文章基本信息

标题：GRSF1 is an age-related regulator of senescence
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作者：Su-Jeong Kim ; Maria Chun ; Junxiang Wan 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-9
DOI：10.1038/s41598-019-42064-6
出版社：Springer Nature
摘要：Senescent cells that accumulate in multiple tissues with age are thought to increase pathological phenotypes. The removal of senescent cells can improve lifespan and/or healthspan in mouse models. Global hypomethylation and local hypermethylation in DNA are hallmarks of aging but it is unclear if such age-dependent methylation changes affect specific genes that regulate cellular senescence. Because mitochondria play important roles in aging and senescence, we tested if age-associated methylation changes in nuclear-encoded mitochondrial proteins were involved in regulating cellular senescence. Here, we examined the role of hypermethylation of the G-rich sequence factor 1 (GRSF1) promoter region, a mitochondrial RNA binding protein, in replication- and doxorubicin-induced cellular senescence. GRSF1 expression was lower in senescent fibroblasts, and GRSF1 knockdown induced senescence in human primary fibroblasts. These results suggest that the age-dependent hypermethylation of GRSF1 reduces its expression, which can potentially contribute to cellular senescence during aging.