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Cellular survivorship bias as a mechanistic driver of muscle stem cell aging - PubMed
3 months ago
- Aging leads to a decline in tissue repair and regeneration, particularly in skeletal muscle.
- Muscle stem cells (MuSCs) show impaired function with age, affecting muscle regeneration.
- A cellular survivorship bias in aging MuSCs prioritizes survival over functionality.
- Aged MuSCs increase expression of NDRG1, a tumor suppressor, which suppresses the mTOR pathway.
- This suppression enhances long-term survival of MuSCs but delays their activation and muscle regeneration.
- The trade-off favors stem cell survival over immediate regenerative capacity, leading to delayed muscle repair.
MicroRNA profiles in plasma-derived extracellular vesicles across the human lifespan - PubMed
3 months ago
- Extracellular vesicles (EVs) are analyzed from a healthy aging cohort to study changes across the human lifespan.
- Older individuals show shifts in EV immunophenotype, indicating immunosenescence, and distinct miRNA signatures.
- Key miRNAs like miR-206, miR-143-3p, miR-122-5p, and miR-20b-3p are linked to muscle, metabolic, and vascular function.
- miR-6529-5p, associated with neuroprotection, is elevated in aging.
- EV miRNAs and particle counts correlate with biological aging markers such as GDF-15, visceral fat, and muscle quality.
- The study suggests EVs as potential minimally invasive biomarkers for biological aging and functional decline.
Mitochondrial double-stranded RNA drives aging-associated cognitive decline - PubMed
3 months ago
- Mitochondrial double-stranded RNA (mt-dsRNA) drives aging-associated cognitive decline.
- SEC61A1 regulates ER-mitochondria contact sites, affecting mitochondrial DNA and RNA synthesis.
- Changes in mt-dsRNA lead to innate immune signaling activation in aging and Alzheimer's disease.
- Overexpression of Sec61a1 in the mouse cortex induces cognitive decline without affecting motor activity.
- Knockdown of Sec61a1 or Mavs alleviates cognitive decline in aging mice by blocking mt-dsRNA signaling.
- The study provides a potential therapeutic target for aging- and disease-associated cognitive decline.
Hyperglutaminolysis drives senescence and aging through arginine-mTORC1 axis activation - PubMed
2 months ago
- Hyperglutaminolysis is hyperactivated in senescent cells and aged organisms like Drosophila and mice.
- This hyperactivation promotes aging, as shown by addition and removal intervention experiments.
- A novel signaling axis links hyperglutaminolysis to persistent mTORC1 activation via ammonium, glutamate, and arginine biosynthesis.
- Key enzymes GLS1 and ASL play regulatory roles in this cascade, verified by cellular and in vivo experiments.
- Dysregulated glutaminolysis is identified as a key driver of aging, connecting glutamine catabolism to mTORC1 activation.
Deletion of Mfn2 in endothelial cells triggers a mitohormetic response that improves systemic metabolism and healthspan in mice - PubMed
2 months ago
- Deletion of Mfn2 in endothelial cells (ECs) triggers a mitohormetic response, improving systemic metabolism and healthspan in mice.
- Mfn2 deficiency in ECs enhances antioxidant defenses, mitochondrial fitness, and lipid oxidation, leading to better metabolic outcomes.
- ECs secrete GDF15 via a FOXO1-dependent axis, observed both in vitro and in vivo under stress conditions.
- Mfn2i��EC mice showed elevated GDF15 levels, and GDF15 neutralization partly reversed metabolic benefits.
- Mfn2i��EC mice were protected against diet-induced obesity and age-related decline, highlighting vascular mitohormesis as a novel health-promoting mechanism.
Visceral adiposity, metabolic health and aging - PubMed
2 months ago
- Visceral adipose tissue (VAT) is a metabolically active organ linked to metabolic dysfunction and aging.
- VAT accumulation is both a biomarker and a causal contributor to impaired metabolic health and reduced lifespan.
- The pathogenicity of VAT is context-dependent, influenced by factors like lipid spillover, chronic inflammation, genetic susceptibility, hormonal changes, and aging.
- VAT-derived substances (cytokines, exosomes, adipokines, lipotoxic metabolites) mediate harmful effects on metabolic health.
- Strategies to reduce VAT burden or neutralize its pathological impact are emerging as promising approaches for promoting metabolic health and longevity.
Creatine plus β-Hydroxy-β-Methylbutyrate supplementation is associated with preserved glutathione redox-balance and redox-function associations in older adults: a secondary analysis of a randomized cr
2 months ago
- Combined creatine and β-Hydroxy-β-Methylbutyrate (HMB) supplementation may help preserve glutathione redox-balance in older adults.
- The study involved 30 physically active older adults (62.7 ± 5.3 years) in a randomized, double-blind, placebo-controlled crossover trial.
- Participants received either 3 g/day creatine + 3 g/day calcium HMB or placebo during supervised exercise training for 6-week phases.
- Primary endpoints included oxidized glutathione levels and the Glutathione Redox Index.
- Supplementation showed nominal preservation of redox balance, though effects were not significant after false discovery rate (FDR) adjustment.
- In men, a nominal increase in malondialdehyde was observed under supplementation.
- Exploratory analyses suggested weak associations between changes in redox indices and functional measures.
- The study supports further investigation in larger trials to confirm redox-function associations.
