Mechanical signaling in aging
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1266231 | ENA |
REPOSITORIES: ENA
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Project description:Aging is an independent risk factor for cardiovascular disease. Preventing age-induced arterial dysfunction and the associated risk of cardiovascular disease remains a significant clinical challenge. Aerobic exercise, which induces a temporary increase in both blood flow and pressure in active tissue, has been shown to reduce macroscale arterial stiffening in humans. The purpose of this study was to investigate the effects of mechanical stimuli on improving aging pathophysiology of VSM cells isolated from soleus feed arteries (SFA). We hypothesized that exposure to external mechanical stimulation enhances formation of smooth muscle alpha-actin (SMα-actin) fibers and cell-matrix adhesions in aged VSM cells. Ex-vivo functional studies were used to assess myogenic contractility of VSM in isolated SFA from young (4 months) and old (24 months) Fischer 344 rats. These data indicated that pre-treatment of isolated aged SFA with a short-duration increase in intraluminal pressure rescued contractility. The mechanical stretch-induced remodeling of the cellular architecture was assessed in VSM cells isolated from young and old SFA. To dissect the mechanisms involved, the structural and functional properties of VSM cells were assessed by using mechanical stimulation combined with fluorescence confocal microscopy. Results showed that aged VSM cells respond faster than young cells to 2D biaxial cyclic stretch by increasing actin stress fiber formation and vinculin recruitment at cell-matrix adhesions. In addition, hydrostatic pressure treatment applied to aged VSM cells plated on stiffer substrates restores actin fibers and integrin β1 recruitment. Taken together, these findings suggest that discrete VSM cell mechanical properties and their ability to adapt to external mechanical signals are key in restoring VSM contractility in aging. These results are significant because they provide a novel understanding of the mechanisms by which mechanical stimulation improves VSM contractility in aged resistance arteries. Our results provide new insights into the role of VSM in vascular aging and highlight a new direction for mitigating age-related effects via mechanical stimulation-induced VSM remodeling.
2025-07-07 | GSE297824 | GEO
Project description:Acute respiratory distress syndrome (ARDS) results in significant morbidity and mortality, especially in the elderly. Mechanical ventilation, a common supportive treatment for ARDS, is necessary for maintaining gas exchange, but can also propagate injury. We hypothesized that aging would exacerbate the pathophysiological responses to mechanical ventilation. Young and aged male mice were mechanically ventilated and changes in surfactant function, inflammation, and vascular permeability were assessed. Additionally, single-cell RNA sequencing was used to delineate cell-specific transcriptional changes. The results showed that surfactant dysfunction was augmented in aged mice, while inflammation was less pronounced in aged animals. Futhermore, vascular permeability was significantly increased with aging. Differential gene expression and pathway analyses revealed that aged endothelial cells exhibited altered cell-cell junction formation and that alveolar macrophages in aged mice showed a blunted inflammatory response. These results highlight the complex interplay between aging and mechanical ventilation, including an age-related predisposition to endothelial barrier dysfunction due to altered cell-cell junction formation and decreased inflammation, potentially due to immune exhaustion. It is concluded that age-related vascular changes may underlie the increased susceptibility to injury during mechanical ventilation in elderly patients.
2025-03-02 | GSE274828 | GEO
Project description:Impact of aging on pulmonary cellular responses during mechanical ventilation
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Project description:Aging of the vasculature is associated with detrimental changes in vascular smooth muscle cell (VSMC) mechanosensitivity to extrinsic forces in their surrounding microenvironment. However, how chronological aging alters VSMCs’ ability to sense and adapt to mechanical perturbations remains unexplored. Here, we show defective VSMC mechanosensation in aging measured with ultrasound tweezers-based micromechanical system, force instantaneous frequency spectrum and transcriptome analyses. The mechanobiological study reveals thataged VSMCs adapt a relatively inert solid-like state with altered actin cytoskeletal integrity, resulting in an impairment in their mechanosensitivity and dynamic mechanoresponse to mechanical perturbations. The aging-associated decline in mechanosensation behaviors is mediated by hyperactivity of Piezo1-dependent calcium signaling. Inhibition of Piezo1 alleviates vascular aging and partially restores the loss in dynamic contractile properties in aged cells. Altogether, our study reveals the novel signaling pathway underlying aging-associated aberrant mechanosensation in VSMC and identifies Piezo1 as a potential therapeutic mechanobiological target to alleviate vascular aging.
