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The gut microbiota-metabolome axis mediates the adaptive protective effects of a high-altitude probiotic against distinct aging etiologies.

Aging is a major driver of chronic diseases and mortality, yet effective interventions against distinct aging etiologies remain limited. Hyp … tenuated, with lower interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) concentrations. Cellular senescence, assessed using senescence-associated β-galactosidase (SA-β-gal) and p16 immunofluorescence, was markedly reduced in both liver and colon tissues by approximately 50-60%. The probiotic rebalanced the gut microbiota composition by consistently suppre …

Потеря NOR1 связана с воспалением и биологическим старением в коре склероза.

Кортикальное нейродегенерирование и глиальная активация являются основными движущими силами развития инвалидности при множественном склерозе, однако молекулярные механизмы, лежащие в основе этих процессов, по-прежнему плохо определены. Членами семейства ядерных рецепторов NR4A являются реагирующие на стресс факторы транскрипции, которые регулируют нейронное выживание, воспалительную сигнализацию и клеточную адаптацию к метаболическому и окислительному стрессу. В частности, сиротский рецептор нейронного происхождения 1 (NR4A3) был замешан в нейрозащитных и реадаптивных реакциях на стресс в друг

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… Acta Neurol Scand . 2006 ; 113 : 48 – 50 . 10.1111/j.1600-0404.2006.00615.x 16637929 8 Papadopoulos D , Magliozzi R , Bandiera S , et al Accelerated cellular senescence in progressive multiple sclerosis: A histopathological study . … Nat Aging . 2021 ; 1 ( 12 ): 1107 – 1116 . 35531351 10.1038/s43587-021-00142-3 PMC9075501 47 Sikora E , Bielak-Zmijewska A , Dudkowska M , et al Cellular senescence in brain aging . …

Synergistic Effect of Banaba Leaf Extract and Policosanol (Raydel®) Ameliorate High Cholesterol and High Galactose-Diet Induced Adverse Events in Zebrafish.

Background: This study aimed to explore the therapeutic potential of a dietary regimen of banaba leaf extract (BNB), policosanol (PCO, Rayde … a profound impact on mitigating HC+HG elevated reactive oxygen species (ROS) generation, apoptosis, cellular senescence, and accumulation of brain-binding lipid proteins (BLBPs) and 4-hydroxynoneal (4-HNE) in the brain. Conclusions: The findings highlight the synergistic effects of the BNB and PCO combination to mitigate the adversity posed by the consumption of the …

Therapeutic effects of Total flavonoids of Epimedium Folium on sarcopenia via modulation of gut microbiota and bile acid metabolism.

BACKGROUND: The total flavonoids of Epimedii Folium (Epimedium brevicornu Maxim.) are the main active component, and have unique advantages in sarcopenia intervention. Nevertheless, its efficacy and mechanism of action have not been reported in the literature. AIM OF THE STUDY: This study aimed to evaluate the impact of TFE on sarcopenia and to elucidate the mechanisms involving the FXR-FGF15 signaling pathway and the gut microbiota-bile acid-skeletal muscle axis. METHODS: At the cellular level, the effects of TFE on C2C12 myotube morphology, as well as on myogenic growth factors and atrophy

An Overview of Current Research on Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Bibliometric Analysis From 2009 to 2021.

Background: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are important mediators of intercellular communication and participate in numerous physiological and pathological processes in the body. This study aims to introduce the research status, analyze the research hotspots, and predict the development trend through bibliometric analysis of MSC-EVs. Methods: We searched all relevant literature on MSC-EVs from 2009 to 2021 in the Web of Science. R-bibliometrix, VOSviewer, and CiteSpace software were used to visualize the quantitative analysis of the published literature, includ

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… From gonogenesis, embryogenesis to age-related cellular senescence, EVs are involved in almost the entire life cycle of human beings ( Machtinger et al., 2016 ; Takasugi, 2018 ). … BMSCs-derived EVs from young mice were able to reduce cellular senescence, improve stem cell function and extend the life span of mice ( Dorronsoro et al., 2021 ). …

Single-cell and spatial transcriptome analysis reveals the potential therapeutic targets for testicular sex cord-stromal cell tumor.

