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The dark side of circulating nucleic acids.

Silvia Gravina1, John M Sedivy2, Jan Vijg1

  • 1Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

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Cell-free DNA (cfDNA) in the bloodstream may cause DNA mutations and cellular aging. This process could contribute to age-related diseases like cancer and Alzheimer's.

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DNA damageagingcell-free DNAmutagenesis

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Cell-free DNA (cfDNA) is DNA circulating in the bloodstream, originating from dying cells.
  • cfDNA is of significant interest for noninvasive diagnostic applications.
  • Previous studies showed that cfDNA can be taken up by cells.

Purpose of the Study:

  • To investigate the effects of cfDNA uptake on host cells.
  • To explore the potential role of cfDNA in cellular aging and disease.

Main Methods:

  • In vitro and in vivo experiments involving cfDNA uptake by mouse cells.
  • Analysis of cellular responses, including DNA damage response (DDR) and apoptosis markers.

Main Results:

  • Uptake of human cfDNA by mouse cells was observed.
  • cfDNA uptake triggered a DNA damage response (DDR) in host cells.
  • Apoptotic proteins appeared in host cells following cfDNA uptake.

Conclusions:

  • cfDNA can act as a source of mobile genetic elements within the body.
  • Continuous exposure to cfDNA may lead to DNA mutagenesis and cellular aging.
  • cfDNA might be a causal factor in aging-related diseases such as cancer, diabetes, and Alzheimer's disease.