A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement

Life Medicine, Год журнала: 2024, Номер 3(1)

Опубликована: Янв. 29, 2024

In human aging, liver aging per se not only increases susceptibility to diseases but also vulnerability of other organs given its central role in regulating metabolism. Total function tends be well maintained the healthy elderly, so is generally difficult identify early. response this critical challenge, Aging Biomarker Consortium China has formulated an expert consensus on biomarkers by synthesizing latest scientific literature, comprising insights from both scientists and clinicians. This provides a comprehensive assessment associated with presents systematic framework characterize these into three dimensions: functional, imaging, humoral. For functional domain, we highlight cholesterol metabolism liver-related coagulation function. imaging note that hepatic steatosis blood flow can serve as measurable for aging. Finally, humoral pinpoint hepatokines enzymatic alterations worthy attention. The aim establish foundation assessing extent early signs aging-related diseases, thereby improving health life expectancy elderly population.

Язык: Английский

---

Role of pattern recognition receptors in the development of MASLD and potential therapeutic applications

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116724 - 116724

Опубликована: Май 17, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent diseases worldwide, and its occurrence is strongly associated with obesity, insulin resistance (IR), genetics, metabolic stress. Ranging from simple fatty to steatohepatitis (MASH), even severe complications such as fibrosis advanced cirrhosis or hepatocellular carcinoma, underlying mechanisms MASLD progression are complex involve multiple cellular mediators related signaling pathways. Pattern recognition receptors (PRRs) innate immune system, including Toll-like (TLRs), C-type lectin (CLRs), NOD-like (NLRs), RIG-like (RLRs), DNA receptors, have been demonstrated potentially contribute pathogenesis for MASLD. Their pathways can induce inflammation, mediate oxidative stress, affect gut microbiota balance, ultimately resulting in hepatic steatosis, inflammatory injury fibrosis. Here we review available literature regarding involvement PRR-associated signals pathogenic clinical features MASLD, vitro animal models We also discuss emerging targets PRRs drug developments that involved agent therapies intended arrest reverse progression, thus enabling refinement therapeutic accelerate development.

Язык: Английский

---

Single-cell transcriptomics reveals the impact of sex and age in the healthy human liver

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract The liver is a vital organ composed of parenchymal, nonparenchymal, and immune cell populations, which are now being mapped at single resolution. Here we present detailed map the cellular composition human through single-nucleus RNA sequencing (snRNA-seq), incorporating insights from 32 healthy samples. dataset contains cells female male donors spanning more than seven decades age. Excluding X Y chromosome, identified ∼500 genes uniquely enriched in liver, ∼600 liver. These tend to be across multiple types females restricted individual males. define unique circuitries within each type between males their impact on cell-cell communication response external signals, including enrichment cholesterol/lipid metabolism associated angiopoietin-like protein (ANGPTL) signaling bone morphogenic (BMP) cells. With increased age, observe greater diversity gene expression, that regulate neuregulin (NGR) signaling. While fewer younger regulating insulin growth factor (IGF) this group. Together, these results activities sex age provide reference for future comparisons different ancestries, geographies, disease states. One Sentence Summary We applied features influenced by subtypes

Язык: Английский

---

A single-cell network approach to decode metabolic regulation in gynecologic and breast cancers

npj Systems Biology and Applications, Год журнала: 2025, Номер 11(1)

Опубликована: Март 13, 2025

Cancer metabolism is characterized by significant heterogeneity, presenting challenges for treatment efficacy and patient outcomes. Understanding this heterogeneity its regulatory mechanisms at single-cell resolution crucial developing personalized therapeutic strategies. In study, we employed a network approach to characterize malignant in gynecologic breast cancers, focusing on the transcriptional driving metabolic alterations. By leveraging RNA sequencing (scRNA-seq) data, assessed pathway activities inferred cancer-specific protein-protein interactomes (PPI) gene networks (GRNs). We explored crosstalk between these identify key alterations regulation. Clustering cells pathways revealed tumor across highlighting variations oxidative phosphorylation, glycolysis, cholesterol, fatty acid, hormone, amino redox metabolism. Our analysis identified modules associated with pathways, along their regulators. These findings provide insights into complex interplay rewiring regulation paving way potential targeted strategies precision oncology. Furthermore, pipeline dissecting coregulatory can be broadly applied decipher any disease resolution.

Язык: Английский

---

The role of NLRP12 in inflammatory diseases

European Journal of Pharmacology, Год журнала: 2023, Номер 956, С. 175995 - 175995

Опубликована: Авг. 11, 2023

Nucleotide-binding leucine-rich repeat-containing receptor 12 (NLRP12), a highly conserved protein containing an N-terminal pyrin domain (PYD), nucleotide-binding and C-terminal repeat region, belongs to the oligomerization domain-like receptor-containing PYD (NLRP) family is cytoplasmic sensor that plays negative role in inflammation. NLRP12 involved multiple disease processes, including formation of inflammasomes regulation both canonical noncanonical inflammatory signaling pathways. pathogenic infections are closely linked, alterations expression activity associated with diseases. In this review, we begin summary mechanisms by NLRP12. We then underscore important roles onset progression inflammation, infectious disease, host defense, carcinogenesis COVID-19. Finally, highlight factors influence activity, synthetic naturally derived agonists, regarded as potential therapeutic agents overcome

