Obesity drugs have another superpower: taming inflammation

Sounds increasingly like GLP-1 receptor agonists may be longevity drugs:

Evidence suggest that the drugs classified as GLP-1 receptor agonists — a category that includes brand names such as Mounjaro and Wegovy — can reduce inflammation in the liver, kidneys and heart. The drugs even seem to dial down inflammation in the brain, leading scientists to hope that the compounds could be used to treat Parkinson’s and Alzheimer’sdiseases, both of which are characterized by brain inflammation. A recent review1 listed more than 20 clinical trials that are exploring the drugs as therapies for the two conditions.

“The next generation of drugs could be even more targeted to reduce these new inflammation pathways that we’ve identified,” says Daniel Drucker, an endocrinologist at the University of Toronto in Canada who co-authored a study2 investigating how the drugs dampen inflammation that was published last month. “Maybe they would be more effective.”

https://www.nature.com/articles/d41586-024-00118-4

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Very interesting

At this point I’d probably say “health extensions” drugs instead of “longevity drugs” thought

We know they are turning on insuling production 24/7 to higher degreases and not in a natural post randal fashion and that does seem to have risks against longevity

What might be the best if short half life GLP-1 / GIP etc drugs could be developed such that one took them ahead of a meal (kind of like Acarbose, but probably more like 30-60 min before a meal or so, so they have time to trigger less hunger). That way the insulin curve would match when it’s helpful around meals but not re revved up the other 12+ hours when one should be sleeping or otherwise not eating.

Even above might not be good for longevity as even that extra insulin may be too pro growth and damage and not pro hunker down/repair/rejuvenate.

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The impact of neurodegeneration is very different than for longevity though and for higher risk individual one might want to trade neuroprotection for hypothetical longevity impacts.

Here is the underlying main paper:

Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00420-5?

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I hope the exenatide phase 3 trial for PD that ends in a few weeks will succeed… If successful, it would be a massive shock for those who spent years and billions looking at new drugs, whereas the solution has been out there for 20y. A bit like for rapamycin?

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