Markers of Aging in Cells of Patients with Cockayne Syndrome. General and Individual Differences

Slizhov, Pavel; Dolinina, T. I.; Pleskach, Nadezhda; Василишина, А. А.; Zherebtsov, Sergey; Bulatnikova, M.A.; Mikhelson, V. M.; Spivak, I. M.

doi:10.1134/s1990519x18040090

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…To determine whether IR induces cellular senescence in mIMCD-3 cells, cell viability and senescence-associated markers, HP1γ and SIRT1 (19), were initially measured. Cell viability and the proportion of cells in G1 phase of the cell cycle were significantly decreased in mIMCD-3 cells in response to irradiation (Fig.…”

Section: Radiation Induces Senescence Of Kidney Cellsmentioning

confidence: 99%

Involvement of Klotho, TNF‑α and ADAMs in radiation‑induced senescence of renal epithelial cells

2020

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While radiation nephropathy is a major problem associated with radiotherapy, the exact mechanisms underlying its pathogenesis and the mediators involved in kidney deterioration remain to be elucidated. In view of the finding that senescence is typically increased post-irradiation, the present study examined whether ionizing radiation may cause kidney injury by enhancing premature senescence. The present study explored the relevance of the aging suppressor, Klotho, which has anti-aging activity and is highly expressed in murine renal cells/kidney tissues, under irradiation conditions. Firstly, the effects of radiation on mouse inner medullary collecting duct-3 (mIMCD-3) cells and kidney tissues of mice were assessed. Subsequently, the mRNA expression levels of Klotho, TNF-α and ADAM metallopeptidase domain (ADAM)9/10/17 were analyzed by reverse transcription-quantitative PCR following exposure to radiation. In addition, the levels of these proteins were measured by western blotting or ELISA. The results revealed that irradiation of mIMCD-3 cells clearly triggered cellular senescence. Notably, Klotho gene expression was considerably decreased in radiation-exposed mIMCD-3 cells and in the kidney tissues of irradiated BALB/c mice, and the corresponding translated protein was consistently expressed following radiation exposure. Moreover, expression of TNF-α, a negative regulator of Klotho, was significantly increased, whereas ADAM9/10/17, an ectodomain shedding enzyme of Klotho, was decreased in irradiated mIMCD-3 cells and in the kidney tissues of BALB/c mice. Collectively, these data suggested that TNF-α-mediated inhibition of Klotho expression and blockage of soluble Klotho formation via decreased ADAM expression following irradiation may contribute to the development of renal dysfunction through acceleration of radiation-induced cellular senescence.

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Section: Radiation Induces Senescence Of Kidney Cellsmentioning

confidence: 99%

Involvement of Klotho, TNF‑α and ADAMs in radiation‑induced senescence of renal epithelial cells

2020

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PML Nuclear Bodies and Cellular Senescence: A Comparative Study of Healthy and Premature Aging Syndrome Donors’ Cells

Smirnov,

Silonov,

Shmidt

et al. 2024

Cells

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Natural aging and age-related diseases involve the acceleration of replicative aging, or senescence. Multiple proteins are known to participate in these processes, including the promyelocytic leukemia (PML) protein, which serves as a core component of nuclear-membrane-less organelles known as PML nuclear bodies (PML-NBs). In this work, morphological changes in PML-NBs and alterations in PML protein localization at the transition of primary fibroblasts to a replicative senescent state were studied by immunofluorescence. The fibroblasts were obtained from both healthy donors and donors with premature aging syndromes (ataxia-telangiectasia and Cockayne syndrome). Our data showed an increase in both the size and the number of PML-NBs, along with nuclear enlargement in senescent cells, suggesting these changes could serve as potential cellular aging markers. Bioinformatic analysis demonstrated that 30% of the proteins in the PML interactome and ~45% of the proteins in the PML-NB predicted proteome are directly associated with senescence and aging processes. These proteins are hypothesized to participate in post-translational modifications and protein sequestration within PML-NBs, thereby influencing transcription factor regulation, DNA damage response, and negative regulation of apoptosis. The findings confirm the significant role of PML-NBs in cellular aging processes and open new avenues for investigating senescence mechanisms and age-associated diseases.

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Markers of Aging in Cells of Patients with Cockayne Syndrome. General and Individual Differences

Cited by 2 publications

References 42 publications

Involvement of Klotho, TNF‑α and ADAMs in radiation‑induced senescence of renal epithelial cells

Involvement of Klotho, TNF‑α and ADAMs in radiation‑induced senescence of renal epithelial cells

PML Nuclear Bodies and Cellular Senescence: A Comparative Study of Healthy and Premature Aging Syndrome Donors’ Cells

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Markers of Aging in Cells of Patients with Cockayne Syndrome. General and Individual Differences

Cited by 2 publications

References 42 publications

Involvement of Klotho, TNF‑&alpha; and ADAMs in radiation‑induced senescence of renal epithelial cells

Involvement of Klotho, TNF‑&alpha; and ADAMs in radiation‑induced senescence of renal epithelial cells

PML Nuclear Bodies and Cellular Senescence: A Comparative Study of Healthy and Premature Aging Syndrome Donors’ Cells

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Product

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Involvement of Klotho, TNF‑α and ADAMs in radiation‑induced senescence of renal epithelial cells

Involvement of Klotho, TNF‑α and ADAMs in radiation‑induced senescence of renal epithelial cells