Faculty Opinions recommendation of Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan.

Extracellular vesicles (EVs) hold value as accessible biomarkers for understanding cellular differentiation and related pathologies. Herein, EV biomarkers in models of skeletal muscle dormancy and differentiation have been comparatively profiled using Raman spectroscopy (RS). Significant variations in the biochemical fingerprint of EVs were detected, with an elevation in peaks associated with lipid and protein signatures during early myogenic differentiation (day 2). Principal component analysis revealed a clear separation between the spectra of EVs derived from myogenic and senescent cell types, with non-overlapping interquartile ranges and population median. Observations aligned with nanoparticle tracking data, highlighting a significant early reduction in EV concentration in senescent myoblast cultures as well as notable variations in EV morphology and diameter. As differentiation progressed physical and biochemical differences in the properties of EVs became less pronounced. This study demonstrates the applicability of RS as a high-resolution analytical method for profiling biochemical changes in EVs during early myogenesis.

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The Role of Ageing and Parenchymal Senescence on Macrophage Function and Fibrosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.700790 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ross A. Campbell ◽

Marie-Helena Docherty ◽

David A. Ferenbach ◽

Katie J. Mylonas

Keyword(s):

Cell Types ◽

Senescent Cell ◽

Biological Impact ◽

Physiological Functions ◽

Macrophage Function ◽

Cell Clearance ◽

Indirect Impact

In this review, we examine senescent cells and the overlap between the direct biological impact of senescence and the indirect impact senescence has via its effects on other cell types, particularly the macrophage. The canonical roles of macrophages in cell clearance and in other physiological functions are discussed with reference to their functions in diseases of the kidney and other organs. We also explore the translational potential of different approaches based around the macrophage in future interventions to target senescent cells, with the goal of preventing or reversing pathologies driven or contributed to in part by senescent cell load in vivo.

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BIOMARKERS OF SENESCENT CELL BURDEN

Innovation in Aging ◽

10.1093/geroni/igz038.2048 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S555-S555

Author(s):

Nathan LeBrasseur

Keyword(s):

Severe Aortic Stenosis ◽

Cell Types ◽

Senescent Cell ◽

Adverse Outcomes ◽

Surrogate Endpoints ◽

Preclinical Studies ◽

Geriatric Syndromes ◽

Circulating Biomarkers ◽

Community Based ◽

Candidate Protein

Abstract Senescent cells drive aging. Preclinical studies suggest that targeted elimination of senescent cells offers a unique therapeutic approach to counter numerous chronic diseases and geriatric syndromes. To foster the translation of basic science discoveries to clinical application, we have sought to identify circulating biomarkers that reflect systemic senescent cell burden. We first analyzed the secretome of multiple senescent human cell-types and developed a candidate panel of proteins that could be reliably measured in human blood. Multiple proteins demonstrated significant associations with chronological age in a community-based cohort of adults aged 20-to-90 years. Impressively, in two distinct surgical cohorts (severe aortic stenosis and ovarian cancer), candidate protein concentrations were associated with biological age indices, including frailty and adverse outcomes. Our data suggest senescence biomarkers may have utility for clinical practice as indicators of risk, and for clinical research as surrogate endpoints in trials of interventions targeting senescent cells.

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