2018
DOI: 10.1111/acel.12780
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Abstract: SummaryThe selective depletion of senescent cells (SCs) by small molecules, termed senolytic agents, is a promising therapeutic approach for treating age‐related diseases and chemotherapy‐ and radiotherapy‐induced side effects. Piperlongumine (PL) was recently identified as a novel senolytic agent. However, its mechanism of action and molecular targets in SCs was unknown and thus was investigated. Specifically, we used a PL‐based chemical probe to pull‐down PL‐binding proteins from live cells and then mass spe… Show more

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Cited by 98 publications
(79 citation statements)
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References 39 publications
(82 reference statements)
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“…Briefly, low-passage WI38 cells (<25 passages), IMR90 cells (<25 passages), RECs (<10 passages), and PACs (<4 passages) were used as NCs or for the induction of senescence. To induce SCs by ionizing radiation (IR-SCs), WI38, and IMR90 fibroblasts, RECs and PACs were treated as previously described [12][13][14]16 . To induce replicative senescence (RE-SCs), WI38 cells were subcultured until they stopped to divide and became permanently growth arrested or senescent after about 37 passages.…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…Briefly, low-passage WI38 cells (<25 passages), IMR90 cells (<25 passages), RECs (<10 passages), and PACs (<4 passages) were used as NCs or for the induction of senescence. To induce SCs by ionizing radiation (IR-SCs), WI38, and IMR90 fibroblasts, RECs and PACs were treated as previously described [12][13][14]16 . To induce replicative senescence (RE-SCs), WI38 cells were subcultured until they stopped to divide and became permanently growth arrested or senescent after about 37 passages.…”
Section: Methodsmentioning
confidence: 99%
“…To date, several classes of senolytics have been identified. These agents include natural compounds such as quercetin 8,9 , fisetin 10,11 , piperlongumine 12,13 , and curcumin analogs 14 ; and targeted therapeutics such as dasatinib (a nonspecific tyrosine kinase inhibitor) 8,15 , inhibitors of the antiapoptotic Bcl-2 family proteins [16][17][18] , an inhibitor of HSP90 and a histone deacetylase 19 , UBX101 (an inhibitor of the MDM2/p53 protein interaction) 20 ; and a modified FOXO4-p53 interfering peptide 21 . In addition, cytotoxic agents encapsulated with β(1,4)galacto-oligosaccharides have also been used to target SCs that have high levels of lysosomal β-galactosidase activity 22 .…”
mentioning
confidence: 99%
“…In an idiopathic pulmonary fibrosis model, mammalian target of rapamycin/peroxisome proliferator-activated receptor-γ complex 1α/β (mTOR/PGC-1α/β) axis is markedly upregulated in senescent lung epithelial cells [198]. Despite significant function of PGC-1α in mitochondrial biogenesis and senescence, only very few studies are found on its role in the retina, though some studies on its role in biogenesis exist [204,205]. It has been also demonstrated that PGC-1α-deficient mice developed some abnormalities in RPE cells that were associated with their accelerated senescence [200,206,207].…”
Section: Mitochondrial Biogenesis and Senescencementioning
confidence: 99%
“…In a p16-3MR transgenic mouse model, selective depletion of senescent cells by the small-molecule chemical UBX0101 reduced the development of posttraumatic osteoarthritis by creating a proregenerative microenvironment [226]. Piperlongumine (PL) is a biologically active alkaloid and a recently identified senolytic agent which can selectively kill senescent cells by targeting oxidation resistance 1 (OXR1) to mediate PL senolytic activity [205]. The multicenter Intervention Testing Program by the National Institute for Aging has identified five drugs that increase lifespan in genetically heterogenous mice, including rapamycin, acarbose, nordihydroguaiaretic acid, 17-α-oestradiol, and aspirin [227].…”
Section: Senolytic Drugs For Targeting Senescent Cellsmentioning
confidence: 99%
“…In the past few years, several therapeutic strategies have emerged to target senescent cells for delaying the aging process and preventing the progression of chronic diseases (2,5,28,65). Recent studies have identified dasatinib plus quercetin (85), heat shock protein 90 (HSP90) inhibitors (18), fisetin (86), mouse double minute 2 homolog antagonists (82) and agents acting on oxidation resistance protein 1 (87), and B-cell lymphoma 2 (8) as a potential senolytic agents that could extend health span and/or lifespan. Research efforts that identify novel gene targets, which regulate aging processes in model organisms (30,47), also provide a potentially valuable approach for drug repurposing (13) to improve outcomes in elderly patients suffering from age-related chronic diseases.…”
Section: Advances In Pharmacological Therapies To Delay Agingmentioning
confidence: 99%