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Updated: Aug 30, 2025

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S6 kinase 1 at the central node of cell size and ageing

Stefano Fumagalli1, Mario Pende1

  • 1Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Paris, France.

Frontiers in Cell and Developmental Biology
|August 29, 2022
PubMed

Insights

The Target Of Rapamycin (TOR) pathway, particularly p70 S6 kinase 1 (S6K1), is a master regulator of cell growth. S6K1 primarily controls cell size rather than proliferation, impacting aging and regeneration.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The Target Of Rapamycin (TOR) kinase pathway is a crucial regulator of growth in eukaryotes.
  • p70 S6 kinase 1 (S6K1) is a key downstream target of mTOR, sensitive to nutrients and rapamycin.
  • In vivo studies indicate S6K1's predominant role in regulating cell size over proliferation.

Purpose of the Study:

  • To review the mechanisms by which S6K1 influences cell size.
  • To explore the functional categories of S6K1 targets involved in cell size regulation.
  • To discuss the connection between S6K1, cell size, regeneration, and aging.

Main Methods:

  • Literature review of genetic evidence from model organisms (yeast, plants, animals, humans).
  • Analysis of in vivo studies on mutant flies and mice.
  • Examination of S6K1 targets related to synthesis, metabolism, insulin signaling, senescence, and cytoskeleton.

Main Results:

  • S6K1 activation is highly sensitive to nutrient availability and rapamycin.
  • S6K1 predominantly controls cell size in vivo.
  • Identified S6K1 targets span nucleic acid/protein synthesis, fat accumulation, insulin signaling, senescence, and cytoskeleton organization.

Conclusions:

  • S6K1 plays a central role in regulating cell size through diverse molecular mechanisms.
  • The findings suggest a link between S6K1-mediated cell size control and cellular responses to aging and regeneration.
Keywords:
ageinggrowthmTORnutritionsenescencesignal transduction

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