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Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in

Tapash Jay Sarkar1,2,3, Marco Quarta4,5,6,7, Shravani Mukherjee8

  • 1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Nature Communications
|March 27, 2020
PubMed

Insights

Transient expression of reprogramming factors via mRNA can reverse cellular aging in human cells. This approach resets epigenetic clocks and restores youthful function without altering cell identity.

Area of Science:

  • Gerontology
  • Epigenetics
  • Cellular Biology

Background:

  • Aging involves functional decline across all biological levels.
  • Epigenetic alterations accumulate with age, impacting gene regulation and cellular homeostasis.
  • Nuclear reprogramming can reverse cellular age and identity, but its effect on naturally aged human cells is unclear.

Purpose of the Study:

  • To investigate the effects of transient nuclear reprogramming on aged human cells.
  • To determine if reprogramming factors delivered via mRNA can rejuvenate human cells without identity loss.

Main Methods:

  • Transient expression of nuclear reprogramming factors using messenger RNA (mRNA).
  • Assessment of epigenetic clock resetting.
  • Analysis of inflammatory profiles in chondrocytes.
  • Evaluation of regenerative capacity in aged human muscle stem cells.

Main Results:

  • Rapid and broad amelioration of cellular aging markers observed.
  • Successful resetting of the epigenetic clock in human cells.
  • Reduced inflammatory profile in aged chondrocytes.
  • Restored youthful regenerative response in aged human muscle stem cells.
  • Cellular identity was preserved throughout the process.

Conclusions:

  • Transient mRNA-mediated reprogramming is a viable strategy for rejuvenating aged human cells.
  • This method effectively reverses key aging hallmarks, including epigenetic age and functional decline.
  • Rejuvenation is achieved without compromising the specialized identity of the cells, offering therapeutic potential.

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