Metabolic regulation of immune cells in proinflammatory microenvironments and diseases during ageing

Li, Peiheng; Zhang, Ran; Cheng, Liqin; Liu, Jinjing; Chen, Hou-Zao

doi:10.1016/j.arr.2020.101165

Cited by 13 publications

(9 citation statements)

References 159 publications

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“…To increase senescent LSECs in the late stage of regeneration, macrophages were removed systemically by clodronate. [ 29 ] Both IF staining (Figure 2D) and FACS (Figure 2E) showed that most liver macrophages could be successfully depleted. Next, we administered a single injection of clodronate on day 10 after pHx and analyzed its effect on liver recovery on day 14.…”

Section: Resultsmentioning

confidence: 99%

Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis

et al. 2021

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Background and Aims:The mechanisms involved in liver regeneration after partial hepatectomy (pHx) are complicated. Cellular senescence, once linked to aging, plays a pivotal role in wound repair. However, the regulatory effects of cellular senescence on liver regeneration have not been fully elucidated. Approach and Results: Mice subjected to pHx were analyzed 14 days after surgery. The incomplete remodeling of liver sinusoids affected shear stressinduced endothelial nitric oxide synthase (eNOS) signaling on day 14, resulting in the accumulation of senescent LSECs. Removing macrophages to augment LSEC senescence led to a malfunction of the regenerating liver. A dynamic fluctuation in Notch activity accompanied senescent LSEC accumulation during liver regeneration. Endothelial Notch activation by using Cdh5-CreERT NIC eCA mice triggered LSEC senescence and senescence-associated secretory phenotype, which disrupted liver regeneration. Blocking the Notch by γ-secretase inhibitor (GSI) diminished senescence and promoted LSEC expansion. Mechanically, Notch-hairy and enhancer of split 1 signaling inhibited sirtuin 1 (Sirt1) transcription by binding to its promoter region. Activation of Sirt1 by SRT1720 neutralized the up-regulation of P53, P21, and P16 caused by Notch activation and eliminated Notch-driven LSEC senescence. Finally, Sirt1 activator promoted liver regeneration by abrogating LSEC senescence and improving sinusoid remodeling.

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Section: Resultsmentioning

confidence: 99%

Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis

et al. 2021

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“…Additionally, opposite alterations in CS scores post-ICB treatment between responders and nonresponders at the single-cell level, together with significant correlations of PD-L1 and p21 expression in the IHC assay, further support the capabilities of the CS score to predict ICB responses effectively. As discussed in our review [ 81 ] and preclinical success in pancreas cancer [ 82 ], additional studies focusing on the combination therapy of senescence-related treatment with immunotherapy would be a promising strategy to augment clinical success in certain cancers.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive assessment of cellular senescence in the tumor microenvironment

Pei

Wang

et al. 2022

Briefings in Bioinformatics

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Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.

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“…The interaction between immune and metabolic process is termed as immunometabolism ( 41 ). The metabolic disorders of main nutrients (such as glucose, lipids and amino acids) in immune cells during aging lead to the dysregulation of nicotinamide adenine dinucleotide (NAD+) metabolism, activating inflammatory pathways and accelerating immunosenescence ( 42 ). With the increase of age, the level of glycolytic metabolism decreases and mitochondria energy metabolism is abnormal, which impairs T and B cell activation ( 43 , 44 ).…”

Section: The Role Of Aging-related Phenotypes In Immunosenescencementioning

confidence: 99%

Immunosenescence, aging and successful aging

Wang

Dong²,

Han³

et al. 2022

Front. Immunol.

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Aging induces a series of immune related changes, which is called immunosenescence, playing important roles in many age-related diseases, especially neurodegenerative diseases, tumors, cardiovascular diseases, autoimmune diseases and coronavirus disease 2019(COVID-19). However, the mechanism of immunosenescence, the association with aging and successful aging, and the effects on diseases are not revealed obviously. In order to provide theoretical basis for preventing or controlling diseases effectively and achieve successful aging, we conducted the review and found that changes of aging-related phenotypes, deterioration of immune organ function and alterations of immune cell subsets participated in the process of immunosenescence, which had great effects on the occurrence and development of age-related diseases.

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Metabolic regulation of immune cells in proinflammatory microenvironments and diseases during ageing

Cited by 13 publications

References 159 publications

Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis

Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis

Comprehensive assessment of cellular senescence in the tumor microenvironment

Immunosenescence, aging and successful aging

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