Guidelines for minimal information on cellular senescence experimentation in vivo

Cell, Journal Year: 2024, Volume and Issue: 187(16), P. 4150 - 4175

Published: Aug. 1, 2024

Cellular senescence is a cell fate triggered in response to stress and characterized by stable cell-cycle arrest hypersecretory state. It has diverse biological roles, ranging from tissue repair chronic disease. The development of new tools study vivo paved the way for uncovering its physiological pathological roles testing senescent cells as therapeutic target. However, lack specific broadly applicable markers makes it difficult identify characterize tissues living organisms. To address this, we provide practical guidelines called "minimum information cellular experimentation vivo" (MICSE). presents an overview rodent tissues, transgenic models, non-mammalian systems, human tumors their use identification specification cells. These uniform, state-of-the-art, accessible toolset improve our understanding vivo.

Language: Английский

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Nanocarriers for natural polyphenol senotherapeutics

Aging Cell, Journal Year: 2024, Volume and Issue: 23(5)

Published: April 29, 2024

Abstract Senescence is a heterogenous and dynamic process in which various cell types undergo cell‐cycle arrest due to cellular stressors. While senescence has been implicated aging many human pathologies, therapeutic interventions remain inadequate the absence of comprehensive set biomarkers context‐dependent manner. Polyphenols have investigated as senotherapeutics both preclinical clinical settings. However, their use hindered by limited stability, toxicity, modest bioavailability, often concentration at target sites. To address these limitations, nanocarriers such polymer nanoparticles lipid vesicles can be utilized enhance efficacy senolytic polyphenols. Focusing on widely studied agents—specifically fisetin, quercetin, resveratrol—we provide concise summaries physical chemical properties, along with an overview findings. We also highlight common signaling pathways potential toxicities associated agents. Addressing challenges linked nanocarriers, we present examples senotherapeutic delivery types, without nanocarriers. Finally, continued research development agents are encouraged reduce undesirable effects different organs. This review underscores need for establishing reliable sets that could assist evaluating effectiveness current future candidates

Language: Английский

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Addition of Polyphenols to Drugs: The Potential of Controlling “Inflammaging” and Fibrosis in Human Senescent Lung Fibroblasts In Vitro

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7163 - 7163

Published: June 28, 2024

The combination of a polyphenol, quercetin, with dasatinib initiated clinical trials to evaluate the safety and efficacy senolytics in idiopathic pulmonary fibrosis, lung disease associated presence senescent cells. Another approach senotherapeutics consists controlling inflammation related cellular senescence or “inflammaging”, which participates, among other processes, establishing fibrosis. We whether polyphenols such as caffeic acid, chlorogenic epicatechin, gallic resveratrol combined different metformin rapamycin, antifibrotic drugs nintedanib pirfenidone, could present beneficial actions an vitro model MRC-5 fibroblasts. A senescent-associated secretory phenotype (SASP) was evaluated by measurement interleukin (IL)-6, IL-8, IL-1β. β-galactosidase (SA-β-gal) activity proliferation were assessed. Fibrosis using Picrosirius red assay gene expression fibrosis-related genes. Epithelial-mesenchymal transition (EMT) assayed A549 cell line exposed Transforming Growth Factor (TGF)-β vitro. that demonstrated best results inhibiting IL-6 IL-8 Metformin acid also restore reduce SA-β-gal during induction. collagen production cells inhibited epicatechin alone drugs. Epicatechin able control EMT In conclusion, can potentially increase effectiveness senotherapeutic diseases whose pathophysiological component is

Language: Английский

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Nicotinamide metabolism reprogramming drives reversible senescence of glioblastoma cells

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: March 21, 2025

Recent studies show that metabolites, beyond their metabolic roles, can induce significant changes in cell behavior. Herein, we investigate the non-canonical role of nicotinamide (vitamin B3) on glioblastoma (GB) Nicotinamide induced senescence GB cells, characterized by reduced proliferation, chromatin reorganization, increased DNA damage, enhanced beta-galactosidase activity, and decreased Lamin B1 expression. Nicotinamide-induced was accompanied an unexpected reprogramming its metabolism, marked simultaneous downregulated transcription NNMT (nicotinamide N-methyltransferase) NAMPT phosphoribosyl-transferase). effects cells were mediated levels SOX2. Consistently, analyses patients' single transcriptome datasets showed with low expression enriched gene modules related to senescence. Remarkably, senescent retained tumor-forming ability vivo, albeit a lesser extent compared control cells. Further experiments at single-cell level transcriptomic demonstrated nicotinamide-induced is fully reversible. Overall, our findings identify novel reversible state tumors highlight as key driver cancer plasticity.

