Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone?

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 99 - 99

Published: Jan. 16, 2025

Cellular senescence is a state of permanent cell cycle arrest accompanied by metabolic activity and characteristic phenotypic changes. This process crucial for developing age-related diseases, where excessive calorie intake accelerates dysfunction aging. Overnutrition disturbs key pathways, including insulin/insulin-like growth factor signaling (IIS), the mammalian target rapamycin (mTOR), AMP-activated protein kinase. The dysregulation these pathways contributes to insulin resistance, impaired autophagy, exacerbated oxidative stress, mitochondrial dysfunction, further enhancing cellular systemic derangements. On other hand, dysfunctional endothelial cells adipocytes contribute inflammation, reduced nitric oxide production, altered lipid metabolism. Numerous factors, extracellular vesicles, mediate pathological communication between vascular system adipose tissue, amplifying imbalances. Meanwhile, caloric restriction (CR) emerges as potent intervention counteract overnutrition effects, improve function, reduce restore balance. CR modulates such IIS, mTOR, sirtuins, glucose metabolism, reducing promoting autophagy. can extend health span mitigate diseases delaying improving healthy endothelial-adipocyte interactions. review highlights crosstalk adipocytes, emphasizing potential in counteracting overnutrition-induced restoring homeostasis.

Language: Английский

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From bench to bedside: translational insights into aging research

Frontiers in Aging, Journal Year: 2025, Volume and Issue: 6

Published: Jan. 24, 2025

Aging research has rapidly advanced from fundamental discoveries at the molecular and cellular levels to promising clinical applications. This review discusses critical translational insights that bridge gap between bench bedside applications, highlighting key in mechanisms of aging, biomarkers, therapeutic interventions. It underscores importance interdisciplinary approaches collaboration among scientists, clinicians, policymakers address complexities aging improve health span.

Language: Английский

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Serum Growth Differentiation Factor 15 is Negatively Associated with Leukocyte Telomere Length

The journal of nutrition health & aging, Journal Year: 2025, Volume and Issue: 29(4), P. 100493 - 100493

Published: Feb. 3, 2025

Telomere length(TL)and mitochondrial DNA copy number(mtDNAcn) are classic biomarker of aging. Recently, growth differentiation factor 15(GDF15) has attracted considerable attention as a vital component in the aging process. The present study aimed to relationship between GDF15 and telomere length mtDNAcn.This was cross-sectional analysis nested longitudinal cohort conducted Changping District, Beijing, from 2014 2021. Serum GDF15,leukocyte lelomere length(LTL) mtDNAcn were determined 802 subjects.LTL quantified by real-time PCR assay. Multivariate linear regression restricted cubic spline diagram used for statistical analysis. Subjects with higher older,had larger waist circumference, systolic blood pressure glycated hemoglobin A1c (HbA1c),shorter LTL tended had less mtDNAcn. In correlation analysis, positively correlated age, while negatively age.After adjusting confounding factors,GDF15 associated (β = -0.120, 95%CI [-0.197, -0.042], p 0.003) association linear(p nonlinear 0.645), negative did not reach significance.In stratified analyses,the associations more prominent women, overweight individuals, or subjects abnormal glucose tolerance (AGT), but similar results observed younger older subjects. This found GDF 15 LTL,which AGT subjects.These supported that might be reliable

Language: Английский

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Neuroprotective insights into epigallocatechin gallate (EGCG) for neurodegenerative disorders

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Neurodegenerative disorders, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are among the most significant health concerns worldwide, characterized by neuronal dysfunction, oxidative stress, neuroinflammation, protein misfolding. Epigallocatechin gallate, a green tea polyphenol, has been reported to possess multifaceted neuroprotective properties. It reduces stress through free radical scavenging, activation of antioxidant enzymes, stabilization mitochondrial function. also inhibits neuroinflammation modulation key signaling pathways. suppresses amyloid-beta aggregation in Alzheimer’s alpha-synuclein fibrillation thus attenuating toxic accumulation. Its activity induction autophagy promotion synaptic plasticity supports survival However, low bioavailability metabolic instability hinder its translation into clinic. Strategies nanoparticle encapsulation, structural modifications, combination therapies being explored overcome these challenges. Future research could establish epigallocatechin gallate as viable candidate for managing neurodegenerative disorders.

Language: Английский

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Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 302 - 302

Published: Feb. 28, 2025

Excessive alcohol consumption significantly impacts human health, particularly the brain, due to its susceptibility oxidative stress, which contributes neurodegenerative conditions. Alcohol metabolism in brain occurs primarily via catalase, followed by CYP2E1 pathways. Excess metabolized generates reactive oxygen/nitrogen species (ROS/RNS), leading cell injury altering many different Elevated stress impairs autophagic processes, increasing post-translational modifications and further exacerbating mitochondrial dysfunction ER death. The literature highlights that alcohol-induced disrupts autophagy mitophagy, contributing neuronal damage. Key mechanisms include dysfunction, epigenetics, accumulation of oxidatively modified proteins, lead neuroinflammation impaired cellular quality control. These processes are exacerbated chronic exposure, resulting suppression protective pathways like NRF2-mediated antioxidant responses increased changes brain. Alcohol-mediated neurotoxicity involves complex interactions between metabolism, regulation, influenced various factors such as drinking patterns, nutritional status, genetic/environmental factors, highlighting need for molecular studies unravel these develop targeted interventions.

