Generative protein design is transforming macromolecular drugs, but de novo designed therapeutics could still be hindered by immunogenicity in the clinics. Excited to introduce MESSI, a discrete diffusion model for generative protein deimmunization.

Guys we need to get serious here: The new paper barely nudges our priors on GLP-1 for longevity. I'm spending every waking moment pushing for progress on longevity, but what's going to get us there is scaling up truth-seeking, not giving in to slopulism. Publishing this in Nature is IMO a failure of human taste and judgement. First, the sema mice don't really live longer than healthy controls in other studies (see pic). If you stop there, this should be seen as 'nice someone did this, now do it more carefully'. This may be robust life extension it may not. Second, we already know reduced food intake extends mouse lifespan. Why is there are whole figure comparing CR and sema effects, but no lifespan for matched food-intake? Because it should turn paper into 'sema reduces mouse food intake' If you want to keep going, why females only? Blah blah male aggression, that doesn't stop various ITP interventions from working in males. Or is it that constant injections shorten lifespan, possibly via ulcerative dermatitis which is more common in females? No non-injected control group, can 't say. Fig 3 "GLP-1 ... alleviates the hallmarks of ageing and mimics the calorie restriction response" yes reducing food intake is similar to reducing food intake. Fig 4 "modulates the genetic regulators of ageing" -> Show a bunch target genes many of which have been tested and don't nudge lifespan. I'm glad someone did this study, I'm not saying it's not a contribution or should be retracted, but the reason this is in a tier 1 journal is because it'll get attention (boosted by hypefluencers). Apparently some journals are just giving up; I understand that the multi-year assault on truth-seeking is really hard, it's hard to imagine journals not getting replaced by AI if they lean into slopulism.

This is a slide from Terence Tao's 'Math 2.0' public lecture yesterday evening at Caltech. I am highly confident that, if the cure actually worked, almost any Stage 4 cancer patient would tell you that human comprehension of its mechanism is completely irrelevant to them.

1/3 At the 7th TimePie Longevity Forum, Kejun Albert Ying, PhD, a postdoctoral fellow at Stanford University, discussed “AI for Aging: Toward the world model for human health.” His premise: health is multimodal and continuously changes across the life course. #TimePie