Valproate is a potentially dangerous drug used for ppl with seizures. Abbott was penalized $1.6 billion for off-label marketing this drug in nursing homes as a sedative /1…
The data in the paper David cites do not show that valproate restores swimming ability of fish--fig. 1D shows that most low dose valproate-treated fish swim WORSE than control. High dose was clearly much worse /2…
The SIRT1 western blots in Fig. 4 are some of the worst I've ever seen published. With respect to swimming, rather than look at dozens of fish as they did in Fig. 1 (already a fishy result), they decided to look at only 3 fish with valproate + EX527 /3…
The paper _does not_ convincingly show that valproate activates SIRT1. However, one has to ask, if you thought that this paper provides evidence that valproate activates SIRT1, knowing as we do that valproate given to ppl without seizures _sedates them_ /4
so that nursing homes can better control them, why would you be trying to develop specific SIRT1 activators to prolong healthy aging? /end

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More from @CharlesMBrenner

29 Aug
Defining age reversal via a score on an aging clock rather than a functional measurement would constitute the single biggest scam in the entire tawdry history of anti-aging scams. let me explain /1
There's a buyer for the promise of anti-aging of course. this person wants to maintain functions for a longer period of time. maybe they run 7 min miles with their grandson, maybe they play competitive chess, maybe they skateboard and need to be able to recover from scrapes /2
Those are functional metrics: running, playing chess, wound repair. in all of animal history, every animal has declined in its motility, mental ability and repair capacity after it reaches some level of maturity. people want to prolong their mastery or better: reverse aging /3
Read 12 tweets
19 Aug
I'll defend model organisms. However, the proposal that something is conserved for longevity needs to be specifically examined. It's time to explain something about yeast that ppl haven't thought about enough and yes, this concerns SIR2 /1
there are two assays one can use to analyze lifespan in yeast. The 1st one is called chronological lifespan. It's simple. Grow a culture of yeast and see how long the cells are viable to form a colony. Chronological lifespan is measured in days or weeks /2
it might surprise you that sir2 DELETION lives longer in this assay. the work was done by Valter Longo and was published in Cell… ... let that result sink in a minute /3
Read 20 tweets
13 Aug
scicomms is very important. if we are making progress on matters related to human health, we should do our best to explain the developments to the general public. however, it must be remembered that the entirety of human history has been marked by false & exploitative claims /1
with respect to longevity. plants & their extracts have always been claimed to have essentially magical properties of age reversal. extraordinary claims require extraordinary proof. journals have repeatedly failed us & have legitimized overblown claims, exciting- /2
sounding mechanisms & nonreproducible results that were heavily biased by models, expectations & the subsequent exploitation of the resulting stories. the longevity field has assuredly been fouled by this stuff. publication & defense of bad science undermines real progress. /3
Read 9 tweets
13 Aug
The Gross Clinic by Thomas Eakins is one of the most important paintings from the 19th century & the history of medicine. It depicts Samuel Gross, teaching surgery to Jefferson Medical College students prior to the use of white coats /1
The black suits were what the students and Gross wore outside on the dirty streets of Philadelphia. Gross gesticulates with a bloody scalpel. The patient’s mother cannot bear to watch /2
This painting was owned by Jefferson and on display in Jefferson Alumni Hall when I was an assistant prof—it was subsequently sold & is on display at the Philadelphia Museum of Art. It is breathtaking.
Read 4 tweets
9 Jul
One of the urban myths of NAD metabolism is the idea that NAD+ is good, while NADH is bad. NAD+:NADH are a redox couple that differ by a hydride group (a proton with 2 electrons) /1
NAD+ picks up the hydride when small molecules are oxidized, forming NADH. NADH donates the electrons to generate ATP and/or heat at the inner mitochondrial membrane. NADH is also the source of electrons in ketone body formation and gluconeogenesis /2
Thus, ketogenesis and gluconeogenesis are run in a reducing environment while fuel oxidation to produce ATP and/or heat requires oxygen as the ultimate electron acceptor to maintain a high NAD+/NADH ratio /3
Read 5 tweets
4 Jul
I'd like to counter some weird obfuscation that appeared today /1
I'm a metabolism scientist @cityofhope. Prior to that I was @uiowa and @dartmouth /2
in 2004, Pawel Bieganowski and I were 1st to describe the NR kinase pathway to NAD+, which--along with 3 related coenzymes--is the central catalyst of metabolism in all forms of life /3
Read 48 tweets

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