My Authors
Read all threads
Why do I point out that the foundational SIR2 and sirtuin data are deeply flawed? Because more than a decade of papers on yeast, flies & worms shaped expectations of what sirtuins would do in vertebrates (extend lifespan) /1
It is true that sirtuins use NAD+ to modify protein function by removing acyl groups from protein lysines. It is not true that they are essential for the longevity benefit of calorie restriction. It is not true that they are the primary mediators of NAD /2
It is distinctly wrong that they are critical regulators of DNA repair. It is not true that they are essential for mitochondrial biogenesis or mitochondrial function. All of these ideas were suggested, however, by papers in model organisms that turn out to be wrong /3
The early studies created model bias: that SIR2-related genes could best be explained as longevity regulators. And confirmation bias: that these genes would have positive roles in longevity /4
Thus, when ppl looked at sirtuins in flies, worms & mice, they tended to look for longevity advantages & were able to publish papers that showed these positive results. Now we know that many of the foundational papers are not reproducible, were overhyped & are simply wrong. /5
In actual fact, SIR2-related genes don't do the same things in different tissues. We've known for almost 20 years that SIR2 mutants live longer (not shorter) in 1 of the 2 yeast assays for lifespan (chronological lifespan as opposed to replicative lifespan) /6
Rather than look at the data dispassionately, SIR2 proponents told you that sirtuins were conserved as longevity genes. They could have just as easily told you that sirtuins were conserved as antilongevity genes based on yeast but they didn't & they never will /7
Instead, they claim that sirtuins are the 7 most important longevity genes in people (they aren't), that sirtuins mediate the key effects of NAD (no reason to expect they do), & they make up fanciful stories about resveratrol activating SIRT1 (it doesn't) /8
The functions of NAD+, NADH, NADP+ & NADPH are mediated by scores of enzymes that are essential for energy generation & conversion of everything we eat into everything we are & do /9
Though they have been appealing to editors, models that invoke magical sirtuin functions stand on weak premises & are not evidence-based. Time to learn metabolism & especially conditions that disturb the NAD system & realize that SIRT-centric models are the sign of a cult /end
Missing some Tweet in this thread? You can try to force a refresh.

Enjoying this thread?

Keep Current with Charles Brenner, PhD

Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

Twitter may remove this content at anytime, convert it as a PDF, save and print for later use!

Try unrolling a thread yourself!

how to unroll video

1) Follow Thread Reader App on Twitter so you can easily mention us!

2) Go to a Twitter thread (series of Tweets by the same owner) and mention us with a keyword "unroll" @threadreaderapp unroll

You can practice here first or read more on our help page!

Follow Us on Twitter!

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just three indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3.00/month or $30.00/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!