Cellular and molecular features of senescence in acute lung injury

Huidobro, Covadonga; Martín-Vicente, Paula; López-Martínez, Cecilia; Alonso-López, Inés; Amado-Rodríguez, Laura; Crespo, Irene; Albaiceta, Guillermo M.

doi:10.1016/j.mad.2020.111410

Cited by 7 publications

(7 citation statements)

References 133 publications

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“…Senescent responses during acute lung injury have been widely characterized [ 32 ]. An increase in P53-P21 signaling has been described in experimental models of acute inflammation and in humans with ARDS or receiving mechanical ventilation [ 33 ].…”

Section: The Short- and Long-term Consequences Of Senescencementioning

confidence: 99%

Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities

Martín-Vicente,

López-Martínez,

Rioseras

et al. 2024

Ann. Intensive Care

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Whereas aging is a whole-organism process, senescence is a cell mechanism that can be triggered by several stimuli. There is increasing evidence that critical conditions activate cell senescence programs irrespective of patient’s age. In this review, we briefly describe the basic senescence pathways and the consequences of their activation in critically ill patients. The available evidence suggests a paradigm in which activation of senescence can be beneficial in the short term by rendering cells resistant to apoptosis, but also detrimental in a late phase by inducing a pro-inflammatory and pro-fibrotic state. Senescence can be a therapeutic target. The use of drugs that eliminate senescent cells (senolytics) or the senescence-associated phenotype (senomorphics) will require monitoring of these cell responses and identification of therapeutic windows to improve the outcome of critically ill patients.

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Section: The Short- and Long-term Consequences Of Senescencementioning

confidence: 99%

Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities

Martín-Vicente,

López-Martínez,

Rioseras

et al. 2024

Ann. Intensive Care

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“…Acute lung injury (ALI) as a common lung disease with high mortality and incidence rates [ 1 , 2 , 3 , 4 ] is manifested by acute hypoxemic respiratory failure, increased alveolar permeability, and severe alveolar edema with normal cardiac filling pressures [ 5 ]. Due to inefficiency of traditional treatments for ALI [ 6 ], it is significant to develop a new therapeutic method for ALI to substantially reduce mortality and improve the quality of life of patients.…”

Section: Introductionmentioning

confidence: 99%

Artificial Intelligence-Assisted Terahertz Imaging for Rapid and Label-Free Identification of Efficient Light Formula in Laser Therapy

et al. 2022

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Photodynamic therapy (PDT) is considered a promising noninvasive therapeutic strategy in biomedicine, especially by utilizing low-level laser therapy (LLLT) in visible and near-infrared spectra to trigger biological responses. The major challenge of PDT in applications is the complicated and time-consuming biological methodological measurements in identification of light formulas for different diseases. Here, we demonstrate a rapid and label-free identification method based on artificial intelligence (AI)-assisted terahertz imaging for efficient light formulas in LLLT of acute lung injury (ALI). The gray histogram of terahertz images is developed as the biophysical characteristics to identify the therapeutic effect. Label-free terahertz imaging is sequentially performed using rapid super-resolution imaging reconstruction and automatic identification algorithm based on a voting classifier. The results indicate that the therapeutic effect of LLLT with different light wavelengths and irradiation times for ALI can be identified using this method with a high accuracy of 91.22% in 33 s, which is more than 400 times faster than the biological methodology and more than 200 times faster than the scanning terahertz imaging technology. It may serve as a new tool for the development and application of PDT.

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“…Cyclic stretch like the one generated by mechanical ventilation can break DNA strands down via MAPK activation [9], leading to upregulation of DNA damage proteins such as ɣH2AX [10]. Activation of ɣH2AX, in turn, will lead to the activation of P21 [11]. P38-MAPK is also known to activate the P53-P21 pathway resulting in cellular senescence [11].…”

Section: Introductionmentioning

confidence: 99%

“…Activation of ɣH2AX, in turn, will lead to the activation of P21 [11]. P38-MAPK is also known to activate the P53-P21 pathway resulting in cellular senescence [11]. However, this pathway has not been investigated in the context of senescence in acute diseases or VILI.…”

Section: Introductionmentioning

confidence: 99%

Mechanical Ventilation induced DNA Damage and P21 in an Acute Aging Model of Lung Injury

Gninzeko

Tho

Valentine

et al. 2022

Preprint

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Acute respiratory distress syndrome (ARDS) is a form of acute lung injury which leads to a paucity of oxygen. To remedy ARDS, patients are put on mechanical ventilators; however, the stretch resulting from the mechanical ventilator can lead to ventilator-induced lung injury or VILI. VILI is exacerbated by age. The combined effects of ARDS and mechanical ventilation can result in a hostile environment which may lead to senescence (stable cell cycle arrest). The role of senescence in VILI is poorly understood. Senescence is characterized by increased cyclin-dependent kinase inhibitors P16 and P21; however, P21 has been shown to occur in early senescence. We hypothesized that mechanical ventilation would lead to DNA damage and senescence-like phenotype. Both in vivo and in vitro models of VILI were used to investigate senescence and its mechanism in VILI. Mechanical ventilation increased senescence-associated markers such as DNA damage marker characterized by γH2AX, P21, senescence-associated secretory phenotype IL6, and decreased proliferation. Moreover, mechanical ventilation led to increased apoptosis. Lung sections were stained for KRT8 proteins, markers of transiently differentiated alveolar type 2 (AT2) cells which were reported to be more prone to DNA damage. Age and mechanical ventilation increased KRT8 positive cells. Finally, we probed a potential mediator of the stretch-induced senescence in vitro by inhibiting P38-MAPK, which can be activated by DNA damage response, leading to increased P21. Inhibiting P38 decreased in P21 but did not decrease ɣH2AXThese findings suggest that mechanical ventilation may lead to a senescence-like phenotype involving the P38-MAPK pathway.

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Cellular and molecular features of senescence in acute lung injury

Cited by 7 publications

References 133 publications

Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities

Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities

Artificial Intelligence-Assisted Terahertz Imaging for Rapid and Label-Free Identification of Efficient Light Formula in Laser Therapy

Mechanical Ventilation induced DNA Damage and P21 in an Acute Aging Model of Lung Injury

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