NAD metabolism / quantitative mass spec /
Fatty liver, diabesity & cancer /
Dept Chair @CityofHope /
Truth in science /
Tweets are mine alone
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Jul 12, 2023 • 10 tweets • 2 min read
today @davidasinclair is telling the world that he has achieved age reversal with chemical cocktails
he submitted the paper on June 30 & it was accepted on July 4 by a journal of which he is coeditor-in-chief
paper was sent to me 3 days ago by a reporter for comment
reporter was told it is a "groundbreaking study" & "the first chemical approach to reprogram cells to a younger state"
May 11, 2023 • 10 tweets • 3 min read
a lesson about selected traits & how to tell if someone is BSing about aging
look in the animal word, especially wild animals:
animals are clever, terrific at finding food, protecting themselves & their babies
they use strength, appearance & guile to mate
1000s of genes
are required for these abilities & they are selected:
animals w good brains & musculature have babies w good brains & musculature
animals that can't see or smell predators don't survive & therefore contribute little to the gene pool
that's how selection works
dobzhansky said
Jan 12, 2023 • 4 tweets • 2 min read
there's a peer review failure today doi.org/10.1016/j.cell… in which an individual with 59 collaborators claims to have tested the information theory of aging
he did not test the information theory of aging
the claim is that he induced dsDNA breaks that are easily repaired, don't cause a DNA damage response or mutagenesis or cell death--only an epigenetic change
he knows this is not true because his co-first author & he published this paper in dec '21
there are a few issues being addressed here. let’s start w safety
human placebo controlled trials have never shown adverse events attributable to Niagen. note that LDL-C is raised in humans w Basis & pterostilbene alone
the class of compounds to which NR belongs is vitamin B3
there are decades of human data on these molecules showing human safety. niacin is unique in causing flushing but nicotinamide was tested in large Australian skin cancer and was shown to be cancer-preventative in ppl
Nov 17, 2022 • 8 tweets • 2 min read
with ppl's heightened awareness of NAD, it's important to reset expectations on aging and what the use cases are for compounds like NR
aging is not optional
if you are reading this, you are aging
you can age poorly or you can age better but you are going to age
human aging is remarkably different from yeast, worm, fly & mouse aging
it is not true that dominant longevity genes found in yeast promote longevity in ppl
while it is true that there are worm & mouse mutants that are extremely long lived, they are sterile dwarves
Sep 19, 2022 • 16 tweets • 2 min read
🧵
the ancient writer Herodotus is considered the father of history
in his writings are legendary waters that allow its inhabitants to stay forever young
the story was bullshit of course
explorers used such stories to go on adventures and conquests
around 120 yrs ago, Diamond Lil MacConnell created a Florida theme park out of a well on her property but the waters have no magical property
faculty & trainees are consistently astonished by the house of cards built by influencers
so many ppl have been drawn into this by stories, model bias, confirmation bias & obfuscation
i will release a 1 hr version of the lecture
it's updated wrt monogenic longevity genes. while sirtuins are clearly not monogenic longevity genes even in yeast,
daf-2 & other genes in GH signaling for sure confer long-lived phenotypes w loss of function
Apr 23, 2022 • 6 tweets • 2 min read
super weird study. they measured NAD in serum using a cycling assay. you do not get quantitative data from a cycling assay. worse, NAD is not in serum. everyone knows NAD is in the cellular fraction of blood. so the NAD measurements are GIGO
2nd, they did a 6 min walk test for all the groups. their placebo group walked slower at 30 days. they decided to compare the improvement in walk speed on NMN to the spurious placebo data at 30 days. note that the data are just noisy and at 60 days the placebo had no effect. GIGO
Apr 13, 2022 • 6 tweets • 2 min read
disagree
are sirt genes conserved as longevity genes? definitely not. the mother cell helped by SIR2 is 1 of 2 million. the whole culture of yeast lives longer if you delete SIR2. you cannot say that organisms have sirt genes to live longer if they live longer without this gene
when a premise is nullified, we need to change our thinking
we can’t keep stating we want to activate sirt genes bc they are conserved longevity genes once we found out that they aren’t longevity genes
Apr 12, 2022 • 4 tweets • 1 min read
Adam is my friend but I disagree. Public health measures are known extenders of healthspan and lifespan. Ppl are also still arguing about diet & biomarkers (eg LDL-C) wrt to health & mortality. Research & education are clearly necessary to lower incidence of diabetes, cancer,
heart disease, neurodegeneration dz, all of which have lifestyle components.
