunil C. Kaul ,&nbsp;Jaspreet Kaur Dhanjal ,&nbsp;Renu Wadhwa","doi":"10.1016/j.mad.2025.112126","DOIUrl":"10.1016/j.mad.2025.112126","url":null,"abstract":"<div><div>Aging and obesity are closely connected, with obesity being a major risk factor for many age-related diseases caused by chronic inflammation and mobility problems. Lifestyle choices such as good nutrition, including medicinal herbs, and exercise are believed to influence body weight. Ashwagandha, an Ayurvedic adaptogen containing bioactive withanolides, is known to reduce stress, fight cancer, and improve energy metabolism. Its effects on lipid metabolism and obesity remain unclear. CARF (Collaborator of ARF), a protein involved in stress response and cancer regulation, was recently found to control liver lipid metabolism. We used a hepatocyte-based screening assay in which induction of fatty acid accumulation caused downregulation of CARF. On the other hand, cells treated with Ashwagandha withanolides showed CARF recovery and reduction in lipid accumulation. Molecular analyses on key regulators of stress and lipogenesis pathways supported antioxidative and antisteatotic effects of Withaferin-A (Wi-A) and Withanone (Wi-N). We discuss various antiaging activities of Ashwagandha withanolides and report computational molecular modeling-based insights into the interactions of Wi-A and Wi-N with three key targets (Fatty Acid Synthase, FASN; Sterol Regulatory Element-Binding protein-1c, SREBP-1c; and Peroxisome Proliferator-Activated Receptor, PPARγ) of the lipogenesis pathway, highlighting their potential in regulating lipid metabolism and obesity.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112126"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of concern: Regulation of β-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease.","authors":"R P Jaya Prasanthi, Eric Schommer, Sarah Thomasson, Alex Thompson, Gwen Feist, Othman Ghribi","doi":"10.1016/j.mad.2025.112121","DOIUrl":"https://doi.org/10.1016/j.mad.2025.112121","url":null,"abstract":"","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"112121"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cGAS-STING signaling is blunted in senescent macrophages and monocytes in obesity","authors":"Carine Raquel Richter Schmitz ,&nbsp;Lucas Kich Grun ,&nbsp;Bruno Kendi Makiyama ,&nbsp;Luma Smidt Piazza ,&nbsp;Alexandre Vontobel Padoin ,&nbsp;Cláudio Cora Mottin ,&nbsp;Moisés Evandro Bauer ,&nbsp;Fátima Theresinha Costa Rodrigues Guma ,&nbsp;Florencia María Barbé-Tuana","doi":"10.1016/j.mad.2025.112140","DOIUrl":"10.1016/j.mad.2025.112140","url":null,"abstract":"<div><h3>Introduction</h3><div>The cGAS-STING pathway is essential for immunity, detecting cytosolic DNA to trigger defense mechanisms and sterile inflammation linked to aging, obesity, and chronic inflammatory diseases. This study examines cGAS-STING signaling in senescent monocyte-derived macrophages (MDMs) and monocytes within the context of obesity.</div></div><div><h3>Materials and Methods</h3><div>Primary human MDMs were differentiated from peripheral blood of young, healthy, lean donors using M-CSF, to guide monocytes toward the macrophage lineage. MDMs were cultured for 7 or 21 days to induce replicative senescence. Peripheral monocytes were also isolated from age- and sex-matched lean and obese participants.</div></div><div><h3>Results</h3><div>MDMs cultured for 21 days exhibited increased cellular and nuclear area, developed a senescent phenotype marked by increased P16 expression and γH2AX phosphorylation, shorter telomeres, loss of LAMIN B1, diminished phagocytosis, with reduced STING expression and impaired response to cGAS agonist 2′3'-cGAMP. Similarly, <em>ex vivo</em> monocytes from individuals with obesity displayed elevated P16 expression and increased γH2AX and β-galactosidase activity, along with increased STING expression, compromised downstream signaling and reduced cytokine secretion.</div></div><div><h3>Discussion</h3><div>Dysfunctional cGAS-STING signaling and senescence markers suggest a shared mechanism underlying immune dysfunction in aging and obesity. Understanding cGAS-STING’s role in immune cells may provide insights into age-related immune decline and chronic inflammation.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112140"},"PeriodicalIF":5.