Plant Polyphenols that are Sirtuin-activating compounds (STACs)


Sirtuin or Sir2 proteins are a class of proteins that regulate important biological pathways in humans.

Sirtuins regulate a variety of cellular processes, such as:

  • aging
  • apoptosis
  • circadian clocks
  • inflammation
  • mitochondrial biogenesis
  • stress resistance
  • transcription

Scientists have identified seven (7) sirtuins in humans that demonstrate different metabolic functions.  These 7 sirtuins are listed as SIRT1 to SIRT7.

SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 and is an enzyme that deacetylates proteins that contribute to cellular regulation, such as reactions to stressors and longevity.

In 2003 Konrad Howitz and David Sinclair discovered that polyphenols such as resveratrol activate human SIRT1 and extend the lifespan of budding yeast.  They publsihed their findings in the September 2003 edition of the Journal Nature entitled,  Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan,  Nature 425, 191-196 (11 September 2003) | doi:10.1038/nature01960.  

Howitz and Sinclair coined the term STAC which stands for Sirtuin-activating compounds, which are chemical compounds having an effect on sirtuins.

Since 2003, other polyphenols compounds have been discovered to be STACs.  These sirtuin-activating compounds (STACs) include:   1

  • Butein
  • Fisetin
  • Isoliquiritigenin
  • Piceatannol
  • Quercetin
  • Resveratrol

Butein is a active compound from the stems of Rhus verniciflua Stokes. It has been used for centuries in Traditional Chinese Medicine.  Butein has been shown to be an aromatase inhibitor and a potential natural alternative for the chemoprevention or therapy of breast cancer.  2

Fisetin is a compound that is found in strawberries and other fruits and vegetables.  It is being investigated for its neurological benefits.  Research data demonstrates that fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders.  3

Isoliquiritigenin is a licorice chalconoid, and is found in herbal medicines such as licorice (Glycyrrhiza uralensis Fisher).   4 

Piceatannol, a naturally occurring analog of resveratrol, is considered to be a promising chemopreventive or anticancer agent.  5  Piceatannol is a closely related stilbene that has antileukaemic activity and is also a tyrosine kinase inhibitor.  Resveratrol undergoes metabolism by the cytochrome P450 enzyme CYP1B1 to give a metabolite which has been identified as the known antileukaemic agent piceatannol.  6

Quercetin is is a polyphenol that is found in many foods, such as capers, lovage, apples, tea, onions, citrus fruits, green vegetables and most berries. Quercetin has been demonstrated to be protective against several chronic diseases.  7

Resveratrol is found in raspberries, blueberries, grapeskins, peanuts, Japanese Knotweed and some pine trees. Resveratrol has been shown to have a wide range of biological effects, including anti-platelet, anti-inflammatory, anti-cancer, anti-mutagenic and protection from atherosclerotic disease.


Butein – No known extract or supplement available.

Fisetin (Novusetin™ Fisetin)





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