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@statto My reading is that these results actually go against mutations being that relevant, given that mice remained healthy (if increasingly less fertile) despite mutational burden.

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@ydeigin If anything, the paper supports your take on aging: after 58 successive cycles scnt, the animals had fertility problems, but were otherwise healthy, *despite* the presence of deletereous mutations. Thus suggesting the later are not the main drivers of aging.

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@davidasinclair @davidasinclair

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@davidasinclair I just wanted to say that, if anything, the paper supports your take on aging: after 58 successive scnt, the animals had fertility problems, but were otherwise healthy, despite the presence of deletereous mutations.

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@jpsenescence Many of these repurposed drugs are quite toxic. Not as bad as old school cytotoxic chemotherapy, but still very prone to cause off-target effects. BCL2 inhibitors are another similar group. Venetoclax has significant toxicities, and navitoclax is WORSE than venetoclax in those.

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@jpsenescence My guess is that it's more related to an off-target effect of dasatinib than to senolysis in general. TKIs have a lot of off-target effects. Neuropathy is reported as frequent in the SPC, and it's reported to cause demyelinating neuropathy on occasion https://t.co/gqMqDLkQaR

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@statto @davidasinclair I think most of the problems are around a poorly drawn X axis and a sort-of-confusing image comment. It kind of feels like they were trying to comment on both graphs at once.

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@mkaeberlein @LongevityDublin Do they even have the capacity to do what they claim to do? It seems to me they're basically claiming to do now what more serious biotechs are developing (except cheaper/earlier) but then become very vague about specifics, EVEN for a low-regulation medical tourism clinic.

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@mkaeberlein @LongevityDublin Honestly, given their "price list" does not even say what each therapy contains (not even in broad terms) I kind of wonder if they are really administering any therapies at all. They don't have any (in-house) publications either.

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@EmanuilDinev @jpsenescence The reported MOAs were different. UBX1325 is reportedly a BCL-xL inhibitor. UBX0101 was a p53/MDM2 interaction inhibitor

https://t.co/eytXYeDSw9

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@EmanuilDinev @jpsenescence Plus: IIRC there was a paper by Kirkland comparing in mice regional vs systemic senolysis. The former was shown to have less of an impact & he theorized that an imporant portion of the benefit was SASP attenuation, rather than ablating the senescent cells themselves.

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@EmanuilDinev @jpsenescence IMO there was bad trial design. It should have been SOC + senolytic vs SOC. Aiming to compete head to head with vegf inhibition in wet AMD (in which VEGF is well established to be a driver) seemed overly optimistic.
The OA drug was a different one & not that active IIRC

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@davidasinclair Also tetraploid complementation (which kind of falls under the umbrella of the above but is OSKM-specific enough to merit a mention)

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@biogerontology @elonmusk If he "went longevity" that'd be a redeeming factor (my opinion of Bezos improved after Altos; likewise with Musk). But it'd be very out of character for him to do it given his record for the last 5 years.

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@biogerontology @elonmusk I know you look up to him, but he just gutted medical research in the US and has been anti-longevity for years. That's leaving aside *all the other stuff* btw.

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@aubreydegrey @iMichaelTen @oregoncitizen_ @sama On the other hand they did plug GPT4b-micro into Retro biosciences not that long ago. I'm optimistic that likewise they will be oriented for longevity here too.

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@jpsenescence One would think the effect on the methylome going beyond the mutation itself is supportive of the disturbances of the former being the driver, not the mutations themselves. Wouldn't this be largely consistent with @davidasinclair 's experiments with ICE mice?

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@antonioregalado @ydeigin @7SecularSermons @OpenAI @RetroBio_ In their website one of their initial programs is to develop autologous rejuvenated HSCs. Better ipsc generating protocols would fit the bill.
They do have a separate partial reprogramming program as well, which will probably get AI support too given the success with ipscs

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@aubreydegrey @biogerontology @HuffPost I think we have made more progress in some of those items than it might seem at first glance. Cell therapy in particular, although tissue engineering is making strides too.
Regulatory processes (specially in the FDA) have improved as well methinks

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@biogerontology It has been slower than expected (going by a regmed paper published 20 years ago) but it hasn't slipped as much as you might think. True, full bioprinted organs arent on clinical trials yet, but bioprinted vessels were fda approved on dec 24. And then there's the xenotx trials.