Testicular sex cord stromal tumor (TSCST) is a rare testicular tumor with unknown molecular mechanisms, tumor microenvironment (TME) and limited therapeutic options. To define the molecular mechanism and potential targets of TSCST, we combined single-cell RNA sequencing with single-cell nuclear RNA sequencing along with spatial transcriptomics from different TSCST tumor regions. This revealed significantly low expression of immune cell genes in tumor areas, indicating an immune-cold tumor environment and a critical epithelial-mesenchymal transition program during tumorigenesis and disease prog

Accelerated Aging in Cancer and Cancer Treatment: Current Status of Biomarkers.

BackgroundAging in humans is a heterogeneous process influenced by both biological and chronological factors. Biological age reflects an ind … ummarizes the current literature on aging biomarkers in cancer patients, with a focus on markers of cellular senescence and epigenetic modification. We evaluate the existing evidence supporting their use as predictors of toxicity in patients undergoing chemotherapy and radiation therapy.ResultsBiomarkers such as interleukin-6 (IL-6), leukocyte telomere length (LTL), …

Molecular and phenotypic blueprint of human hematopoiesis links proliferation stress to stem cell aging.

Hematopoietic stem/progenitor cells (HSPC) aging has long been associated with myeloid skewing, reduced clonal output, and impaired regenerative capacity, but quantitative immunophenotypic and functional analysis across the human lifespan has been lacking. Here, we provide a comprehensive phenotypic, transcriptional, and functional dissection of human hematopoiesis from youth to advanced age. Although primitive hematopoietic stem cell (HSC) numbers were stable during aging, overall cellularity declined, especially for erythroid and lymphoid lineages. HSPCs from older individuals exhibited repo

Central role for cholangiocyte pathobiology in cholestatic liver diseases.

Cholangiopathies comprise a spectrum of chronic intrahepatic and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis, and often cirrhosis and its sequela. Treatment for these diseases is limited, and collectively, they are one of the therapeutic "black boxes" in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators but also common cellular and molecular events driving disease progression (eg, cholestatic fibrogenesis, inflammation, and duct damage). The common pathways involve cholangiocytes,

Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations.

Telomere shortening can result in cellular senescence and in increased level of genome instability, which are key events in numerous of cancer types. Despite this, few studies have focused on the effect of nanomaterial exposure on telomere length as a possible mechanism involved in nanomaterial-induced carcinogenesis. In this study, effects of exposure to multiwalled carbon nanotubes (MWCNT) on telomere length were investigated in mice exposed by intrapleural injection, as well as in human lung epithelial and mesothelial cell lines. In addition, cell cycle, apoptosis, and regulation of genes i…

Spleen: Reparative Regeneration and Influence on Liver.

This review considers experimental findings on splenic repair, obtained in two types of small animal (mouse, rat, and rabbit) models: splenic resections and autologous transplantations of splenic tissue. Resection experiments indicate that the spleen is able to regenerate, though not necessarily to the initial volume. The recovery lasts one month and preserves the architecture, albeit with an increase in the relative volume of lymphoid follicles. The renovated tissues, however, exhibit skewed functional profiles; notably, the decreased production of antibodies and the low cytotoxic activity of

Intravital imaging reveals inflammation as a dominant pathophysiology of age-related hepatovascular changes.

Aging is the most significant risk factor for the majority of chronic diseases, including liver disease. The cellular, molecular, and pathophysiological mechanisms that promote age-induced hepatovascular changes are unknown due to our inability to visualize changes in liver pathophysiology in live mice over time. We performed quantitative liver intravital microscopy (qLIM) in live C57BL/6J mice to investigate the impact of aging on the hepatovascular system over a 24-mo period. qLIM revealed that age-related hepatic alterations include reduced liver sinusoidal blood flow, increased sinusoidal

Organ-on-chip of the cervical epithelial layer: A platform to study normal and pathological cellular remodeling of the cervix.

