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Charles Brenner, PhD Profile picture
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13 Aug, 4 tweets, 1 min read
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.
Eakins depicted himself behind Gross’s right shoulder!

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More from @CharlesMBrenner

Charles Brenner, PhD Profile picture
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
Charles Brenner, PhD Profile picture
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
Charles Brenner, PhD Profile picture
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
Charles Brenner, PhD Profile picture
27 Sep 20
our lab's foundational discovery is that the 4 NAD coenzymes, Crown Jewels of metabolism, are not locked in a vault inside a castle & patrolled by guards. instead, they are exposed to the elements of metabolic stress. many conditions of metabolic stress disturb NAD systems. /1
alcohol, overnutrition, deafening sound, DNA damage, ROS, heart failure, neurodegeneration, inflammation & infection ALL disturb NAD systems in one or more tissues. aging reportedly disturbs NAD, though the evidence is weaker than in all other conditions. /2
when NAD comes under attack, repair processes are compromised, ATP generation is impaired & anabolic processes are disturbed. attributing all of NAD metabolism to SIRTs is just dumb & should have been checked by good reviewers >10,000 publications ago. /3
Read 8 tweets
Charles Brenner, PhD Profile picture
29 Jul 20
NAADP is one of the most peculiar & powerful NAD metabolites: a calcium mobilizing 2nd messenger that is important for cell migration in response to IL8. For yrs, it was known to be produced by CD38 but how? We now know dx.doi.org/10.1096/fj.202…
It had been proposed that CD38 reacts on the outside of cells with nicotinic acid (NA) & NADP in an exchange reaction that would form the NAADP plus NAM but there are problems with this idea
1st, there isn't sufficient NA to do this rx. 2nd, forming NAADP outside of cells doesn't solve the problem of calcium mobilization from acidic intracellular stores. 3rd, there has to be a specific signal to form NAADP. NAADP is too powerful to be made willy nilly
Read 10 tweets
Charles Brenner, PhD Profile picture
25 May 20
every week, i get an email from a desperate parent whose kid has a potentially incurable cancer, asking if they should take #NR, often in a cocktail with resveratrol & other stuff /1
experiences like these make me shudder at the 💩 being peddled in the name of "anti-aging." no phd scientist should tell any such parent that their kid's rare malignancy is curable with their favorite elixir /2
i remind ppl that NR is active in many rodent models of human diseases & conditions of metabolic stress in which the NAD system is under attack (heart failure, fatty liver, neurodegeneration, central brain injury, etc) /3
Read 10 tweets

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