Extracellular Vesicles as “Very Important Particles” (VIPs) in Aging

Mas-Bargues, Cristina; Alique, Matilde

doi:10.3390/ijms24044250

Cited by 14 publications

(8 citation statements)

References 125 publications

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“…It has been well-documented that EVs are involved in aging processes through regulating multiple biogenesis pathways, such as cellular senescence, inflammation, tissue regeneration, oxidative stress, metabolism and autophagy ( 1 , 7 , 19 , 40 , 41 ). We have observed age-associated declines of multiple immune cell-related EV subpopulations in healthy humans and mice, consistent with an immunosenescence phenotype in healthy aging that is reflected in EV subpopulations ( 1 , 6 ).…”

Section: Discussionmentioning

confidence: 99%

Immune system-related plasma extracellular vesicles in healthy aging

Zhang,

Ma,

Huebner

et al. 2024

Front. Immunol.

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ObjectivesTo identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults.MethodsEV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers.ResultsCompared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1β, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1β, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation.ConclusionEndo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease.

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Section: Discussionmentioning

confidence: 99%

Immune system-related plasma extracellular vesicles in healthy aging

Zhang,

Ma,

Huebner

et al. 2024

Front. Immunol.

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“…A growing interest in the study of extracellular vesicles (EVs) was also discussed: [ 10 ] could these represent a signalling reservoir of ECM molecules that is disrupted in ageing? Are EVs maintained in tissues?…”

Section: Mechanisms and Interventionsmentioning

confidence: 99%

Strengths and opportunities in research into extracellular matrix ageing: A consultation with the ECMage research community

Dalby,

Pekovic‐Vaughan,

Shanley

et al. 2024

BioEssays

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Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three‐dimensional network of macromolecules that provides our tissues with structure and biomechanical resilience. Imbalance between damage and repair/regeneration causes the ECM to undergo structural deterioration with age, contributing to age‐associated pathology. The ECM ‘Ageing Across the Life Course’ interdisciplinary research network (ECMage) was established to bring together researchers in the United Kingdom, and internationally, working on the emerging field of ECM ageing. Here we report on a consultation at a joint meeting of ECMage and the Medical Research Council / Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, held in January 2023, in which delegates analysed the key questions and research opportunities in the field of ECM ageing. We examine fundamental biological questions, enabling technologies, systems of study and emerging in vitro and in silico models, alongside consideration of the broader challenges facing the field.

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“…The main hallmarks are genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, stem cell exhaustion, altered intercellular communication, and cellular senescence. EVs are involved in regulating some of these processes ( Table 1 ) [ 131 , 132 ].…”

Section: Evs As Integrators Of Homeostasismentioning

confidence: 99%

Utilizing Extracellular Vesicles for Eliminating ‘Unwanted Molecules’: Harnessing Nature’s Structures in Modern Therapeutic Strategies

Kisielewska,

Rakoczy,

Skowron

et al. 2024

Molecules

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Extracellular vesicles (EVs) are small phospholipid bilayer-bond structures released by diverse cell types into the extracellular environment, maintaining homeostasis of the cell by balancing cellular stress. This article provides a comprehensive overview of extracellular vesicles, their heterogeneity, and diversified roles in cellular processes, emphasizing their importance in the elimination of unwanted molecules. They play a role in regulating oxidative stress, particularly by discarding oxidized toxic molecules. Furthermore, endoplasmic reticulum stress induces the release of EVs, contributing to distinct results, including autophagy or ER stress transmission to following cells. ER stress-induced autophagy is a part of unfolded protein response (UPR) and protects cells from ER stress-related apoptosis. Mitochondrial-derived vesicles (MDVs) also play a role in maintaining homeostasis, as they carry damaged mitochondrial components, thereby preventing inflammation. Moreover, EVs partake in regulating aging-related processes, and therefore they can potentially play a crucial role in anti-aging therapies, including the treatment of age-related diseases such as Alzheimer’s disease or cardiovascular conditions. Overall, the purpose of this article is to provide a better understanding of EVs as significant mediators in both physiological and pathological processes, and to shed light on their potential for therapeutic interventions targeting EV-mediated pathways in various pathological conditions, with an emphasis on age-related diseases.

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Extracellular Vesicles as “Very Important Particles” (VIPs) in Aging

Cited by 14 publications

References 125 publications

Immune system-related plasma extracellular vesicles in healthy aging

Immune system-related plasma extracellular vesicles in healthy aging

Strengths and opportunities in research into extracellular matrix ageing: A consultation with the ECMage research community

Utilizing Extracellular Vesicles for Eliminating ‘Unwanted Molecules’: Harnessing Nature’s Structures in Modern Therapeutic Strategies

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