Metabolic Flexibility Determines Whether Cells Enter Reversible Quiescence or Irreversible Senescence

Cells that can switch between glucose and ketone metabolism resist senescence longer. When metabolic flexibility collapses—usually from mitochondrial dysfunction or NAD+ depletion—cells lose the capacity to enter quiescence and instead trigger permanent cell cycle arrest.

This suggests senescence is not just DNA damage response. It is metabolic commitment to a terminal state.