GRSF1 is an age-related regulator of senescence

Sci Rep. 2019 Apr 3;9(1):5546. doi: 10.1038/s41598-019-42064-6.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • DNA Methylation
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology
  • Poly(A)-Binding Proteins / genetics*
  • Poly(A)-Binding Proteins / metabolism
  • Promoter Regions, Genetic

Substances

  • GRSF1 protein, human
  • Grsf1 protein, mouse
  • Poly(A)-Binding Proteins