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Updated: Apr 17, 2026

In Vitro Modeling of Down Syndrome Neurogenesis Using Human-Induced Pluripotent Stem Cells
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Accelerated epigenetic aging in Down syndrome.

Steve Horvath1, Paolo Garagnani, Maria Giulia Bacalini

  • 1Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA; Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA.

Aging Cell
|February 14, 2015
PubMed
Summary
This summary is machine-generated.

Down Syndrome (trisomy 21) accelerates biological aging. Molecular epigenetic clocks show trisomy 21 significantly increases the biological age of blood and brain tissues, suggesting earlier onset of age-related diseases.

Keywords:
DNA methylationDown syndromebiomarker of agingepigenetics

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Area of Science:

  • Genetics and Molecular Biology
  • Aging Research
  • Developmental Biology

Background:

  • Down Syndrome (DS) is associated with an elevated risk of chronic diseases typically seen in older individuals.
  • Clinical observations suggest trisomy 21 may accelerate biological aging at the tissue level.
  • Molecular evidence supporting accelerated aging in DS has been limited.

Purpose of the Study:

  • To investigate whether trisomy 21 impacts biological age at a molecular level.
  • To quantify the effect of trisomy 21 on the epigenetic aging of specific tissues.

Main Methods:

  • Utilized a quantitative molecular marker of aging, the epigenetic clock.
  • Analyzed blood and brain tissue samples.

Main Results:

  • Demonstrated that trisomy 21 significantly increases biological age.
  • Epigenetic age of blood and brain tissue was found to be, on average, 6.6 years older in individuals with trisomy 21 (P = 7.0 × 10(-14)).

Conclusions:

  • Trisomy 21 accelerates biological aging in blood and brain tissues.
  • These findings provide molecular evidence for the accelerated aging hypothesis in Down Syndrome.
  • This could have implications for understanding and managing age-related diseases in DS.