The Rhyothemis princeps Brain Externalization Project

A clinical trial [ Veterans Affairs Topical Tretinoin Chemoprevention Trial (VATTC)] of topical all-trans retinoic acid (tretinoin, Retin-A) had to be halted because the intervention arm experienced higher mortality. The authors indicate that a causal relationship is unlikely, but the finding is a bit troubling nonetheless. The increase in mortality was not attributable to any one specific cause of death. https://jamanetwork.com/journals/jamadermatology/fullarticle/711869 "We considered the possibility that topical tretinoin applied to the face and ears might be a cause of death. One study that was published during our trial involved systemic administration of isotretinoin, a closely related compound. That trial found a significant interaction between the medication and smoking in their effect on mortality, with isotretinoin therapy associated with increased mortality among smokers. 4 Studies involving a less closely related compound, beta carotene, have also suggested an

Glucosamine (credit: AndresJS )   Sometimes I lurk on various life extension message boards and am perplexed that many (most?) people do not list glucosamine in their pro-longevity 'stack' even though its use is associated with reduction in all-cause mortality. Glucosamine is cheap and relatively well-tolerated. While association does not mean causation, the relationship has been found in several large epidemiological studies and holds up when controlling for various demographic factors; similar associations have not been found for other supplements - not even fish oil or vitamin D. There are some plausible mechanisms, which I don't have time to really get into, unfortunately. In brief, glucosamine inhibits glucose metabolism (see Ristow interview linked below) - which could have direct effects and also effects via the gut microbiome, increases hyaluronic acid production, and may have other effects relating to O-GlcNAcylation (that's what I'm most interested i