Genomic stability, anti-inflammatory phenotype, and up-regulation of the RNAseH2 in cells from centenarians
| Autor: | Silvia Latini, Francesco Fabbri, Manuela Ferracin, Anna Tesei, Sabrina De Carolis, Stefano Salvioli, Elena Marasco, Noémie Gensous, Fabiola Olivieri, Maria Giulia Bacalini, Chiara Arienti, Massimiliano Bonafè, Michele Zanoni, Gianluca Storci, Emanuela Mensà, Anna Sarnelli, Alessio Papi, Spartaco Santi, Claudio Franceschi, Paolo Garagnani |
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| Přispěvatelé: | Storci G., De Carolis S., Papi A., Bacalini M.G., Gensous N., Marasco E., Tesei A., Fabbri F., Arienti C., Zanoni M., Sarnelli A., Santi S., Olivieri F., Mensa E., Latini S., Ferracin M., Salvioli S., Garagnani P., Franceschi C., Bonafe M. |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine DNA repair DNA damage Longevity Ribonuclease H Breast Neoplasms Inflammation Biology Methylation Article Extracellular Vesicles Young Adult 03 medical and health sciences 0302 clinical medicine Interferon medicine Humans Molecular Biology Cellular Senescence Aged Aged 80 and over Interleukin-6 Telomere Homeostasis Interferon-beta Cell Biology Fibroblasts Middle Aged Phenotype Plaque Atherosclerotic DNA damage response centenarians RNA:DNA hybrids inflammation 3. Good health Telomere Cell biology Comet assay MicroRNAs 030104 developmental biology Genetic Loci 030220 oncology & carcinogenesis Cancer cell Female medicine.symptom DNA Damage medicine.drug |
| Zdroj: | Cell Death Differ Cell Death & Differentiation |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | Current literature agrees on the notion that efficient DNA repair favors longevity across evolution. The DNA damage response machinery activates inflammation and type I interferon signaling. Both pathways play an acknowledged role in the pathogenesis of a variety of age-related diseases and are expected to be detrimental for human longevity. Here, we report on the anti-inflammatory molecular make-up of centenarian’s fibroblasts (low levels of IL-6, type 1 interferon beta, and pro-inflammatory microRNAs), which is coupled with low level of DNA damage (measured by comet assay and histone-2AX activation) and preserved telomere length. In the same cells, high levels of the RNAseH2C enzyme subunit and low amounts of RNAseH2 substrates, i.e. cytoplasmic RNA:DNA hybrids are present. Moreover, RNAseH2C locus is hypo-methylated and RNAseH2C knock-down up-regulates IL-6 and type 1 interferon beta in centenarian’s fibroblasts. Interestingly, RNAseH2C locus is hyper-methylated in vitro senescent cells and in tissues from atherosclerotic plaques and breast tumors. Finally, extracellular vesicles from centenarian’s cells up-regulate RNAseH2C expression and dampen the pro-inflammatory phenotype of fibroblasts, myeloid, and cancer cells. These data suggest that centenarians are endowed with restrained DNA damage-induced inflammatory response, that may facilitate their escape from the deleterious effects of age-related chronic inflammation. |
| Databáze: | OpenAIRE |
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