Aging-caused the changes of the gut microbiota drive intestinal barrier dysfunction and increase sepsis susceptibility - PubMed
2 months ago
- Aging-related changes in gut microbiota increase susceptibility to sepsis.
- Increased abundance of Klebsiella aerogenes (K. aero) in aged hosts leads to higher histamine (HA) production.
- Histamine exacerbates intestinal barrier dysfunction by inhibiting Nlrp6 expression and impairing autophagy.
- K. aero strains with a histidine decarboxylase gene variant are major HA producers.
- Modulating HA levels or overexpressing Nlrp6 reduces inflammation in septic mice.
- Targeting the HA-Nlrp6-LC3 axis could be a novel therapeutic approach for sepsis in aging populations.
Insolubilome profiling defines molecular features that influence protein insolubility with aging - PubMed
2 months ago
- Insolubilome profiling identifies molecular features affecting protein insolubility during aging.
- Mass spectrometry reveals tissue-specific insoluble/soluble protein ratios in young mice, varying widely (100-1,000×).
- Aging alters protein solubility: some proteins become more insoluble, others less, and some remain unaffected.
- Age-related solubility changes are not solely based on tissue similarity and differ in tissues with varying degeneration tendencies.
- Structural features correlate with tissue-specific changes in protein solubility with aging.
- Proteins becoming insoluble in multiple organs include aggregation-prone circulating factors and ectopically expressed proteins.
- Example: Hornerin, primarily expressed in epidermis, increases in insolubility in aging skeletal muscle; its upregulation causes muscle weakness.
- Age-insoluble proteins serve as biomarkers and may contribute to functional decline, indicating a complex remodeling of the insolubilome with aging.
Attenuating age-related decline in dendritic cell migration improves vaccine efficacy via gut-immune crosstalk - PubMed
2 months ago
- Aging impairs immune function and reduces vaccine efficacy.
- Dendritic cells (DCs) show migration defects in aged mice, contributing to diminished vaccine responses.
- Single-cell RNA sequencing reveals dysfunction-associated gene signatures in migratory DCs in aging.
- Oral yeast-derived nanoparticles boost CCR7 expression in gut DCs, improving their migration to lymph nodes.
- This strategy enhances vaccine-induced immunity in aged animals, offering a noninvasive method to improve vaccine efficacy.
Mapping the scientific landscape of mitochondria-associated membranes: a bibliometric insight into emerging frontiers in aging and diseases - PubMed
2 months ago
- Mitochondria-associated membranes (MAMs) play a crucial role in energy metabolism, lipid homeostasis, and Ca2+ signaling, influencing cell survival and stress responses.
- Dysfunction in MAMs is linked to aging, neurodegenerative diseases, metabolic disorders, and cancer.
- A bibliometric analysis of MAMs-related literature from 2009 to 2024 identified 1199 publications with a rapid annual growth rate of 21.57%.
- Research hotspots include Ca2+ homeostasis, ER stress, apoptosis, and mitochondrial dynamics, with a shift toward aging-related processes.
- Key findings highlight aging, ER stress, and apoptosis as interconnected emerging themes, with specific MAMs-related proteins like HSP90α identified as regulatory hubs.
- The study provides an integrative bibliometric framework, linking publication trends with biological pathways and suggesting future research directions.
Cellular Aging Signatures in the Plasma Proteome Record Human Health and Disease - PubMed
2 months ago
- Machine learning models estimate biological age of over 40 cell types using plasma proteomics.
- Study involves 7,000 plasma proteins from 60,000 individuals across three cohorts.
- 20-25% of individuals show accelerated aging in a single cell type; 1-3% in ten or more.
- APOE genotype has antagonistic aging effects: APOE4 carriers show older astrocytes but younger macrophages.
- Cellular aging signatures predict disease and mortality over 15 years.
- ALS strongly associated with skeletal myocyte aging (hazard ratio = 12.7).
- Alzheimer's disease linked to accelerated aging in multiple neural and peripheral cell types.
- Extreme astrocyte aging increases Alzheimer's risk, especially in APOE4/4 carriers.
- Respiratory cell aging identifies smokers at higher lung cancer risk.
- Myeloid aging predicts diabetes risk in normoglycemic individuals.
- Polycellular aging risk score provides robust mortality risk stratification.
Modeling the Aging Human Lung: Generation of a Senescent Human Lung Organoid Culture System - PubMed
2 months ago
- The study focuses on modeling the aging human lung by creating a senescent human lung organoid culture system.
- Senescence in the aging lung leads to chronic inflammation and fibrosis, contributing to diseases like COPD and IPF.
- Researchers generated a human iPSC-derived lung organoid system, inducing senescence with doxorubicin.
- Senescent cells showed increased β-galactosidase activity, pro-inflammatory cytokine production, and impaired barrier integrity.
- The model replicates key aspects of lung senescence, useful for studying age-related lung diseases and potential treatments.
Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging - PubMed
2 months ago
- A single-cell chromatin accessibility atlas was created for 21 mouse tissues across three age groups and both sexes.
- Around 25% of 536 organ-specific cell types and 1828 finer-grained subtypes showed significant age-related population shifts.
