Adipose-Specific GHR Knockout Confers Multidimensional Anti-Aging Advantages via Adipose Tissue Remodeling and Enhanced Metabolic Elasticity
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PROVIDER: PRJNA1312478 | ENA |
REPOSITORIES: ENA
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Project description:The global growth hormone receptor knockout (GHR-/-) extends lifespan but causes adverse effects. Adipose tissue serves as a critical target organ for growth hormone (GH). Recent studies have suggested that GH signaling in adipose tissue influences aging progression, but the underlying regulatory mechanisms remain poorly understood. We generated adipose-specific GHR knockout mice (Ad-GHRKO; hereafter termed AKO) using 5-month-old and 20-month-old C57BL/6J males. The crucial function of adipose tissue GHR was examined by assessing age-related changes in mice during advanced aging. Adipose-specific GHR knockout extended healthspan through multifaceted geroprotection, manifested as significantly improved cognitive function, enhanced muscular/skeletal integrity, and a trend toward increased longevity. Mechanistically, adipose remodeling alleviated age-related lipid redistribution and restored glucose homeostasis, establishing a low-inflammation, high-plasticity depot that enhanced inter-tissue communication. Notably, we discovered that AKO mice exhibited significantly improved metabolic elasticity in adipose tissue. This enhancement is mechanistically linked to activation of the AMPK-SIRT1-Ac-PPARγ signaling axis. In vitro, pharmacological inhibition of AMPK abolished the beneficial effects of GHR ablation, confirming the central regulatory role of this pathway in maintaining adipose elasticity. These findings establish adipose GH signaling antagonism as a novel "metabolic elasticity switch" during aging, orchestrating adipose tissue to initiate reprogramming cascades that enhance metabolic elasticity and modulate healthspan through dynamic regulatory capacity rather than absolute activity levels, circumventing the adverse effects of systemic GH deficiency. These results resolve a critical knowledge gap in understanding how localized hormonal signaling in adipose tissue influences systemic aging trajectories. Our findings lay the foundation for developing targeted therapeutic strategies to mitigate age-related metabolic decline.
2025-09-05 | GSE306835 | GEO
Project description:We report that macrophage elasticity plays a dominant role in bacterial phagocytosis, release of TNF-alpha, and production of reactive oxygen species. We show that macrophage elasticity is modulated by mechanical factors including substrate rigidity and substrate stretch. Changes in macrophage elasticity are dependent upon the degree of actin polymerization, and mediated in part through small rhoGTPase activity. Moreover, the functional effects of macrophage elasticity are not predicted by gene expression profiles. Murine RAW 267.4 macrophages were separately grown on 2 matrix stiffness levels (1200, 150000 Pascals) for 0, 2, 6, 18 hours with 3 replicate sample experiments per condition. Total RNA extracted from the cells and profiled by microarrays. Keywords: Murine RAW 267.4 macrophage, matrix stiffness, phagocytosis, cell elasticity.
2012-03-28 | E-GEOD-36878 | biostudies-arrayexpress
Project description:We report that macrophage elasticity plays a dominant role in bacterial phagocytosis, release of TNF-alpha, and production of reactive oxygen species. We show that macrophage elasticity is modulated by mechanical factors including substrate rigidity and substrate stretch. Changes in macrophage elasticity are dependent upon the degree of actin polymerization, and mediated in part through small rhoGTPase activity. Moreover, the functional effects of macrophage elasticity are not predicted by gene expression profiles.
2012-03-29 | GSE36878 | GEO
Project description:Engineering nuclear elasticity to manipulate somatic cell fate
2025-12-02 | GSE224497 | GEO
Project description:Engineering nuclear elasticity to manipulate somatic cell fate
2025-12-02 | GSE224496 | GEO
Project description:Multidimensional Styela plicata microbiome
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Project description:Chromatin de-condensation by switching substrate elasticity
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Project description:Matrix elasticity influences differentiation of mesenchymal stem cells (MSCs) but it is unclear if these effects are only transient - while the cells reside on the substrate - or if they reflect persistent lineage commitment. In this study, MSCs were continuously culture-expanded in parallel either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on replicative senescence, in vitro differentiation, gene expression, and DNA methylation (DNAm) profiles. The maximal number of cumulative population doublings was not affected by matrix elasticity. Differentiation towards adipogenic and osteogenic lineage was increased on soft and rigid biomaterials, respectively - but this propensity was no more evident if cells were transferred to TCP. Global gene expression profiles and DNAm profiles revealed relatively few differences in MSCs cultured on soft or rigid matrices. Furthermore, only moderate DNAm changes were observed upon culture on very soft hydrogels of human platelet lysate. Our results support the notion that matrix elasticity influences cellular differentiation while the cells are organized on the substrate, but it does not have major impact on cell-intrinsic lineage determination, replicative senescence or DNAm patterns. MSCs cultivated either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on gene expression profiles.
2014-07-29 | E-GEOD-55867 | biostudies-arrayexpress
Project description:Matrix elasticity influences differentiation of mesenchymal stem cells (MSCs) but it is unclear if these effects are only transient - while the cells reside on the substrate - or if they reflect persistent lineage commitment. In this study, MSCs were continuously culture-expanded in parallel either on polydimethylsiloxane (PDMS) gels of different elasticity or on tissue culture plastic (TCP) to compare impact on replicative senescence, in vitro differentiation, gene expression, and DNA methylation (DNAm) profiles. The maximal number of cumulative population doublings was not affected by matrix elasticity. Differentiation towards adipogenic and osteogenic lineage was increased on soft and rigid biomaterials, respectively - but this propensity was no more evident if cells were transferred to TCP. Global gene expression profiles and DNAm profiles revealed relatively few differences in MSCs cultured on soft or rigid matrices. Furthermore, only moderate DNAm changes were observed upon culture on very soft hydrogels of human platelet lysate (hPL-gel). Our results support the notion that matrix elasticity influences cellular differentiation while the cells are organized on the substrate, but it does not have major impact on cell-intrinsic lineage determination, replicative senescence or DNAm patterns. 20 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip
2014-07-29 | E-GEOD-55888 | biostudies-arrayexpress
Project description:Nanoparticle elasticity plays crucial roles in determining nanoparticles’ physiological performances. However, the underlying mechanisms by which nanoparticle elasticity does so remain unknown.Using core-shell nanoparticles with a same PEGylated lipid bilayer shell yet cores differing in elasticity (45 kPa – 760 MPa) as the models, we isolated the effects of nanoparticle elasticity from those of other physiochemical parameters and observed a surprisingly non-monotonic relationship of nanoparticle elasticity versus nanoparticle systemic circulation lifetime, which segmented into three distinct regions depending on nanoparticle elasticity.
2022-05-20 | PXD034004 |