Cell Differentiation and Aging Lead To Up-Regulation of FTO, While the ALKBH5 Protein Level Was Stable During Aging but Up-Regulated During in vitro-Induced Cardiomyogenesis

Oct 5, 2023Physiological research

Cell Development and Aging Increase FTO Levels, While ALKBH5 Stays Stable with Age but Rises During Lab-Induced Heart Cell Formation

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Abstract

Aging in male and female mice is associated with FTO up-regulation in multiple organs.

  • FTO and ALKBH5 proteins are crucial for removing N6-adenosine methylation from RNA.
  • FTO levels increased during aging in the hearts, brains, lungs, and kidneys of mice, while ALKBH5 levels remained stable.
  • Both proteins were elevated during cardiomyogenesis, but ALKBH5 levels did not change during neuroectodermal differentiation.
  • Depleting HDAC1 in mouse embryonic stem cells led to a decrease in FTO levels.
  • In these stem cells, specific gene loci showed reduced N6-adenosine methylation that influences cell differentiation into neuroectoderm.
  • FTO appears to have a more significant role than ALKBH5 in regulating m6A RNA demethylation during aging and neuronal differentiation.

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