November 28, 2002
Clue For Life Extension By Calorie Restriction
In a large number of species it has been found that a calorie restriction (CR) diet increases lifespan. Scientists have been looking for a clue as to what molecular mechanisms are at work in CR that cause a slowing in the rate of aging. A possible clue has been found in experiments on fruit flies:
In a report in Friday's edition of the journal Science, researchers said studies with fruit flies, which have many genes similar to mammals, showed that an enzyme called Rpd3 histone deacetylase likely is a key to longevity.
"If you decrease the level of enzyme without eating less, you still get life span extension," said Stewart Frankel, a Yale research scientist and the study's senior author.
This result needs to be repeated in a warm blooded mammalian species. Another avenue of investigation would be to try to find pharmacological agents that will block the activity of Rpd3 histone deacetylase in mammals.
A currently available drug called phenylbutyrate (trade name triButyrate www.tributyrate.com) used to treat urea cycle disorders has been shown in a study by Kang (http://seroudelab.biology.queensu.ca/pdf/kang.pdf) to affect Rpd3 and "significantly increase lifespan, without diminution of locomotor vigor, resistance to stress, or reproductive ability" in the Drosophila fly. Since it is legal to use for other disorders, doctors have the discretion to prescribe it for off-label uses. Anybody tried this?
It looks like phenylbutyrate goes under the trade name buphenyl in the U.S. Dosage for treatment of urea cycle disorders appears to be up to 40 tablets a day. You can get 300 tablets from drugstore.com (with a prescription of course) for $1,337.68, so that is a little over $1000 a week. I guess you'd have to be pretty damn wealthy to explore this option, if dosage as an anti-aging therapy is similar.
My company supplies Sodium Phenylbtyrate (powder) and SPB11 (Tablets) in the USA for clinical trials -- various divisions of NIH including National Institute on Ageing. You should visit and revist their website for updates.