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Synchrony and asynchrony between an epigenetic clock and developmental timing.

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Epigenetic aging, measured by DNA methylation clocks, begins in fetal retina and progresses normally in vitro. This aging is accelerated in Down syndrome, offering insights into developmental mechanisms.

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Area of Science:

  • Developmental Biology
  • Epigenetics
  • Chronological Age Estimation

Background:

  • Epigenetic changes are used to estimate chronological age.
  • Epigenetic aging clocks may operate during development.
  • The mammalian neural retina offers a model for studying developmental timing.

Purpose of the Study:

  • To investigate the relationship between developmental stage and epigenetic age.
  • To determine if epigenetic aging occurs in fetal tissues.
  • To explore epigenetic aging in Down syndrome.

Main Methods:

  • Utilized the mammalian neural retina for its regular developmental sequence.
  • Applied a DNA methylation-based epigenetic aging clock.
  • Examined fetal retina, in vitro cultures, and stem cell-derived retinal organoids.

Main Results:

  • Epigenetic age of fetal retina strongly correlates with chronological age.
  • Epigenetic aging progresses normally in vitro and in retinal organoids.
  • Epigenetic aging is accelerated in Down syndrome retinal organoids.

Conclusions:

  • Epigenetic aging starts in early fetal tissues, a few weeks post-conception.
  • Epigenetic aging is an intrinsic property of tissues.
  • Developing organs provide a platform for studying epigenetic aging mechanisms.