Damage to the cervical epithelial layer due to infection and inflammation is associated with preterm birth. However, the individual and/or collective roles of cervical epithelial layers in maintaining cervical integrity remain unclear during infection/inflammation. To determine the intercellular interactions, we developed an organ-on-chip of the cervical epithelial layer (CE-OOC) composed of two co-culture chambers connected by microchannels, recapitulating the ectocervical and endocervical epithelial layers. Further, we tested the interactions between cells from each distinct region and their

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas.

The formation of the skeleton occurs throughout the lives of vertebrates and is achieved through the balanced activities of two kinds of specialized bone cells: the bone-forming osteoblasts and the bone-resorbing osteoclasts. Impairment in the remodeling processes dramatically hampers the proper healing of fractures and can also result in malignant bone diseases such as osteosarcoma. MicroRNAs (miRNAs) are a class of small non-coding single-strand RNAs implicated in the control of various cellular activities such as proliferation, differentiation, and apoptosis. Their post-transcriptional regu

MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer.

The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the cons … on ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor …

Quantitative analysis of the expression of caspase 3 and caspase 9 in different types of atherosclerotic lesions in the human aorta.

The existing data on apoptotic processes in human atherosclerotic lesions is insufficient and is often contradictory. This study was underta … th the maximum being observed in fatty streaks. The fall in CASP3 expression may be associated with cellular senescence as well as with the domination of necrotic processes in atherosclerotic lesions, as shown by electron microscopic analysis. Our study provides novel quantitative data on the expression of CASP3 and CASP9 genes in different atherosclerotic lesions in …

Disc in flames: Roles of TNF-α and IL-1β in intervertebral disc degeneration.

The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc--incited by aging, traumatic insult, genetic predisposition, or other factors--is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, as well as compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly

Management of interstitial lung disease in elderly patients.

PURPOSE OF REVIEW: This review seeks to inform readers of evolving concepts of ageing-associated risks for developing interstitial lung disease (ILD) and current approaches to the diagnosis and management of ILD in elderly patients. RECENT FINDINGS: Various aspects of cellular and immune senescence have been identified that may explain the increased susceptibility of the elderly to developing fibrotic lung disease. New guidelines have been recently published concerning the diagnosis and management of idiopathic pulmonary fibrosis (IPF), which is highly prevalent in elderly patients. Nontransp

Single-cell and bulk transcriptomics identify senescence-related EMT transcriptional programs and a prognostic framework in pancreatic ductal adenocarcinoma.

BACKGROUND: Senescence-related transcriptional programs and epithelial-mesenchymal transition (EMT) are implicated in pancreatic ductal adenocarcinoma (PDAC) progression and therapy resistance. However, the single-cell distribution, functional heterogeneity, and clinical relevance of EMT-associated senescence-like programs remain incompletely defined. METHODS: We integrated single-cell RNA sequencing (scRNA-seq) data from 10 treatment-naive PDAC tumors with bulk transcriptomic profiles from TCGA-PAAD and an independent validation cohort. Senescence-related transcriptional activity was estimat

USP10-SIRT6-PARP1 axis drives keratinocyte senescence and skin photoaging under chronic UVA exposure.

Chronic exposure to ultraviolet A (UVA) radiation is the principal environmental driver of skin photoaging, yet the upstream molecular events that commit irradiated keratinocytes to senescence remain poorly understood. Here we show that SIRT6, an NAD+-dependent protein deacetylase with established roles in genome maintenance and organismal longevity, functions as a central gatekeeper of keratinocyte homeostasis under photic stress. Using a chronic UVA irradiation model in mice together with cultured human keratinocytes, we demonstrate that UVA inflicts extensive DNA damage and G2/M cell-cycle