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Preprint, not peer-reviewed yet.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?
Lots of things we don't know. Are dogs fed once a day less likely to be obese? More active? Eat different types of diets? Will this replicate in another study population?
What is the metabolic impact of eating once per day in dogs compared to multiple feedings per day? It's my understanding dogs don't go into ketogenesis unless fasted for a couple of days. Other metabolic effects?
This was such a fun way to start diving into the data from the @DogAgingProject Pack. Really enjoyed working with the team on this & especially impressed with the fantastic early-career scientist co-authors @DrEmilyBray @BrianahMccoy and Zihan Zheng

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More from @mkaeberlein

14 Nov
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
The omics data here are compelling that there is a strong rejuvenation effect from parabiosis that persists for some period of time after the treatment ends. The actual impact on lifespan is significant but appears to be much less than 126 ppm rapamycin

/3
Read 11 tweets
18 Oct
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
In fruit flies:

Time restricted feeding (TRF, 12h:12h) did not reproducibly extend lifespan

Intermittent fasting (24h:24-48h) ***shortened lifespan***

A TRF protocol (iTRF, 20h:28h) that induced autophagy at just the right time extended lifespan by ~15%

/3
Read 14 tweets
22 Sep
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
… loss of libido , constipation, diarrhea, nausea, dehydration, irritability, hypoglycemia, halitosis, dysmenorrhea … These are all well-known side effects of fasting. It seems very likely the true AE rate will approach 100% in the CR/IF group /3
Read 6 tweets
19 Sep
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
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
I would suggest that the risk profile for diet interventions is significantly higher than commonly appreciated, including adverse psychological effects. The impact of individual genetic and environmental context is not understood /3
Read 10 tweets
20 Aug
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:

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
The study in question used very young mice that are still growing to test the effects of rapamycin on bone. They found that the mice receiving rapamycin had lower bone density. Importantly, no evidence for lower bone quality or bone frailty, but that was not discussed.

/3
Read 14 tweets
8 Jul
Sort of. For anyone who cares, here is a chronology of the Dawn of Sirtuins, at least as I remember it... /1
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/
They didn't know exactly how it worked but knew it affected distribution of Sir4 from telomeres to the nucleolus and that this mutation delayed degradation of the nucleolus with age
Read 10 tweets

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