Language: Английский

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Cells of all trades – on the importance of spatial positioning of senescent cells in development, healing and aging

FEBS Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

Biological processes are often spatially regulated, ensuring molecular and cellular events occur in their most strategically advantageous locations. Cellular senescence, marked by cell cycle arrest hypersecretion, is recognized as an important part of physiological like development healing, but it also contributes to aging disease. However, the spatial distribution senescent cells its pathological impact remain unclear. Here we compile evidence on localization development, aging. We emphasize significance patterns speculate effects disrupted positioning senescence relation pathologies. To summarize specific functions cells, propose refer them 'barrier' 'conductor' functions. The function due altered morphology apoptosis resistance, separates tissues builds a border between two environments. conductor function, with secretion signaling factors, influences surrounding area stimulates migration, differentiation, or proliferation, among other processes. Overall, this Review explores patterning biological processes, highlighting dual roles functions, examines implications aging,

Language: Английский

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Lactiplantibacillus plantarum CCFM8661 alleviates d-galactose-induced brain aging in mice by the regulation of the gut microbiota

Food & Function, Journal Year: 2023, Volume and Issue: 14(22), P. 10135 - 10150

Published: Jan. 1, 2023

Lactiplantibacillus plantarum CCFM8661 alleviates D-galactose induced aging in mice.

Language: Английский

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2′-O-ribose methylation levels of ribosomal RNA distinguish different types of growth arrest in human dermal fibroblasts

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(3)

Published: Feb. 1, 2024

ABSTRACT The 2′-O-methylation (2′-O-Me) of ribosomal RNA (rRNA) shows plasticity that is potentially associated with cell phenotypes. We used RiboMeth-seq profiling to reveal growth arrest-specific 2′-O-Me patterns in primary human dermal fibroblasts from three different donors. exposed cells hydrogen peroxide induce cellular senescence and high densities promote quiescence by contact inhibition. compared both modes cycle arrest proliferating could indeed distinguish these conditions their overall patterns. Methylation levels at a small fraction sites showed correlated the expression specific nucleolar RNAs (snoRNAs) but not fibrillarin. Moreover, we observed subtle senescence-associated alterations ribosome biogenesis. Knockdown snoRNA SNORD87, which acts as guide for modification hypermethylated position non-proliferating cells, was sufficient boost proliferation. Conversely, depletion SNORD88A, SNORD88B SNORD88C, act guides hypomethylated site, caused decreased proliferation without affecting global protein synthesis or apoptosis. Taken together, our findings provide evidence rRNA modifications can be influence phenotypes cells.

Language: Английский

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Profiling microRNA expression during senescence and aging: mining for a diagnostic tool of senescent-cell burden

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 10, 2024

Abstract In the last decade cellular senescence, a hallmark of aging, has come into focus for pharmacologically targeting aging processes. Senolytics are one these interventive strategies that have advanced clinical trials, creating an unmet need minimally invasive biomarkers senescent cell load to identify patients at senotherapy. We created landscape miRNA and mRNA expression in five human types induced senescence in-vitro provide proof-of-principle evidence can track burden dynamically in-vivo using transgenic p21 high clearance HFD fed mice. Finally, we profiled seven different tissues, total plasma, plasma derived EVs young 25 months old systematic analysis, identified 22 candidate senomiRs with potential serve as circulating not only rodents, but also upcoming senolytic trials.

Language: Английский

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The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity

Published: May 30, 2024

Cellular senescence accumulates with age and has been shown to impact numerous physiological pathological processes, including immune function. The role of cellular in cancer is multifaceted, but the on checkpoint inhibitor response toxicity not fully evaluated. In this review, we evaluate various biological compartments, tumor, tumor microenvironment, system efficacy toxicity. We provide an overview normal contexts examine recent studies that have connected aging treatment both pre-clinical clinical contexts. Overall, plays a multi-faceted, context-specific role, modulate immune-related adverse event incidence as well response.

Language: Английский

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Comparative evaluation of cellular senescence in naturally aged and stress-induced murine macrophages for identifying optimum senescent macrophage study systems

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Jan. 15, 2025

Language: Английский

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