Sirtuin

Sirtuin is a class of enzyme, specifically NAD-dependent histone deacetylases (class 3), found in both prokaryotes and eukaryotes. They have been known to affect cellular metabolism through selective gene expression in eukaryotes (plants and animals). The name comes from silent mating type information regulation two^[1], the gene responsible for cellular regulation in yeast.

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Sirtuins in organisms

Sirtuins in lower eukaryotes

In yeast, roundworms, and fruitflies^[2], sir2 is the name of the sirtuin-type enzyme. This research started in 1991 by Leonard Guarente of Harvard Medical School ^[3][4].

Sirtuins as possible agents in retardation of the aging process

Sirtuins may be able to control age-related disorders in various organisms and in humans. These disorders include the aging process, obesity, metabolic syndrome, type II diabetes mellitus^[5] and Parkinson's disease. Normally, sirtuin activity is inhibited by nicotinamide, a component of vitamin B3 (also known as niacin), by binding to a specific receptor site. Drugs that interfere with this binding should increase sirtuin activity. It is known that resveratrol, found in red wine, can inhibit this interaction and is a putative agent for slowing down the aging process. However, the amount of resveratrol found naturally in red wine is too low to activate sirtuin, so potential therapeutic use would mandate purification and development of a therapeutic agent. Development of new agents that would specifically block the nicotinamide-binding site could provide an avenue to develop newer agents to treat degenerative diseases such as diabetes, atherosclerosis and gout.

Sirtuins types

Sirtuins are classed according to their sequence of amino acids. Prokaryotics are in class U. In yeast (a lower eukaryote), sirtuin was initially found and named sir2. In more complex mammals there are seven known enzymes which act as on cellular regulation as sir2 does in yeast. These genes are designated as belonging to different classes, depending on their amino acid sequence structure.^[6][7]

Sirtuin list based on North/Verdin diagram.^[10]

Companies associated with the sirtuin enzymes

Elixir Pharmaceuticals

Founded by Leonard Guarente of Harvard Medical School, with Cynthia Kenyon of the University of California at San Francisco, with the intentions of treating aging through drugs which affect metabolism.^[11]

Sirtris

Sirtris^[12] was co-founded by David Sinclair^[13] of the Harvard Medical School, and Dr. Christoph Westphal is the CEO. Sirtris is associated with the World Transhumanist Association.^[14]

See also

• Sir2
• Resveratrol
• Biological immortality
• Caloric restriction
• Trichostatin A
• Histone deacetylases or HDACs

References

1. ^ EntrezGene 23410
2. ^ Patient Care, "Do antiaging approaches promote longevity?" By: David A. Sinclair, PhD, Evan W. Kligman, MD.
3. ^ "The quest for a way around aging", Nov. 8 2006, International Herald Tribune. By Nicholas Wade / The New York Times.
4. ^ Massachusetts Institute of Technology, News Office: "MIT researchers uncover new information about anti-aging gene."
5. ^ Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes; http://www.nature.com/nature/journal/v450/n7170/abs/nature06261.html
6. ^ Frye R (2000). "Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins". Biochem Biophys Res Commun 273 (2): 793-8. PMID 10873683.
7. ^ Dryden S, Nahhas F, Nowak J, Goustin A, Tainsky M (2003). "Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle". Mol Cell Biol 23 (9): 3173-85. PMID 12697818.
8. ^ http://focus.hms.harvard.edu/2005/Sep2_2005/research_briefs.shtml
9. ^ Mostoslavsky R et al. (2006). "Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell 124 (2): 315-29. PMID 16439206.
10. ^ North B, Verdin E (2004). "Sirtuins: Sir2-related NAD-dependent protein deacetylases". Genome Biol 5 (5): 224. PMID 15128440.
11. ^ http://www.elixirpharm.com/
12. ^ http://sirtrispharma.com/Home/tabid/3662/Default.aspx
13. ^ Patient Care article by David A. Sinclair, PhD and Evan W. Kligman, MD.
14. ^ http://www.transhumanism.org/index.php/WTA/about