Language: Английский

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Obesity accelerates cardiovascular ageing

European Heart Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract A global obesity pandemic, coupled with an increasingly ageing population, is exacerbating the burden of cardiovascular disease. Indeed, clinical and experimental evidence underscores a potential connection between in pathogenesis various disorders. This further supported by notion that weight reduction not only effectively reduces major events elderly individuals but also considered gold standard for lifespan extension, obese non-obese model organisms. review evaluates intricate interplay from molecular mechanisms to whole organ function within system. By comparatively analysing their characteristic features, shared cell biological signatures are unveiled, intent shed light on how accelerates ageing. elaborates emerging metabolic interventions targeting might protect diseases largely through antagonizing key process itself. In sum, this aims provide valuable insight into understanding these interconnected processes could guide development novel effective therapeutics growing aged population concerning problem.

Language: Английский

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Polyploidy-mediated resilience in hepatic aging: molecular mechanisms and functional implication

Egyptian Liver Journal, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 12, 2024

Abstract Background Polyploidization, a process where cells acquire additional chromosome sets, is unique characteristic of hepatocytes. This has been increasingly recognized as an adaptive mechanism for maintaining liver function during aging, period characterized by cellular senescence, DNA damage, and metabolic dysregulation. Purpose review explores the molecular mechanisms underlying hepatocyte polyploidization its potential role in promoting resilience against aging-related decline function. We assess how polyploid hepatocytes contribute to genomic stability, stress resistance, adaptation, highlighting their relevance aging. Main body Hepatocyte occurs through such cytokinesis failure endoreplication, leading binuclear or mononuclear cells. Polyploid exhibit enhanced repair capacity, which helps mitigate accumulation age-related damage. The increased gene dosage facilitates better responses, particularly oxidative genotoxic insults. Metabolic adaptations, including xenobiotic metabolism lipid regulation, further support liver’s ability maintain homeostasis Additionally, demonstrate altered epigenetic landscapes proteostasis mechanisms, contributing improved reduced susceptibility senescence. These adaptations collectively enhance structural challenges. Conclusion represents critical protective that safeguard instability, dysfunction, stress. Understanding pathways driving could pave way novel therapeutic strategies combat disorders health span. Graphical

Language: Английский

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Pioneering Advances and Innovative Applications of Mesoporous Carriers for Mitochondria-Targeted Therapeutics

British Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 81

Published: Nov. 18, 2024

Mitochondria, known as the cell’s powerhouse, play a critical role in energy production, cellular maintenance, and stemness regulation non-cancerous cells. Despite their importance, using drug delivery systems to target mitochondria presents significant challenges due several barriers, including uptake limitations, enzymatic degradation, mitochondrial membranes themselves. Additionally, barriers organs be targetted, along with extracellular formed by physiological processes such reticuloendothelial system, contribute rapid elimination of nanoparticles designed for mitochondrial-based delivery. Overcoming these has led development various strategies, molecular targeting cell-penetrating peptides, genomic editing, nanoparticle-based systems, porous carriers, liposomes, micelles, Mito-Porters. Porous carriers stand out particularly promising candidates large pore size, surface area, ease functionalisation. Depending on they can classified micro-, meso-, or macroporous are either ordered non-ordered based both size uniformity. Several methods employed modifications polyethylene glycol (PEG), incorporation ligands like triphenylphosphonium, capping pores gold chitosan enable controlled triggered Photodynamic therapy is another approach, where drug-loaded generate reactive oxygen species (ROS) enhance targeting. Further advancements have been made form functionalised silica carbon nanoparticles, which demonstrated potential effective mitochondria. This review highlights approaches that utilise specifically focusing silica-based efficient vehicles mitochondria, paving way improved strategies therapies.

Language: Английский

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Antisenescence Expansion of Mesenchymal Stem Cells Using Piezoelectric β-Poly(vinylidene fluoride) Film-Based Culture

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(46), P. 63207 - 63224

Published: Nov. 6, 2024

Regenerative therapies based on mesenchymal stem cells (MSCs) show promise in treating a wide range of disorders. However, the replicative senescence MSCs during vitro expansion poses challenge to obtaining substantial quantity high-quality MSCs. In this investigation, piezoelectric β-poly(vinylidene fluoride) film-based culture plate (β-CP) was developed with an antisenescence effect cultured human umbilical cord-derived Compared traditional tissue plates (TCPs) and α-poly(vinylidene plates, markers p21, p53, interleukin-6 insulin-like growth factor-binding protein-7, stemness OCT4 NANOG, telomere length β-CPs were significantly improved. Additionally, at passage 18 showed better multipotency pro-angiogenic capacities vitro, higher wound healing abilities mouse model. Mechanistically, rejuvenated senescent by improving mitochondrial functions mitigating oxidative glycoxidative stresses. Overall, study presents as promising approach for efficient straightforward while preserving their stemness, thereby holding great potential large-scale production clinical application cell therapies.

Language: Английский

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