Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis

Wiley, Christopher D.; Sharma, Rishi; Davis, Sonnet S.; López-Domínguez, José A; Mitchell, Kylie P.; Wiley, Samantha; Alimirah, Fatouma; Kim, Dong-Eun; Payne, Therese; Rosko, Andrew; Aimontche, Eliezer; Deshpande, Sharvari M.; Neri, Francesco; Kuehnemann, Chisaka; Demaria, Marco; Ramanathan, Arvind; Campisi, Judith

doi:10.1016/j.cmet.2021.03.008

Cited by 116 publications

(91 citation statements)

References 75 publications

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“…Exogenous lipids are preferentially incorporated into triacylglyerols, which form the lipid droplets in senescent cells 123 . Furthermore, free polyunsaturated fatty acid (PUFA) levels increase in senescent cells 124 , likely via p38-dependent activation of phospholipase A2, which cleaves PUFAs from cellular membranes 125 . Senescent cells incorporate higher levels of PUFAs into triglycerides 126 , which ultimately accumulate in lipid droplets.…”

Section: Lipid Metabolismmentioning

confidence: 99%

“…The release of free PUFAs from the plasma membrane is associated with multiple forms of senescence 124,126 . Additionally, levels of several PUFAs, such as eicosapentanoic acid (EPA), arachidonic acid (AA), dihomo-γ-linolenic acid (DGLA) and docosohexanoic acid (DHA), are highly elevated during MiDAS 124 , above other forms of senescence. This elevation may reflect an attempt by cells to preserve the NAD redox balance by using PUFA desaturation to convert NADH into NAD + , as described 128 .…”

Section: Lipid Metabolismmentioning

confidence: 99%

“…This elevation may reflect an attempt by cells to preserve the NAD redox balance by using PUFA desaturation to convert NADH into NAD + , as described 128 . Beyond accumulating as triglycerides in lipid droplets, free PUFAs are also converted to oxygenated signaling molecules collectively known as oxylipins 124 . Oxylipins associated with cellular senescence include leukotrienes 125,129 and prostaglandins, including dihomo-prostaglandins 124,130 .…”

Section: Lipid Metabolismmentioning

confidence: 99%

“…Beyond accumulating as triglycerides in lipid droplets, free PUFAs are also converted to oxygenated signaling molecules collectively known as oxylipins 124 . Oxylipins associated with cellular senescence include leukotrienes 125,129 and prostaglandins, including dihomo-prostaglandins 124,130 . Senescence-associated leukotriene release drives profibrotic features of pulmonary fibrosis, and eliminating senescent cells ameliorates these effects 125,131 .…”

Section: Lipid Metabolismmentioning

confidence: 99%

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The metabolic roots of senescence: mechanisms and opportunities for intervention

2021

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Cellular senescence entails a permanent proliferative arrest, coupled to multiple phenotypic changes. Among these changes is the release of numerous biologically active molecules collectively known as the senescence-associated secretory phenotype, or SASP. A growing body of literature indicates that both senescence and the SASP are sensitive to cellular and organismal metabolic states, which in turn can drive phenotypes associated with metabolic dysfunction. Here, we review the current literature linking senescence and metabolism, with an eye toward findings at the cellular level, including both metabolic inducers of senescence and alterations in cellular metabolism associated with senescence. Additionally, we consider how interventions that target either metabolism or senescent cells might influence each other and mitigate some of the pro-aging effects of cellular senescence. We conclude that the most effective interventions will likely break a degenerative feedback cycle by which cellular senescence promotes metabolic diseases, which in turn promote senescence.

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Section: Lipid Metabolismmentioning

confidence: 99%

Section: Lipid Metabolismmentioning

confidence: 99%

Section: Lipid Metabolismmentioning

confidence: 99%

Section: Lipid Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

The metabolic roots of senescence: mechanisms and opportunities for intervention

2021

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“…In the former case, the MIP reveals a receptor-like behavior, with preferred retention for structural analogs of the template. This is of interest for the future development of targeted extractions of specific PG biomarkers [ 39 ]. In contrast, the latter conditions offer an alternative procedure to the more established comprehensive profile of lipid mediators.…”

Section: Discussionmentioning

confidence: 99%

Tailored Polymer-Based Selective Extraction of Lipid Mediators from Biological Samples

et al. 2021

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Lipid mediators, small molecules involved in regulating inflammation and its resolution, are a class of lipids of wide interest as their levels in blood and tissues may be used to monitor health and disease states or the effect of new treatments. These molecules are present at low levels in biological samples, and an enrichment step is often needed for their detection. We describe a rapid and selective method that uses new low-cost molecularly imprinted (MIP) and non-imprinted (NIP) polymeric sorbents for the extraction of lipid mediators from plasma and tissue samples. The extraction process was carried out in solid-phase extraction (SPE) cartridges, manually packed with the sorbents. After extraction, lipid mediators were quantified by liquid chromatography–tandem mass spectrometry (LC–MSMS). Various parameters affecting the extraction efficiency were evaluated to achieve optimal recovery and to reduce non-specific interactions. Preliminary tests showed that MIPs, designed using the prostaglandin biosynthetic precursor arachidonic acid, could effectively enrich prostaglandins and structurally related molecules. However, for other lipid mediators, MIP and NIP displayed comparable recoveries. Under optimized conditions, the recoveries of synthetic standards ranged from 62% to 100%. This new extraction method was applied to the determination of the lipid mediators concentration in human plasma and mouse tissues and compared to other methods based on commercially available cartridges. In general, the methods showed comparable performances. In terms of structural specificity, our newly synthesized materials accomplished better retention of prostaglandins (PGs), hydroxydocosahexaenoic acid (HDoHE), HEPE, hydroxyeicosatetraenoic acids (HETE), hydroxyeicosatrienoic acid (HETrE), and PUFA compounds, while the commercially available Strata-X showed a higher recovery for dihydroxyeicosatetraenoic acid (diHETrEs). In summary, our results suggest that this new material can be successfully implemented for the extraction of lipid mediators from biological samples.

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Cellular senescence and the tumour microenvironment

2022

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The senescence‐associated secretory phenotype (SASP), where senescent cells produce a variety of secreted proteins including inflammatory cytokines, chemokines, matrix remodelling factors, growth factors and so on, plays pivotal but varying roles in the tumour microenvironment. The effects of SASP on the surrounding microenvironment depend on the cell type and process of cellular senescence induction, which is often associated with innate immunity. Via SASP‐mediated paracrine effects, senescent cells can remodel the surrounding tissues by modulating the character of adjacent cells, such as stromal, immune cells, as well as cancer cells. The SASP is associated with both tumour‐suppressive and tumour‐promoting effects, as observed in senescence surveillance effects (tumour‐suppressive) and suppression of anti‐tumour immunity in most senescent cancer‐associated fibroblasts and senescent T cells (tumour‐promoting). In this review, we discuss the features and roles of senescent cells in tumour microenvironment with emphasis on their context‐dependency that determines whether they promote or suppress cancer development. Potential usage of recently developed drugs that suppress the SASP (senomorphics) or selectively kill senescence cells (senolytics) in cancer therapy are also discussed.

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Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis

Cited by 116 publications

References 75 publications

The metabolic roots of senescence: mechanisms and opportunities for intervention

The metabolic roots of senescence: mechanisms and opportunities for intervention

Tailored Polymer-Based Selective Extraction of Lipid Mediators from Biological Samples

Cellular senescence and the tumour microenvironment

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