- Cellular states from broadly distributed lineages exhibited synchronized dynamics with age, suggesting systemic coordination.
- Both intrinsic regulators (chromatin peaks, transcription factor activity) and extrinsic factors (cytokine programs) were identified as underlying these shifts.
- Approximately 40% of aging-associated population dynamics were sex-dependent, with thousands of peaks altered exclusively in one sex.
- The study provides a comprehensive framework for understanding how aging reshapes chromatin landscape and cellular composition across diverse tissues.
Ribonuclease κ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules - PubMed
2 months ago
- Ribonuclease κ (RNASEK) prevents age-dependent accumulation of circular RNAs (circRNAs) by promoting their degradation.
- RNASEK is downregulated during aging, leading to increased circRNA levels.
- RNASEK is necessary and sufficient for lifespan extension and healthspan maintenance in Caenorhabditis elegans.
- Mammalian RNASEK also degrades circRNAs and prevents premature aging in human cells and mice.
- CircRNAs localize within stress granules, where RNASEK collaborates with HSP90 to prevent toxic aggregation in aged organisms.
- RNASEK is identified as a conserved regulator of aging, offering a strategy to target circRNAs for mitigating age-associated diseases.
Select Small Non-Coding RNAs Are Determinants of Survival in Older Adults - PubMed
2 months ago
- Study investigates small non-coding RNAs (smRNAs) as determinants of survival in older adults.
- Evaluated 828 smRNAs (687 miRNAs and 141 piRNAs) in plasma from 1,271 older adults (≥71 years).
- Predictive model combining smRNAs, clinical variables, and age achieved high accuracy (AUC 0.92 for 2-year survival).
- Nine piRNAs, reduced in longer-lived individuals, identified as potential therapeutic targets.
- Findings suggest circulating piRNAs and miRNAs as biomarkers and therapeutic targets for human longevity.
- Reduced piRNA biogenesis linked to doubled lifespan in C. elegans, supporting biological plausibility.
Dysregulated Klotho and FGF23 signaling aggravates vascular remodeling in age-related pulmonary hypertension - PubMed
2 months ago
- Pulmonary arterial hypertension (PAH) is a chronic condition caused by vascular remodeling due to increased proliferation of pulmonary arterial smooth muscle cells (PASMC).
- Initially affecting young women, PAH now increasingly affects the elderly, but age-related mechanisms remain unclear.
- The study explores the role of the anti-aging protein Klotho and fibroblast growth factor 23 (FGF23) in PAH pathogenesis.
- Aged mice and Klotho-deficient mice showed moderate PAH, right ventricular hypertrophy, and dysfunction, worsened by hypoxia.
- Elevated plasma FGF23 levels were found in aged mice, Klotho-deficient mice, and elderly PAH patients.
- FGF23 increased PASMC proliferation, which was prevented by fibroblast growth factor receptor 1 knockdown.
- Neutralizing FGF23 in Klotho-deficient mice reduced PAH symptoms and vascular remodeling.
- The study identifies FGF23 accumulation as a novel mechanism in PAH vascular remodeling.
- Targeting dysregulated Klotho/FGF23 signaling may offer a therapeutic strategy for elderly PAH patients.
Aging of the Blood-Brain Barrier and Altered Permeability to Peripheral Immune Cells: Implications for Central Nervous System Disorders - PubMed
2 months ago
- The blood-brain barrier (BBB) maintains CNS homeostasis and regulates immune cell entry.
- Aging leads to BBB degradation through tight junction downregulation, pericyte loss, and other structural changes.
- Altered BBB permeability causes dysregulated immune cell entry, leading to neuroinflammation and neurodegeneration.
- These changes contribute to diseases like Alzheimer's, Parkinson's, and vascular dementia.
- Potential interventions include repairing tight junctions, restoring pericyte function, and modulating immune responses.
- Early diagnosis and targeted therapies could mitigate CNS disorders.
Immunometabolic resistors of aging in long-lived golden spiny mice - PubMed
2 months ago
- Long-lived golden spiny mice (Acomys russatus) resist functional decline and show reduced senescence in immune-metabolic organs compared to their sister species, Acomys dimidiatus.
- Aged A. russatus maintains transcriptional integrity similar to young mice, highlighting key checkpoints for inflammation and mortality.
- Elevated levels of clusterin in A. russatus macrophages help restrain inflammaging and enhance health span in aged mice.
- The study suggests that A. russatus biology reveals potential therapeutic targets to maintain or enhance function during aging.
The gut and circulating virome: emerging players in aging and longevity - PubMed
2 months ago
- The human virome, including gut and circulating viruses, plays a critical role in host physiology and aging.
- Age-related shifts in the virome include changes in bacteriophage families, latent virus reactivation, and persistence of viral pathobionts.
- These virome changes are linked to immunosenescence, chronic inflammation, and neurodegeneration.
- Centenarians exhibit a unique virome signature with increased diversity, lytic activity, and phage-encoded metabolic functions, suggesting a protective role in longevity.
- Challenges in virome research include technical biases, database limitations, and the presence of 'viral dark matter'.
- The review emphasizes the virome's relevance in Geroscience and discusses barriers to translating research into clinical aging studies.

