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Charles Brenner, PhD Profile picture
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Feb 3 • 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
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)
the magazine articles will come out: could sirt6 be the fountain of youth?

narrator: no 🔚

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Charles Brenner, PhD Profile picture
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
Charles Brenner, PhD Profile picture
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
Charles Brenner, PhD Profile picture
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
Charles Brenner, PhD Profile picture
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
Charles Brenner, PhD Profile picture
Oct 11, 2021
organisms’ lifespans are determined by their genes & environment. we can modify our environment (diet, exercise, sleep, etc). we can modify gene activities w drugs/vitamins or possibly w CRISPR but we 1st have to understand the process of aging itself to know what to target. /1
the gene set any organism has was selected for in evolution. parents who produce lots of reproductively successful offspring pass on their genes. the selections for these genes took place over evolutionary time in conditions that were different from current conditions. /2
most animals achieve reproductive capability early & don’t live much longer than they can reproduce. why? bc the brain, liver, musculature, etc are there to present males to females & help us care for young til they are reproductively capable.

this is the way biology works. /3
Read 13 tweets
Charles Brenner, PhD Profile picture
Oct 4, 2021
Living things maintain their order by taking in fuel to run chemical reactions. the fuels are protein, fat & carbohydrate. in common parlance, we burn these fuels to generate ATP that runs chemical reactions, to make everything in our bodies, repair everything, move & think. /1
Fully oxidized, the carbon in the fuels is exhaled as CO2. /2

The energy in the fuels consists of high energy electrons, whose energy is derived from the sun (that lesson for another day). /3
The difference between living things & locomotive machines that imparts the ability to build ourselves is that we have NAD coenzymes that capture the energy associated with fuel oxidation in a nearly lossless manner. /4
Read 8 tweets

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