Язык: Английский

---

Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat

Journal of Cellular and Molecular Medicine, Год журнала: 2023, Номер 28(1)

Опубликована: Окт. 28, 2023

Abstract This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30‐day intermittent fasting (IF) program in 24‐month‐old male Sprague–Dawley rats. Rats underwent 18‐h daily received 1 × 10 8 CFU daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, SVM techniques, while histopathological evaluations used Haematoxylin eosin Masson trichrome‐stained tissues. Blood samples collected for biochemical analysis. Gross alterations quantity observed with individual or combined treatments. LDA analyses demonstrated high accuracy differentiating control treated groups. The combination treatments led most significant reduction cholesterol ester (1740 cm −1 ) improved protein phosphorylation (A 1239 /A 2955 A 1080 1545 carbonylation 1740 ). Individually, IF more effective enhancing membrane dynamics (Bw 2922 /Bw In groups, showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis fibrosis. Serum ALP, LDH albumin levels significantly increased treatment offers valuable insights into potential mechanisms behind beneficial effects content, contributing development personalized nutrition health strategies.

Язык: Английский

---

Investigating Mitochondrial Gene Expression Patterns in Drosophila melanogaster Using Network Analysis to Understand Aging Mechanisms

Applied Sciences, Год журнала: 2023, Номер 13(12), С. 7342 - 7342

Опубликована: Июнь 20, 2023

The process of aging is a complex phenomenon that involves progressive decline in physiological functions required for survival and fertility. To better understand the mechanisms underlying this process, scientific community has utilized several tools. Among them, mitochondrial DNA emerged as crucial factor biological aging, given dysfunction thought to significantly contribute phenomenon. Additionally, Drosophila melanogaster proven be valuable model organism studying due its low cost, capacity generate large populations, ease genetic manipulation tissue dissection. Moreover, graph theory been employed dynamic changes gene expression patterns associated with investigate interactions between aging-related diseases. In study, we have integrated these approaches examine co-expression at various stages development. By applying graph-theory techniques, identified modules co-expressing genes, highlighting those contain high number genes. We found important genes involved age-related diseases melanogaster, including UQCR-C1, ND-B17.2, ND-20, Pdhb. Our findings shed light on role demonstrate utility research.

Язык: Английский

---

Arginine metabolism is a biomarker of red blood cell and human aging

Aging Cell, Год журнала: 2024, Номер unknown

Опубликована: Окт. 30, 2024

Abstract Increasing global life expectancy motivates investigations of molecular mechanisms aging and age‐related diseases. This study examines age‐associated changes in red blood cells (RBCs), the most numerous host cell humans. Four cohorts, including healthy individuals patients with sickle disease, were analyzed to define age‐dependent RBC metabolism. Over 15,700 specimens from 13,757 humans examined, a major expansion over previous studies RBCs aging. Multi‐omics approaches identified chronological alterations arginine pathway increased utilization older individuals. These consistent across disease cohorts influenced by genetic variation, sex, body mass index. Integrating multi‐omics data metabolite quantitative trait loci (mQTL) 525 diversity outbred mice functionally linked metabolism during storage vesiculation—a hallmark aging—and lower post‐transfusion hemoglobin increments. Thus, is biomarker organismal aging, suggesting potential new targets for addressing sequelae

Язык: Английский

---

Non-Alcoholic Fatty Liver Disease Diagnosis with Multi-Group Factors

Studies in health technology and informatics, Год журнала: 2023, Номер unknown

Опубликована: Июнь 29, 2023

Although various clinical factors affect the diagnosis of Non-alcoholic Fatty Liver Disease (NAFLD), most studies only use single-source data such as images or laboratory data. Nevertheless, using different categories features can help to get better results. Hence, one important purposes this paper is employ a multi-group effective velocimetry, psychological, demographic and anthropometric, lab test Then, some Machine Learning (ML) methods are applied classify samples into two healthy patient with NAFLD groups. The used here belongs PERSIAN Organizational Cohort study at Mashhad University Medical Sciences. To quantify scalability models, validity metrics used. obtained results illustrate that proposed method lead an increase in efficiency classifiers.

Язык: Английский

---

A physically inspired approach to coarse-graining transcriptomes reveals the dynamics of aging

PLoS ONE, Год журнала: 2024, Номер 19(10), С. e0301159 - e0301159

Опубликована: Окт. 29, 2024

Single-cell RNA sequencing has enabled the study of aging at a molecular scale. While substantial progress been made in measuring age-related gene expression, underlying patterns and mechanisms transcriptomes remain poorly understood. To address this gap, we propose physics-inspired, data-analysis approach to extract additional insights from single-cell data. By considering genome as many-body interacting system, leverage central idea Renormalization Group construct an hierarchically describe across spectrum scales for expresion. This framework provides quantitative language multiscale transcriptomes. Overall, our demonstrates value leveraging theoretical physics concepts like gain new biological complex high-dimensional

Язык: Английский

---