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#aging

Cellular survivorship bias as a mechanistic driver of muscle stem cell aging - PubMed

MicroRNA profiles in plasma-derived extracellular vesicles across the human lifespan - PubMed

Mitochondrial double-stranded RNA drives aging-associated cognitive decline - PubMed

Hyperglutaminolysis drives senescence and aging through arginine-mTORC1 axis activation - PubMed

Deletion of Mfn2 in endothelial cells triggers a mitohormetic response that improves systemic metabolism and healthspan in mice - PubMed

Visceral adiposity, metabolic health and aging - PubMed

Creatine plus β-Hydroxy-β-Methylbutyrate supplementation is associated with preserved glutathione redox-balance and redox-function associations in older adults: a secondary analysis of a randomized cr

Aging-caused the changes of the gut microbiota drive intestinal barrier dysfunction and increase sepsis susceptibility - PubMed

Insolubilome profiling defines molecular features that influence protein insolubility with aging - PubMed

Attenuating age-related decline in dendritic cell migration improves vaccine efficacy via gut-immune crosstalk - PubMed

Mapping the scientific landscape of mitochondria-associated membranes: a bibliometric insight into emerging frontiers in aging and diseases - PubMed

Cellular Aging Signatures in the Plasma Proteome Record Human Health and Disease - PubMed

Modeling the Aging Human Lung: Generation of a Senescent Human Lung Organoid Culture System - PubMed

Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging - PubMed

Ribonuclease κ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules - PubMed

Select Small Non-Coding RNAs Are Determinants of Survival in Older Adults - PubMed

Dysregulated Klotho and FGF23 signaling aggravates vascular remodeling in age-related pulmonary hypertension - PubMed

Aging of the Blood-Brain Barrier and Altered Permeability to Peripheral Immune Cells: Implications for Central Nervous System Disorders - PubMed

Immunometabolic resistors of aging in long-lived golden spiny mice - PubMed

The gut and circulating virome: emerging players in aging and longevity - PubMed