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)
the same article cites Rose on _genetic factors that extend lifespan_ (note: they are not single genes & they were obtained by selecting for old flies to mate) pubmed.ncbi.nlm.nih.gov/28555803/
David cites a paper claiming that fat-specific knockout of the insulin receptor are long lived (ref 27 in David's review). He seems unaware that such mice are not well and are not long lived pubmed.ncbi.nlm.nih.gov/27246738/
When he gets to sirtuins, he fails to mention that sir2 deletion mutants have a longer chronological lifespan
cell.com/fulltext/S0092…
He skips fly & worm sirt1, which have perfectly good mitochondria & then cites 3 papers he says show that SIRT1 stimulates mitochondrial biogenesis but doesn't cite papers that show that sirt1 KO mice respire fine & have a normal lifespan ncbi.nlm.nih.gov/pmc/articles/P…
There's a long paragraph on resveratrol & SRT1720 as pharmacological activators of SIRT1 that was not effectively peer reviewed. Essentially every statement has evidence against it
David makes the _reasonable suggestion_ that mitochondria uncouplers could be used to help burn fuel in overweight conditions but doesn't mention that sirt1 deletion mice overexpress UCP2 ncbi.nlm.nih.gov/pmc/articles/P…
oops, that means that loss of sirt1 would drive uncoupling not activation of SIRT1 would drive uncoupling
I know that everyone is busy but this particular review article is truly plumbing the depths of misinformation

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More from @CharlesMBrenner

Feb 10
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
when you find ppl who claim that their highly specific dietary or health practices are best for you or that by following their practice, they have not only improved their health (entirely possible) but have reversed their age, you've identified a guru & quack
Read 5 tweets
Feb 4
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:
animals have evolved gene sets to pass on their gene sets. life is _amazing_. my life work is understanding metabolism, especially through the lens of 4 NAD coenzymes. our gene sets confer the ability to reproduce multiple times but haven’t been selected for longevity per se.
Read 7 tweets
Feb 3
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
this paper shows that LOSS of SIR2 lives longer pubmed.ncbi.nlm.nih.gov/16286010/ (david doesn’t cite it)
this paper shows that the original claim that fly sirt1 extends lifespan cannot be replicated ncbi.nlm.nih.gov/pmc/articles/P… (david doesn’t cite it)
Read 4 tweets
Feb 1
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
so they keep on repeating the longevity falsehoods even though SIR2 deletion strains live longer in yeast pubmed.ncbi.nlm.nih.gov/16286010/
Read 12 tweets
Dec 31, 2021
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
we eat to live & we live to eat. less processed food is generally better. matching food intake to energy expenditure is really important. becoming ocd about food does not help you live & enjoy your life /3
Read 8 tweets
Dec 15, 2021
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
He showed work from Shin Imai that got him interested in NMN. Said that while others use NR to boost NAD, he uses NMN & that it rejuvenates mice by activating SIRT1. He also referred to lab member(s) working on resveratrol, which he claimed is a SIRT1 activator /3
Read 38 tweets

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