Matt Kaeberlein

Debate on Montana's Right-to-Try is a good thing. We need to confront why Montana and other reform efforts emerged. The existing FDA regulatory system has become prohibitively slow and expensive, increasingly favoring large pharmaceutical companies while leaving patients and smaller innovators with limited options. Meanwhile, inadequate enforcement of existing regulations has allowed an enormous black market for unapproved peptides and other experimental products to flourish.

The status quo is not a defensible alternative simply because proposed reforms carry risks of their own.

Patients deserve better than what the FDA is currently delivering.

linkedin.com/posts/mkaeberl…

Another example of "science by press release", which isn't really science at all.

A publicly traded company puts out a press release announcing amazing results for their gene therapy *before* even presenting it at a conference let alone publishing in peer-reviewed literature, and @LongevityTech writes a glowing article claiming in the headline that the therapy "turns back aging in dogs".
longevity.technology/news/genflows-…

I get that Longevity Technology is a trade journal, but this is pure hype without even a shred of journalistic effort put into skeptically evaluating the claims.

To be clear, I know nothing about whether this therapy actually works or not, and that's the point. As far as I can tell, there is no preprint and no data available anywhere to evaluate the claims. In the long run, this will either hold up or it won't. I hope it does. But the trend of "publishing" results through press release is not healthy for science or for longevity.

I was pleased to contribute to a new @NatGeo article from Hannah Singleton out today exploring one of the more interesting questions in longevity science: Could GLP-1 drugs actually slow aging?

It’s a thoughtful look at both the excitement around GLP-1s and the important uncertainties that remain. My view is that there is compelling evidence that GLP-1s can improve multiple aspects of health in humans. Beyond weight loss and glucose control, there are signals for cardiovascular, kidney, inflammatory, and perhaps neurological benefits. That makes me optimistic about the use of GLP-1 agonists in proactive healthspan medicine, potentially at doses and quite different from those currently used to treat obesity.

But, do they slow aging? And if so, are they anything more than a pharmaceutical way to induce caloric restriction?

The recent @Nature paper showing that semaglutide extends lifespan and improves multiple age-related phenotypes in mice is interesting. As I’ve commented publicly, however, the lifespan experiment did not include a calorie-restricted control matched for the reduced food intake caused by semaglutide. Weindruch and Walford showed in 1982 (DOI: 10.1126/science.7063854) that mid-life initiation of moderate caloric restriction increases lifespan in mice by almost exactly the same amount, in the same mouse strain background, as semaglutide in the current study.

So, we still don’t know whether semaglutide is doing something fundamentally different from, or additive to, eating fewer calories.

Regardless of the answer, I think these are extremely promising drugs when used carefully, in the context of high-quality nutrition and regular exercise, expecially resistance training to maintain muscle.

In fact, GLP-1s could ultimately prove extremely valuable for extending healthspan, even if they don’t slow biological aging at all. Preventing or delaying several major causes of morbidity could have enormous value independent of whether we ultimately classify these drugs as true gerotherapeutics.

For me, the most interesting next step is figuring out whether there are doses and protocols where the healthspan benefits substantially outweigh the risks, particularly in otherwise healthy middle-aged and older adults. That’s a question we can answer, and I'm optimistic the answer will be "yes".

nationalgeographic.com/health/article…

And because I can't help myself, here is the data from the recent semaglutide @Nature paper plotted on the same graph as the Weindruch-Walford caloric restriction experiment from 40 years ago.

Interesting question: Would semaglutide + 30% CR approach the effect seen here?

That would be nice. Or people could just learn the simple 900-day rule. If the controls approach 900 days and you see lifespan extension on top of that, it's probably a real effect. If your "long-lived" mice don't live at least 900 days, don't get too excited. There's a decent chance it won't be reproducible.

@Aging_Scientist actually performed and published a nice analysis showing this works pretty well, and it takes only seconds to implement: pubmed.ncbi.nlm.nih.gov/39332712/