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The TGF-β1-oxidative stress axis underlies accelerated senescence of endothelial cells exposed to serum from hypertensive patients","authors":"Paweł Uruski ,&nbsp;Justyna Mikuła-Pietrasik ,&nbsp;Andrzej Tykarski ,&nbsp;Krzysztof Książek","doi":"10.1016/j.mad.2025.112128","DOIUrl":"10.1016/j.mad.2025.112128","url":null,"abstract":"<div><h3>Background</h3><div>There is a bidirectional link between hypertension (HT) and cellular senescence of endothelial cells (ECs). However, the mechanisms underlying EC senescence in patients with HT are not yet fully understood.</div></div><div><h3>Methods and Results</h3><div>We analyzed serum from 71 patients with primary HT and compared it to serum from 25 healthy donors to assess its effects on EC biology, including biomarkers, signaling pathways, and cellular senescence effectors. Our findings revealed that exposing ECs to serum from HT patients (20 % for 72 h) impaired cell viability while enhancing proliferation, migration, and tubulogenesis. This effect is accompanied by increased expression of HIF-1α. Additionally, HT serum potentiated the expression of the senescence marker SA-β-Gal, shortened telomeres, and up-regulated cell-cycle inhibitors p16, p21, and p53. Regarding the signaling pathways, HT serum activated ERK1/2, p38 MAPK, AP-1/c-jun, and Notch1. Indices of oxidative stress in ECs treated with HT serum also increased, as indicated by elevated production of superoxides, activation of antioxidants (SOD, CAT), and accumulation of oxidized DNA, proteins, and lipids. Furthermore, mitochondria in these cells displayed decreased inner membrane potential and increased biogenesis, likely due to enhanced activity of PGC-1α. The activity of respiratory chain enzymes, including cytochrome c oxidase and NADH dehydrogenase, was also elevated. When HT serum-treated ECs were pre-incubated with the ROS scavenger PBN, the activity of SA-β-Gal decreased. A similar reduction in SA-β-Gal activity was observed when HT serum, which contained elevated levels of TGF-β1, was pre-incubated with a TGF-β1-neutralizing antibody. Importantly, exogenous TGF-β1, administered at a dose corresponding to its concentration in HT serum, induced senescence in ECs.</div></div><div><h3>Conclusions</h3><div>Our results indicate that serum from HT patients promotes senescence in ECs through mechanisms related to TGF-β1 and oxidative stress signaling.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112128"},"PeriodicalIF":5.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between metabolic profile and cognitive frailty in community-dwelling older adults: An eight-year cohort study","authors":"Te-Hsuan Huang ,&nbsp;Yen-Ching Chen ,&nbsp;Ching-Yu Lin ,&nbsp;Yu-Ting Wang ,&nbsp;Pei-Yu Wang ,&nbsp;Jeng-Min Chiou ,&nbsp;Jen-Hau Chen","doi":"10.1016/j.mad.2025.112130","DOIUrl":"10.1016/j.mad.2025.112130","url":null,"abstract":"<div><div>Limited studies have explored the link between metabolic profiles and cognitive frailty, its temporal relationship is especially lacking. This study aimed to identify metabolic patterns associated with cognitive frailty over time. This eight-year prospective cohort study (2011–2019) recruited 605 nondemented community-dwelling older adults at baseline. Cognitive frailty, assessed biennially, was defined as physical frailty and mild cognitive impairment. Baseline plasma metabolites were evaluated using ¹H nuclear magnetic resonance. Generalized linear mixed models assessed the longitudinal association between metabolites and cognitive frailty, further stratified by important covariates. We found that one unit increment of baseline fatty acyl chain (CH₂CH₂C<img>C) Z-score was associated with worsening cognitive frailty at baseline [adjusted risk ratio (aRR)= 1.97], which attenuated over eight years (aRR=0.94). In contrast, one unit increment of baseline pyruvate Z-score was associated with attenuation in the progression to the next stage of cognitive frailty (aRR=0.94). These associations were more evident in men, individuals with &gt; 12 years of education, and apolipoprotein E (<em>APOE</em>) ε4 non-carriers (aRR=0.34–0.92). Significant interactions were found between <em>APOE</em> ε4 status and both fatty acyl chain (<em>P</em>_{<em>interaction</em>}=0.004) and pyruvate (<em>P</em>_{<em>interaction</em>}=0.03). Our findings suggest plasma metabolites may serve as markers for predicting cognitive frailty and <em>APOE</em> genotypes modifying this pathogenesis.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112130"},"PeriodicalIF":5.