2024-02-21 | GSE230805 | GEO
Project description:Aging of the vasculature is associated with detrimental changes in vascular smooth muscle cell (VSMC) mechanosensitivity to extrinsic forces in their surrounding microenvironment. However, how chronological aging alters VSMCs’ ability to sense and adapt to mechanical perturbations remains unexplored. Here, we show defective VSMC mechanosensation in aging measured with ultrasound tweezers-based micromechanical system, force instantaneous frequency spectrum and transcriptome analyses. The mechanobiological study reveals thataged VSMCs adapt a relatively inert solid-like state with altered actin cytoskeletal integrity, resulting in an impairment in their mechanosensitivity and dynamic mechanoresponse to mechanical perturbations. The aging-associated decline in mechanosensation behaviors is mediated by hyperactivity of Piezo1-dependent calcium signaling. Inhibition of Piezo1 alleviates vascular aging and partially restores the loss in dynamic contractile properties in aged cells. Altogether, our study reveals the novel signaling pathway underlying aging-associated aberrant mechanosensation in VSMC and identifies Piezo1 as a potential therapeutic mechanobiological target to alleviate vascular aging.
2023-11-01 | GSE244111 | GEO
Project description:Mechanical stress is a measure of internal resistance exhibited by a body or material when external forces, such as compression, tension, bending, etc. are applied. The study of mechanical stress on health and aging is a continuously growing field, as major changes to the extracellular matrix and cell-to-cell adhesions can result in dramatic changes to tissue stiffness during aging and diseased conditions. For example, during normal aging, many tissues including the ovaries, skin, blood vessels, and heart exhibit increased stiffness, which can result in a significant reduction in function of that organ. As such, numerous model systems have recently emerged to study the impact of mechanical and physical stress on cell and tissue health, including cell-culture conditions with matrigels and other surfaces that alter substrate stiffness and ex vivo tissue models that can apply stress directly to organs like muscle or tendons. Here, we sought to develop a novel method in an in vivo, model organism setting to study the impact of mechanical stress on aging, by increasing substrate stiffness in solid agar medium of C. elegans. To our surprise, we found shockingly limited impact of growth of C. elegans on stiffer substrates, including limited effects on cellular health, gene expression, organismal health, stress resilience, and longevity. Overall, our studies reveal that altering substrate stiffness of growth medium for C. elegans have only mild impact on animal health and longevity; however, these impacts were not nominal and open up important considerations for C. elegans biologists in standardizing agar medium choice for experimental assays.
2024-04-05 | E-MTAB-13938 | biostudies-arrayexpress
Project description:Aging reduces liver resiliency by dysregulating Hedgehog signaling
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Project description:Proctor2016 - Circadian rhythm of PTH and the
dynamics of signaling molecules on bone remodeling
This model is described in the article:
Simulated Interventions to
Ameliorate Age-Related Bone Loss Indicate the Importance of
Timing.
Proctor CJ, Gartland A.
Front Endocrinol (Lausanne) 2016; 7:
61
Abstract:
Bone remodeling is the continuous process of bone resorption
by osteoclasts and bone formation by osteoblasts, in order to
maintain homeostasis. The activity of osteoclasts and
osteoblasts is regulated by a network of signaling pathways,
including Wnt, parathyroid hormone (PTH), RANK
ligand/osteoprotegrin, and TGF-?, in response to stimuli, such
as mechanical loading. During aging there is a gradual loss of
bone mass due to dysregulation of signaling pathways. This may
be due to a decline in physical activity with age and/or
changes in hormones and other signaling molecules. In
particular, hormones, such as PTH, have a circadian rhythm,
which may be disrupted in aging. Due to the complexity of the
molecular and cellular networks involved in bone remodeling,
several mathematical models have been proposed to aid
understanding of the processes involved. However, to date,
there are no models, which explicitly consider the effects of
mechanical loading, the circadian rhythm of PTH, and the
dynamics of signaling molecules on bone remodeling. Therefore,
we have constructed a network model of the system using a
modular approach, which will allow further modifications as
required in future research. The model was used to simulate the
effects of mechanical loading and also the effects of different
interventions, such as continuous or intermittent
administration of PTH. Our model predicts that the absence of
regular mechanical loading and/or an impaired PTH circadian
rhythm leads to a gradual decrease in bone mass over time,
which can be restored by simulated interventions and that the
effectiveness of some interventions may depend on their
timing.
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2024-09-02 | BIOMD0000000612 | BioModels