Sirtuin-activating compounds (STAC) are chemical compounds having an effect on

sirtuin Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins ...

s, a group of enzymes that use NAD+ to remove acetyl groups from proteins. They are

caloric restriction mimetic Calorie restriction mimetics (CRM), also known as energy restriction mimetics, are a hypothetical class of dietary supplements or drug candidates that would, in principle, mimic the substantial anti-aging effects that calorie restriction (CR) has o ...

compounds that may be helpful in treating various

aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...

-related diseases.

Context

Leonard P. Guarente Leonard Pershing Guarente (born 1952) is an American biologist best known for his research on life span extension in the budding yeast ''Saccharomyces cerevisiae'', roundworms (''Caenorhabditis elegans''), and mice. He is a Novartis Professor o ...

is recognized as the leading proponent of the hypothesis that caloric restriction slows aging by activation of Sirtuins. STACs have been discovered by Konrad Howitz of Biomol Inc and biologist David Sinclair. In September 2003, Howitz and Sinclair et al. published a highly cited paper reporting that

polyphenol Polyphenols () are a large family of naturally occurring organic compounds characterized by multiples of phenol units. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some o ...

s such as

resveratrol Resveratrol (3,5,4′-trihydroxy-''trans''-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources ...

activate human

SIRT1 Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 ('' S. cerevisiae''), referring to the fact ...

and extend the lifespan of budding yeast (Howitz et al., Nature, 2003). Other examples of such products are

butein Butein is a chalcone of the chalconoids. It can be found in '' Toxicodendron vernicifluum'' (or formerly ''Rhus verniciflua''), '' Dahlia'', ''Butea'' (''Butea monosperma'') and '' Coreopsis'' It has antioxidative Antioxidants are Chemical com ...

, piceatannol,

isoliquiritigenin Isoliquiritigenin is a phenolic chemical compound found in licorice. Metabolism The enzyme 6'-deoxychalcone synthase uses malonyl-CoA, 4-coumaroyl-CoA, NADPH, and H+ to produce CoA, isoliquiritigenin, CO2, NADP+, and H2O. The enzyme isoliquiri ...

fisetin Fisetin (7,3′,4′- flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It can be found in many plants, where it serves as a yellow/ochre colouring agent. It is also found in many fruits and vegetables, such as strawberries, ...

, and

quercetin Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor ...

. Sirtuins depend on the crucial cellular molecule called nicotinamide adenine dinucleotide (NAD+) for their function. Falling NAD+ levels during aging may adversely impact sirtuin maintenance of DNA integrity and ability to combat oxidative stress-induced cell damage. Increasing cellular NAD+ levels with supplements like nicotinamide mononucleotide (NMN) during aging may slow or reverse certain aging processes with sirtuin function enhancement. Some STACs can cause artificial effects in the assay initially used for their identification, but it has been shown that STACs also activate SIRT1 against regular polypeptide substrates, with an influence of the substrate sequence.

Sirtris Pharmaceuticals Sirtris Pharmaceuticals, Inc. was a biotechnology company based in Cambridge, MA that developed therapies for type 2 diabetes, cancer, and other diseases. Conceived in 2004 by Harvard University biologist David Sinclair and serial entrepreneur And ...

, Sinclair's company, was purchased by

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British Multinational corporation, multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a Mergers and acquisitions, merger of Gl ...

(GSK) in 2008, and subsequently shut down as a separate entity within GSK.

References

External links

* http://pubs.acs.org/cen/coverstory/8234/8234aging.html
Sirtris Pharmaceuticals' US patent for STAC

Patent title: Novel Sirtuin Activating Compounds and Methods for Making the Same

Context

References

External links

See also