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causes and consequences of chromosomal cohesin loss: Novel insights for mechanisms of aging-related oocyte aneuploidy","authors":"Lu‑lu Fu ,&nbsp;Jing‑shun Zhang ,&nbsp;Xue‑ying Zhang ,&nbsp;Ying Xu ,&nbsp;Fu-liang Zhang ,&nbsp;Lian‑wen Zheng","doi":"10.1016/j.mad.2025.112129","DOIUrl":"10.1016/j.mad.2025.112129","url":null,"abstract":"<div><div>Female fertility sharply declines from the mid-thirties of their life, mainly due to age-related decreases in oocyte quality and quantity. Among numerous interconnected maternal factors, an increase in the incidence of aneuploidy caused by meiotic errors is a leading cause of oocyte competence decrease. Why advanced maternal age increases the likelihood of chromosome segregation errors in oocytes remains one of the outstanding questions in reproductive and developmental biology, and it is becoming more important as the age at which women have children continues to rise. A better understanding of this question is crucial for developing effective strategies for prophylaxis or therapeutic interventions for infertility. The progressive loss of cohesin, a ring-shaped protein complex with fundamental roles in chromosome cohesion and architecture, has recently been heavily implicated in the increase in oocyte aneuploidy rates during maternal aging. This review discusses the underlying mechanisms of age-related aneuploidy in oocytes. We particularly ask how chromosomal cohesin loss affects the fidelity of oocyte chromosome segregation and examine physiological factors that contribute to this deterioration.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112129"},"PeriodicalIF":5.1,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic stroke and comorbidities: Impact on recovery and the role of genetics and epigenetics","authors":"Andreea Cercel ,&nbsp;Abuzan Mihaela ,&nbsp;Thorsten R. Doeppner ,&nbsp;Dirk M. Hermann ,&nbsp;Liviu Martin ,&nbsp;Aurel Popa-Wagner","doi":"10.1016/j.mad.2025.112127","DOIUrl":"10.1016/j.mad.2025.112127","url":null,"abstract":"<div><div>Ischemic stroke (IS) remains a leading cause of long-term disability and mortality worldwide, with recovery outcomes shaped by the interplay between acute vascular injury, pre-existing comorbidities, and individual molecular profiles. Common risk factors—such as diabetes mellitus, atrial fibrillation, hypertension, and dyslipidemia—not only increase stroke susceptibility but also impair neurovascular repair by perpetuating systemic inflammation, endothelial dysfunction, and impaired neuroplasticity. Aging remains an underexplored determinant of epigenetic remodeling in stroke. Beyond these clinical determinants, genetic and epigenetic mechanisms contribute substantially to stroke heterogeneity. Genome-wide association studies (GWAS) have identified loci such as HDAC9, PATJ, PTCH1, and ABO that modulate inflammation, oxidative stress, and vascular remodeling. Complementary epigenetic pathways, including DNA methylation, histone acetylation, and circular RNAs (circRNAs), dynamically regulate gene expression in response to ischemia and comorbid influences, encoding a persistent “molecular memory” that shapes both injury and repair. Functional studies reveal that circRNAs orchestrate apoptosis, angiogenesis, and synaptic remodeling, while selective DNMT and HDAC inhibition can restore neurovascular integrity in experimental models. Recent multi-omics and longitudinal approaches demonstrate that these molecular signatures evolve across acute, subacute, and chronic phases of recovery, yet clinical translation remains limited. Aging and chronic comorbidities further modify epigenetic programs, reducing repair capacity. Although genotype-guided antiplatelet therapy illustrates the feasibility of personalized stroke care, broader genomics- and epigenetics-informed interventions require rigorous validation. This review integrates current knowledge on the interplay between vascular comorbidities, genetic predisposition, and epigenetic regulation in shaping stroke recovery. Understanding these interactions is essential for developing precision medicine approaches that enhance functional outcomes and reduce recurrence in stroke survivors.Integrating multi-omics profiling with comorbidity stratification, functional validation, and longitudinal biomarker tracking will be pivotal to achieving actionable precision medicine and improving outcomes in stroke survivors.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112127"},"PeriodicalIF":5.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}