• Introduction.
  • Sirtuins and Gene Silencing.
  • Sirtuins Activity.
  • Sirtuins and Senescence.


  • Silent information regulator (SIR).
  • Crossroads of nutrient sensing and stress regulation.
    • Responds to energy and nutrients.
    • Controls cellular health.
  • Regulates adaptive response to energy availability.
    • Silences genes.
    • Repairs DNA.
  • Senses biological stress in the environment.
    • DNA damage, change in temperature, a lack of nutrients.
  • Activity driven by multiple factors.
    • NAD+, polyphenols, quality and quantity of nutrients.
  • May play a role in health or lifespan extension.
    • Potentially mediates positive effects of fasting / caloric restriction.
    • Debate around relevant studies / confounding factors.

Sirtuins Affect Many Pathways

  • Involved in many regulatory functions, including:
    • Metabolism.
    • Inflammation.
    • Genome stability.
    • Cell cycle.
    • Insulin secretion.
    • Fatty acid oxidation.
  • Plays a role in:
    • Promoting insulin sensitivity.
    • Modulating circadian rhythms.
    • Improving genome stability.
    • Suppressing tumors.
    • Reducing inflammation.
    • Protecting against neurodegenerative diseases.
    • Controlling anxiety.

Sirtuins and Gene Silencing

  • Controls which genes to turn on and off during adversity.
    • Evolved for survival during adversity.
  • Silences genes by removing acetyl groups from histones.
    • Histones are DNA-protein complexes that the DNA inside every cell is wound up in. (see “The Epigenetics Revolution“)
    • When histones have an acetyl group, DNA can be transcribed.
    • When the acetyl group is removed, gene expression stops.

Sirtuins Activity

  • NAD+
    • NAD+ plays a key role in metabolism.
      • NAD+ involved in turning nutrients into energy (see “NAD” write-up).
    • Sirtuins can only remove acetyl groups in the presence of NAD+.
    • Sirtuins “consume” NAD+.
      • Unlike redox reactions, no NADH is formed, so there is no “cycling”.
      • Sirtuins “cleave” NAD+ to form nicotinamide (NAM, a form of vitamin B3).
      • NAM switches off sirtuins (negative feedback loop).
      • NAM has to be recycled to reform NAD+, or removed.
  • Polyphenols.
    • Reveratrol (subject to debate).
    • Pterostilbene.
      • Found in blueberries.
  • Nutrients.
    • Changes in nutrient availability or quality affect sirtuin activity.

Sirtuins and Senescence

  • Loss of the mitochondrial sirtuins can induce a senescence response.
  • Low NAD+/NADH ratios promote cellular senescence at least in part by limiting glycolysis and ATP production.

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