I would encourage folks working at the interface of nutrition and longevity to start taking a more rigorous and critical approach toward their specialty. The ongoing lack of quality review here contributes to a reputation problem among the broader scientific community

1/17

https://twitter.com/LammingLab/status/1674792116470575113

First, I want to be clear I believe in the importance of this area of research @NIH @NIHaging. It sounds like many good insights came from this event. Congratulations on a successful meeting

2/17

This looks ok at first glance. Not as good as rapamycin (had to say it), but decent absolute and relative effects, at least in females. Here’s my method for quickly assessing claims of lifespan extension in mice in under 60 seconds /1

https://twitter.com/agingdoc1/status/1618320431592919040

Check the absolute control and median lifespans. To do this simply start at 50% (or 0.5 depending on units) on the y-axis, look straight across to the survival curve, then look straight down when you hit the line. Where your eyes hit the x-axis will be approximately median /2

This study published in @GeroScienceAGE has some significant limitations that IMHO preclude any interpretation at all. It is being misrepresented in ways that are potentially damaging to the field. I will attempt to explain why /1

https://twitter.com/LongevityGL/status/1617547015449382914

The study attempts to ask whether drugs that extend lifespan in worms and flies are predictive for lifespan extension in mice above random. An important question, but one that is not possible to answer given the data currently available /2

Ok folks, pay attention. Percent lifespan extension means nothing when the controls are short-lived. The next time someone Tweets about how “X increases lifespan in mice by Y percent!!!”, first thing you should do is look at the absolute lifespan of the controls /1 Short-lived controls are a major source of false-positive results in mouse lifespan studies. Metformin, nicotinamide riboside, intermittent fasting all suffer from this flaw. This graphic illustrates the problem /2

I’m pleased to announce the official launch of the UW Rapamycin Study funded by the Impetus Grants program. Website is live and the we are actively recruiting participants:

rapamycinstudy.org

Please RT! @Blagosklonny @MartinBJensen @RapaNews

/1 We are seeking people who have previously taken rapamycin (sirolimus) to tell us about their experiences. After completing informed consent, participants receive a unique ID and complete a series of short survey modules

/2

Here’s a detailed explanation with sources for my graphic illustrating potential effects of targeting aging with rapamycin in humans. This is based on a *speculative* extrapolation from mice to humans /1 The graphic represents impact on life expectancy for a typical 50 year old woman from curing cancer or heart disease and comparing it to potential impact from an intervention like rapamycin that targets biological aging. Green = healthy years, red represents unhealthy years /2

The best opportunity to end cancer as we know it is through targeting the biology of aging, something that is feasible today. It's time to leave behind the one-disease-at-a-time approach and embrace 21st Century Medicine #geroscience @EricLander46 @POTUS

https://twitter.com/EricLander46/status/1463195009004486661

@EricLander46 @POTUS Cancer was the second leading cause of death behind heart disease in the US in 1971 when the War on Cancer was declared. Cancer is still the second leading cause of death behind heart disease in 2021

jamanetwork.com/journals/jama/…

Really interesting pre-print on effects of middle-age parabiosis in mice. Definitely worth a read.

biorxiv.org/content/10.110…

I like the design here, as it parallels what we did with rapamycin in 2016. Treat from 20-23 months of age and see what happens

/1 I recommend everyone directly compare the two studies

elifesciences.org/articles/16351

We didn’t do multi-omics in our 2016 rapamycin study, but we did do some function measures and disease pathology not included here. Both studies reported lifespan extension

/2

Once-daily feeding is associated with better cognitive function and health in companion dogs @DogAgingProject biorxiv.org/content/10.110…

Preprint, not peer-reviewed yet. Correlation does not equal causation. Still, really interesting I think! @DrEmilyBray @BrianahMccoy For those who know me, you're aware I'm not a big believer in time restricted feeding (I like to eat). And this study absolutely doesn't prove TRF is causal for the observed association with reduced disease risk in dogs. But it's intriguing, isn't it?

For those who want to get beyond the pop-sci diet guru analysis, here’s a little deeper dive on this recent time restricted feeding paper in @nature

nature.com/articles/s4158…

/1 Strongly encourage you to *read the paper* and reach your own conclusions. As always, I welcome feedback if you think I got something wrong, but here’s what I took away:

/2

Drugs versus diets: Here’s some data to support my assertion that rapamycin as a pharmacological intervention for healthy aging is likely to have a better side effect profile than dietary interventions /1 Consider a hypothetical clinical trial of caloric restriction or intermittent fasting. Nearly every participant will experience multiple of the following adverse events: dyspepsia (hunger), headache, dizziness, fatigue, insomnia, poor thermoregulation, … /2

Genuinely surprised at the response this Tweet is getting and how many folks were unaware of the data showing caloric restriction is not universally beneficial. Many people assume these diet interventions have no risk, which is obviously false /1

https://twitter.com/mkaeberlein/status/1438965248204042243

I’m not trying to bash caloric restriction/intermittent fasting/time restricted feeding. The science is important, and I think many people obtain health benefits. Although those who would probably benefit most are least likely to actually practice them IMO /2

Recent discussion between @Blagosklonny and @LammingLab brings up a couple of ideas worth expanding on because they are often misunderstood. Both make important points /1

https://twitter.com/LammingLab/status/1429966242841079810

None of the newer mTOR inhibitors have been yet shown to work as well as rapamycin for aging or to have convincingly reduced side effects. Testing these molecules is important, because there is some reason to believe they might /2

A few days ago I chose to call out a misleading Tweet by my friend and colleague @lamminglab that appears to endorse a flawed interpretation of a new study testing the effects of rapamycin on bone in young mice:

https://twitter.com/LammingLab/status/1426905471638724615

You may wonder, what’s the point?

1/ IMO, one reason for being on Twitter as an expert in #geroscience is to try to prevent misconceptions and misinterpretations that have the potential to damage the field. This appears to me as a classic example of how misinterpretation can potentially do great harm

/2

Sort of. For anyone who cares, here is a chronology of the Dawn of Sirtuins, at least as I remember it... /1

https://twitter.com/CharlesMBrenner/status/1412502316414996480

Nic Austriaco and @BKennedy_aging were studying aging in yeast and identified a lifespan extending mutation in a protein called Sir4 (not a sirtuin) that physically interacts with Sir2 at telomeres. /2

pubmed.ncbi.nlm.nih.gov/7859289/