Lamming Lab

I’m excited to share new work out of the lab at @NYULangone led by @kenjifujihara! We took a first principles approach to evaluating #ferroptosis induction for cancer therapy via targeting the SLC7A11-glutathione-GPX4 axis. biorxiv.org/content/10.648…

@TaoofWill1 @davidasinclair @grok No protein powder was used here - diets built up from individual amino acids so the role of each individual amino acid can be studied

@davidasinclair @LammingLab Is this another study where 95% of the protein powder used was plant based? @grok This grouping of proteins under one umbrella term really needs to stop.

Why protein powders & shakes could be accelerating brain aging Great work @LammingLab🐁

@exfatloss @OminousRhombus Meanwhile most other literature calls a “low protein diet” even for clinical trials something like 13% protein. So twice as much as PR. I have to imagine back in prehistory people were closer to the RDA or at least balancing extra protein intake with a lot more exercise

@exfatloss @OminousRhombus It’s an interesting question, because our protein restricted diets (for mice and for the ~three published short human clinical trials) is around 7%, yet the humans in these trials are still getting the RDA for protein.

Isoleucine restriction makes lady mice immortal🤯

@agingroy @ColumbiaOBGYN @NatureAging I haven’t been able to find published results from VIBRANT II and as far as I know the initial phase only tested safety. If results have actually returned please post a link here!

Ovaries age 2.5x faster than any other organ. For decades, nobody studied why. A weekly rapamycin pill just changed that. @ColumbiaOBGYN's VIBRANT trial: egg loss dropped 70%, from ~50 to ~15 per month (n=50). VIBRANT II expanding to 1,000 women. Why it works: a @NatureAging atlas mapped 3,455 aging genes in human ovaries and found mTOR hyperactivity as the dominant ovary-specific aging pathway. Rapamycin inhibits mTOR. The biology lined up. Why everyone should care: -> Women live ~5 years longer but spend 25% more of their lives in poor health. -> The 290 genetic loci controlling menopause timing sit in DNA repair pathways that govern aging itself (Ruth et al., @Nature 2021). -> Early menopause predicts accelerated biological aging. -> Menopause timing isn't just a fertility marker. It's a longevity biomarker. In November, the FDA reversed two decades of hormone therapy warnings. The science caught up. We excluded women from aging studies until 2016. The fastest-aging organ in the human body was in women the entire time.

Men lose nearly a year of life to a molecule that's supposed to boost their brains. Tyrosine, a dopamine precursor taken by millions as a cognitive supplement. @uk_biobank Mendelian randomization (MR), n=272,475: it causally shortens male lifespan by 0.91 years (p=0.01) No significant effect in women. Men naturally carry higher circulating tyrosine than women. The authors suggest this single amino acid difference may partly explain the male-female lifespan gap. Nuance: MR captures lifelong endogenous exposure, not supplement effects. But the finding held across multiple MR methods and every sensitivity test. If you're supplementing tyrosine daily, this paper deserves your attention.

@JohnGolf_CA @exfatloss In general for protein restriction metabolic difference in sex response seems to be mediated by ovarian hormones making female mice less sensitive but a lot unknown.

@LammingLab @exfatloss Immortal is a stretch, but that IleR survival bump is striking. What's behind the sex difference in longevity response?

@exfatloss We previously showed protein restriction also prevents or delays AD pathology in a mouse model of AD. Here, we point to BCAAs being the mediators of this effect. But there is also human data associating BCAAs with AD. Of course we need to eat a certain amount of protein to live!

So you're saying Protein causes Alzheimer's

@naasking @davidasinclair Thinking of writing a paper or blog post entitled “it’s mice and their response to protein and amino acids mirrors that of humans”. Not true for a lot of other things but for protein there are so far few differences!

@davidasinclair @LammingLab It's mice though.

@dooonoten No argument there! We have found resistance exercise training protects mice from some negative metabolic effects of high protein. On the other hand is everyone buying protein water by the pallet at Costco and protein foam shots at Starbucks exercising enough to get that effect?

@LammingLab Humans who supplement with protein/BCAA tend to do so in the context of a sports/training regimen. In other words, you need to add physical activity (often intense, resistance and cardio) into the mix.

Please enjoy the latest publication from our lab "Restriction of Individual Branched-Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice"

@davidasinclair Thanks!

@JohnGolf_CA Agreed - isoleucine restriction is the GOAT of the BCAAs for healthy aging, and conversely more isoleucine seems to be quite problematic in many contexts.

@LammingLab Love this granular approach! The divergence between IleR and LeuR survival curves shows how blunt blanket BCAA restriction is. Ile might be the metabolic rogue here. Great work 👏

With help from @AttieLab's lab a data visualization and analysis tool - we hope to make this tool more broadly available soon: connect.doit.wisc.edu/dlamming_BCAA_…

This work was made possible with the support of many collaborators in and outside the lab, including @garacreen Luigi Puglielli @WiscoSurgMetab @AttieLab and @CholsoonJ!

Glad we were able to help this podcast happen!

Had a fantastic metabolism and aging retreat yesterday with the @JudithSimcox and @WiscoSurgMetab labs!