Nuclear DNA damage signalling to mitochondria in ageing

Nat Rev Mol Cell Biol. 2016 May;17(5):308-21. doi: 10.1038/nrm.2016.14. Epub 2016 Mar 9.


Mitochondrial dysfunction is a hallmark of ageing, and mitochondrial maintenance may lead to increased healthspan. Emerging evidence suggests a crucial role for signalling from the nucleus to mitochondria (NM signalling) in regulating mitochondrial function and ageing. An important initiator of NM signalling is nuclear DNA damage, which accumulates with age and may contribute to the development of age-associated diseases. DNA damage-dependent NM signalling constitutes a network that includes nuclear sirtuins and controls genomic stability and mitochondrial integrity. Pharmacological modulation of NM signalling is a promising novel approach for the prevention and treatment of age-associated diseases.

Publication types

  • Review

MeSH terms

  • Aging*
  • Animals
  • Apoptosis
  • Cell Nucleus / genetics
  • DNA Damage*
  • DNA Repair
  • Genomic Instability
  • Humans
  • Mitochondria / physiology*
  • Mitophagy
  • Reactive Oxygen Species / metabolism
  • Signal Transduction


  • Reactive Oxygen Species