sirtuin-activating compound
{{short description|Chemical compounds having an effect on sirtuins}}
Sirtuin-activating compounds (STAC) are chemical compounds having an effect on sirtuins, a group of enzymes that use NAD+ to remove acetyl groups from proteins. They are caloric restriction mimetic compounds that may be helpful in treating various aging-related diseases.{{Cite journal
| last1 = Gan | first1 = L.
| title = Therapeutic potential of sirtuin-activating compounds in Alzheimer's disease
| doi = 10.1358/dnp.2007.20.4.1101162
| journal = Drug News & Perspectives
| volume = 20
| issue = 4
| pages = 233–239
| year = 2007
| pmid = 17637936
}}
Context
Leonard P. Guarente is recognized as the leading proponent of the hypothesis that caloric restriction slows aging by activation of Sirtuins.{{cn|date=November 2024}}
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 polyphenols such as resveratrol{{Cite journal | last1 = Kaeberlein | first1 = M. | last2 = McDonagh | first2 = T. | last3 = Heltweg | first3 = B. | last4 = Hixon | first4 = J. | last5 = Westman | first5 = E. A. | last6 = Caldwell | first6 = S. D. | last7 = Napper | first7 = A. | last8 = Curtis | first8 = R. | last9 = Distefano | first9 = P. S. | last10 = Fields | first10 = S. | last11 = Bedalov | first11 = A. | last12 = Kennedy | first12 = B. K. | title = Substrate-specific Activation of Sirtuins by Resveratrol | doi = 10.1074/jbc.M500655200 | journal = Journal of Biological Chemistry | volume = 280 | issue = 17 | pages = 17038–17045 | year = 2005 | pmid = 15684413| doi-access = free }} activate human SIRT1 and extend the lifespan of budding yeast (Howitz et al., Nature, 2003). Other examples of such products are butein, piceatannol, isoliquiritigenin, fisetin, and quercetin.{{cn|date=November 2024}}
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.{{Cite web|title=What is NMN?|url=https://www.nmn.com/precursors/what-is-nmn|access-date=2021-01-08|website=www.nmn.com}}
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.{{cite journal|last1=Lakshminarasimhan|first1=M|last2=Rauh|first2=D|last3=Schutkowski|first3=M|last4=Steegborn|first4=C|title=Sirt1 activation by resveratrol is substrate sequence-selective|journal=Aging|volume=5|pages=151–4|pmid=23524286|issue=3|date=Mar 2013|doi=10.18632/aging.100542|pmc=3629287}}{{cite journal|last1=Hubbard|first1=BP|title=Evidence for a common mechanism of SIRT1 regulation by allosteric activators|journal=Science|volume=339|pages=1216–9|pmid=23471411|doi=10.1126/science.1231097|issue=6124|date=Mar 2013|display-authors=etal|pmc=3799917}}
Sirtris Pharmaceuticals, Sinclair's company, was purchased by GlaxoSmithKline (GSK) in 2008, and subsequently shut down as a separate entity within GSK.{{cn|date=November 2024}}
See also
References
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External links
- http://pubs.acs.org/cen/coverstory/8234/8234aging.html
- [http://www.wipo.int/pctdb/en/wo.jsp?wo=2006078941 Sirtris Pharmaceuticals' US patent for STAC]
- [http://www.faqs.org/patents/app/20080255382 Patent title: Novel Sirtuin Activating Compounds and Methods for Making the Same]