Cardiolipin induces premature senescence in normal human fibroblasts

Arivazhagan, Palaniyappan; Mizutani, Emi; Fujii, Michihiko; Ayusawa, Dai

doi:10.1016/j.bbrc.2004.08.177

Cited by 19 publications

(8 citation statements)

References 20 publications

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“…Cardiolipin has been identified as a mitochondrial DAMP and has been demonstrated to promote inflammation when it becomes exposed in damaged mitochondria . In the context of senescence, it has been shown that there is an accumulation of cardiolipin in senescent cells and that exposure of human fibroblasts to cardiolipin can contribute to senescence . Another important mitochondrial‐derived DAMP is mtDNA.…”

Section: Mitochondrial Dysfunction Is a Feature Of Cellular Senescencementioning

confidence: 99%

Mitochondrial dysfunction and cell senescence: deciphering a complex relationship

2019

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Cellular senescence and mitochondrial dysfunction have both been defined as classical hallmarks of the ageing process. Here, we review the intricate relationship between the two. In the context of ageing, it is now well regarded that cellular senescence is a key driver in both ageing and the onset of a number of age‐related pathologies. Emerging evidence has pinpointed mitochondria as one of the key modulators in the development of the senescence phenotype, particularly the pro‐inflammatory senescence associated secretory phenotype (SASP). This review focuses on the contribution of homeostatic mechanisms, as well as of reactive oxygen species and mitochondrial metabolites in the senescence programme. Furthermore, we discuss emerging pathways and mitochondrial‐mediated mechanisms that may be influencing the SASP and, subsequently, explore how these may be exploited to open up new therapeutic avenues.

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Section: Mitochondrial Dysfunction Is a Feature Of Cellular Senescencementioning

confidence: 99%

Mitochondrial dysfunction and cell senescence: deciphering a complex relationship

2019

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“…1) Normal cells also show a similar phenomenon, termed "premature senescence," at any stages of culture by treatment with various agents such as reactive oxygen species, DNA damaging agents, lipids, cell cycle inhibitors, chromatin-destabilizing agents, and modulators of cell signaling 2,3) and cardiolipin. 4) Occasionally, tumor-derived immortal cell lines, which are thought to be escaped from senescence, show a senescence-like phenomenon by treatment with specific agents such as excess thymidine and 5-bromodeoxyuridine. [5][6][7] Morphological alterations and retardation of DNA replication are always coupled with replicative senescence, premature senescence, and various forms of cellular senescence-like phenomena.…”

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confidence: 99%

Molecular basis for premature senescence induced by surfactants in normal human cells

Yamakami

Miki

Yonekura

et al. 2014

Bioscience, Biotechnology, and Biochemistry

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Sublethal doses of surfactants as exemplified by NP-40 clearly induce premature senescence in normal human cells. To understand molecular basis for this phenomenon, we tried to suppress it with use of various inhibitors. An inhibitor of p38 of the MAPK family almost completely suppressed growth arrest and morphological changes induced by surfactants; however, other inhibitors tested had no effect. Oleic acid, a weak inducer of premature senescence, was found to suppress the effect of NP-40. Fluorescein-labeled oleic acid rapidly bound to the cell surface, and this binding was clearly blocked by pre-treatment with surfactants, suggesting that surfactants and oleic acid compete for binding to the cell surface. Moderate concentrations of cycloheximide, an inhibitor of protein synthesis, also suppressed the senescent features induced by NP-40. These results suggest that surfactants activate p38 signaling pathway by binding to the cell surface, and induce cellular senescence.

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“…2). These morphological changes were quite similar to normal mitotic cells in replicative or premature senescence stage (Arivazhagan et al 2004) and to HeLa cells induced to enter the ''senescence like'' phenomenon, by BrdU (Michishita et al 1999).…”

Section: Induction Of Senescence Markersmentioning

confidence: 94%

Cyclophosphamide induces premature senescence in normal human fibroblasts by activating MAP kinases

Arivazhagan

2009

Biogerontology

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Cellular senescence is induced by diverse mechanisms and is in turn mediated by multiple biochemical pathways. We found that cyclophosphamide sensitively inhibits the growth of normal human fibroblasts. Those growth arrested fibroblasts showed morphology similar to that of normally senesced cells and strongly expressed senescence-associated β-galactosidase. They also showed up regulation of senescence-associated genes and eventually lost their division potential. In addition, enhanced phosphorylation of MAP kinases was found in growth arrested cells, very similar to normally senesced cells. Collectively, these results suggest that cyclophosphamide uses signaling pathways similar to those that are active in replicative senescence, thereby leading to premature senescence.

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Cardiolipin induces premature senescence in normal human fibroblasts

Cited by 19 publications

References 20 publications

Mitochondrial dysfunction and cell senescence: deciphering a complex relationship

Mitochondrial dysfunction and cell senescence: deciphering a complex relationship

Molecular basis for premature senescence induced by surfactants in normal human cells

Cyclophosphamide induces premature senescence in normal human fibroblasts by activating MAP kinases

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