longevity is not a branch of biology or medicine. it is an emergent property of wellness. ppl who say that ppl need to specifically work on aging always gravitate to the 1 thing they work on claiming it
Mar 27, 2022 • 7 tweets • 3 min read
DS wrote his book during '16-'18, describing the OSK experiment & claiming reversal of aging with no teratomas or cancer. @nature published the result end of '20 w the statement "the investigators were blinded to animal allocation but not cell cultures or outcome assessment"
since the book release in '19 & potentially earlier, his lab has been under pressure to produce this result. he claimed rejuvenation wo teratomas in the book
there are always sick mice in the vivarium. staff are required to sacrifice mice w weird growths & that are suffering
Mar 18, 2022 • 5 tweets • 1 min read
much of the current thinking on lifespan is mispremised based on someone telling us we don’t have to age
we do age & humans have an apparent max age ~120
supercentenarians have great genes & did a lot of things right
calorie restriction is the norm in animal evolution. animals generally wake up & expend their day acquiring the fuel they need. animals didn’t evolve w a garage or a fridge full of provisions
Feb 27, 2022 • 12 tweets • 3 min read
cannot speak for all but will summarize my assessment of the totality of @davidasinclair scicomms about aging:
1-he figured out how SIR2 extends lifespan in old yeast mother cells. TOTALLY ACCEPTED. realize that this is a mechanism confined to yeast & not genetically selected for aging--note that loss of SIR2 extends yeast chronological lifespan in yeast cell.com/fulltext/S0092…
Feb 13, 2022 • 24 tweets • 7 min read
in 1997 David was a postdoc with Lenny Guarente & published a very nice paper showing that SIR2 extends the number of times a yeast mother cell can produce daughter cells by controlling formation of ribosomal DNA circles doi.org/10.1016/S0092-…
David knew then that rDNA circles don't exist in other organisms & he knew that there are extremely few old mothers in a culture. Here's a quote from the paper "50% have no bud scars, 25% have 1, 12.5% have 2, etc. Among 100 cells counted, no cells had greater than 6 bud scars."
Feb 11, 2022 • 10 tweets • 3 min read
this is a massive peer review failure that allowed David to say things completely unsupported by evidence. some lowlights:
in the 2nd paragraph, he claims that the possibility that ageing is simply caused by genetic factors can be ruled out, citing ncbi.nlm.nih.gov/pmc/articles/P… the article shows that human lifespan was extended in the 20th century by public health measures (we all know this)
Feb 10, 2022 • 5 tweets • 1 min read
orthorexia nervosa is a disorder of the worried well. such ppl are trying to eat clean or eat healthy bc of something they read on the internet
they may have been told that they need to do intermittent fasting, keto, all plants, no plants, etc etc in order to be healthy
most of these practices are not sustainable for most ppl
developing an obsessive relationship with food is not healthy
coming to believe that a health influencer has discovered a protocol to reverse their age is not healthy
Feb 4, 2022 • 7 tweets • 2 min read
i learned today that quite a few ppl think that new research has _solved aging_. they don’t think the comparisons to old fountain-of-youth claims are fair. i could be wrong but i don’t think most of the believers know as much as i do
about model bias, confirmation bias, replicability, what single genes can & cannot do, & how hard it is to put the genie back in the bottle when great stories are told. some think i’m a downer but i’m telling you what biologists have understood for decades:
Feb 3, 2022 • 4 tweets • 1 min read
we’ve entered the 3rd decade of the sirt saga. these data show longer mean lifespan of flies w more sirt6 but note that yeast w sir2 deletion have a longer chronological lifespan & that the fly sirt1 lifespan result doesn’t replicate. but david will never stop selling this story
the SIRTs as longevity genes in animals story was debunked 10 yrs ago by researchers from 9 institutions ncbi.nlm.nih.gov/pmc/articles/P…
guarente & sinclair had already told us that sirt1 is the human longevity gene but they pivoted & started nominating other sirt genes. there was also a ton of $, effort & careers tied to this dominant longevity gene hypothesis
Dec 31, 2021 • 8 tweets • 2 min read
a 🧵 for folks who want to learn more about nutrition & metabolism in 2022 /1
there will be lots of ppl telling you what you can & what you cannot eat. none of the extreme diets (eg all meat or all-cleanse) make sense. intermittent fasting doesn’t agree with most ppl & has not been shown to promote wt loss in ppl /2
Dec 15, 2021 • 38 tweets • 9 min read
lots of ppl have requested a summary of the 1st hr of nia.nih.gov/news/virtual-w… in which @davidasinclair & I spoke back to back. ~200 ppl attended. it was recorded by @nih for their benefit & many of us took notes /1
David began by claiming that he & others have discovered 7 genes called sirtuins that are longevity genes & that are primary mediators of the effects of boosting NAD. He showed a diagram of a man's body in which SIRTs were shown in essentially every tissue as key NAD mediators /2
