Bicep
#11
Thanks, I wondered about this. I take it and got a bunch of it cheap from India and am using it up even though it seems like it does nothing at all. Maybe the stats say nothing happened, but it looks to me like it hurt them a little until the last few.
1 Like
jjrap1
#12
@Josh: I think I donated sometime in October.
@Bicep: Yeah, doesn’t look particularly optimistic for C. elegans, but what does that say for humans??
3 Likes
According to Dr. Kaeberlein, the thought process is that if it’s good for C. Elegans, it may be good for humans. However if it is bad for C. Elegans it’s most definitely bad for humans.
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adssx
#14
That’s why it would be amazing if they could at least release the results of compounds that failed. (while keeping private the IP on successful interventions.)
I’ve also just emailed them about adding semaglutide, selegiline and sotagliflozin to the list. Are there other interesting agents not listed?
7 Likes
I have had conversations with them about citrate, but they seemed to get overcomplicated about it wanting to source it from a pharma type source rather than either from me or off Ebay.
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adssx
#16
In terms of lipid-lowering treatments, which one could be interesting to test? Fenofibric acid? Rosuvastatin? Ezetimibe? (Gemfibrozil already mentioned here).
3 Likes
AnUser
#17
Lipid lowering treatments longevity/healthspan effect is pretty much mediated on its effect on ASCVD so I don’t think we should expect any interesting result.
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adssx
#18
I agree, but who knows? Some drugs also act on unexpected pathways…
Also, I just found this: Ezetimibe increases resistance to oxidative stress and extends lifespan mimicking dietary restriction in Caenorhabditis elegans
It’s not a great journal, but is it worth replicating?
4 Likes
adssx
#19
Actually, ezetimibe might have some potential among men, even though CIs include the null, but that could be because of a lack of data?
Unraveling Potential Sex‐Specific Effects of Cardiovascular Medications on Longevity Using Mendelian Randomization 2023
This first MR study concerning sex‐specific effects of genetically mimicked cardiovascular medications on longevity, equating to drug use in primary prevention to enhance lifespan, found an existing lipid‐lowering drug (PCSK9 inhibitors) and 2 antihypertensives (β‐blockers and calcium channel blockers) were associated with longer lifespan, particularly in men. Potential lipid‐lowering therapy targeting APOC3, LPL, or possibly LDLR and metformin was associated with longer lifespan in both sexes, with targeting LPL possibly having a greater effect in men than women. Conversely, statins, ezetimibe, and ACE inhibitors were less clearly related to lifespan in women or men. All existing or potential lipid‐lowering therapies affected IHD risk, diabetes risk, or both as expected, except ACE inhibitors and β‐blockers. Apart from highlighting the potential for repurposing to promote longevity, our findings highlight the importance of accounting for sex in drug development and prescription.
5 Likes
Bicep
#20
I’d like to see them put in alpha cyclodextrin. Since it’s mice and they don’t die from heart disease it may not show any benefit, but it would be fun to see if it causes harm. It turns into short chain fatty acids on the way out whether it ties something up or not.
1 Like
Bicep
#22
oops, yeah that’s dumber yet. Not as expensive though.
1 Like
adssx
#23
Yes, if we’re sure that what doesn’t work on C. elegans won’t work on humans, then we can screen thousands of compounds on worms (that’s their goal: “assess 1,000,000 longevity interventions in 5 years”) and move the successful ones to rodents and then… dogs? and then humans?
3 Likes
Neo
#24
@DeStrider I don’t think we can say that.
Perhaps one can say that that will be the case of lot of the time, but there are probably a lot of things that could help humans even if they won’t help worms.
2 Likes
Things that are toxins for worms are most likely toxic for people.
As for compounds that have no effect, I think you are correct that some, like cholesterol lowering drugs, may have no benefits for worms but are useful for humans.
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adssx
#26
Opposite view: Genetic insights into the association of statin and newer nonstatin drug target genes with human longevity: a Mendelian randomization analysis 2023
“The lipid-lowering variants of HMGCR, PCKS9, LPL, and APOB were associated with longer lifespans but did not causally increase extreme longevity. No statistical evidence was detected to support an association between NPC1L1 and lifespan.”
But contrary to the other MR study above, they didn’t look at sex differences. If Ezetimibe has any effect, it might be on males only. I’ll contact Ora Biomedical to see if we can try BA+EZE…
3 Likes
adssx
#27
Ora Biomedical’s answer about compounds not listed yet on their website such as semaglutide, selegiline or Urolithin A:
It looks like the requested small molecules are not in our sponsorship drug library. It would still be possible to sponsor these intervention tests through a custom contract. Purchasing and shipping compounds from a reputable research chemical supplier would be part of the sponsorship charge since we do not currently have the compounds in stock. We also recommend testing compounds across a dose response with these contracts.
So basically instead of paying $100 you pay drug cost + 3 x $100 (three different doses).
I don’t get why they need 3 doses for these and not for the ones listed. I’ll ask…
In the meantime, I’ve already sponsored:
- Canagliflozin
- Dapagliflozin
- Empagliflozin
- Telmisartan
- Ezetimibe
10 Likes
@adssx Thanks for sponsoring these. Those are all great choices. I’m interested in the results! Please post them here when you get them. 
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adssx
#29
Thanks. They told me my results are expected in 6 weeks. I’ll post them here of course
8 Likes
BTW, do we have any results yet?
From what I see, many people here sponsored some interventions - how long it takes to get results?
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