A Small Lifespan Study of Combined Interventions

My attention was drawn recently to a small mouse life span study run by one of the groups that has been in the longevity community for a while now. It is interesting for testing combinations of interventions that have in the past been demonstrated to modestly slow aging in mice (such as rapamycin), or modestly improve aspects of cell function in old tissues (such as nicotinamide mononucleotide). Combinatorial studies are rare in academia and industry, for reasons that have a lot to do with (a) the perverse incentives produced by the existence of intellectual property, in that the rights to use specific interventions can be owned, granted, refused and (b) the way in which the huge cost of regulatory approval determines which projects that can be successfully funded, typically only those in which patents grant a monopoly on use.

The results are much as one might expect, given the interventions chosen, in that most of the combinations did little to nothing to mouse survival and life span. The only one that appears to have an effect is the use of C60 - an intervention that, you might recall, has a checkered history in animal studies. The most recent data, from Ichor Therapeutics and others, who spent some years working with C60, is that it is not a useful intervention in the matter of modestly slowing aging.

Unfortunately, this study did not control for inadvertent calorie restriction. When an intervention makes mice feel ill, they will eat less. Mouse weight is a sensitive barometer of mouse well-being. Even minor degrees of calorie restriction can extend mouse life span, distorting the effects of interventions. This is one of the reasons why rigorous studies, such as those conducted by the Interventions Testing Program, tend to find no effect when repeating earlier studies in which an intervention was claimed to modestly slow aging. Sadly, this means that positive outcomes here don't have all that much weight, and it is possible that some of the neutral outcomes are actually poor outcomes.

Bucky Labs Longevity Study

Our mouse longevity study completed with interesting results. Frankly, we did not know what to expect. We tested our products and other promising substances on 245 interbred male C57BL/6 mice. We started the interventions when mice were 300 days old (about 50 in human yrs). Caveats: the sample sizes were very small, optimal dosages were guesses, and we did not weigh the mice - so some effects may be from dietary restriction, etc.

1 C60 99.95 Olive Oil 10%
2 C60 in MCT oil 10%
4 cycloastragenol, NMN, fisetin, icariin, berberine, cistanche, AFA algae
5 exosomes, klotho, FOXO4-DRI, gdf11, epitalon
6 rapamycin, Azithromycin, metformin, NMN, spermidine, echinacea
7 NMN, fisetin, C60
8 RG7834, DHEA, berberine, fisetin, NMN
9 berberine, BHB, NMN, ALA, cycloastragenol, spermidine, DHEA, rhodiola, fisetin, icariin, echinacea, cistanche
10 rapamycin, metformin, aspirin, niacin, RG7834, spermidine, FOXO4-DRI, gdf11
11 centrophenoxine, exosomes, fisetin, metformin
12 double dose fisetin, double NMN, double cycloastragenol
13 klotho, RG7834, spermidine
16 gdf11
17 spermidine
18 double NMN, double berberine, double centrophenoxine, double cycloastragenol, double fisetin
20 NMN, ALA, pterostilbene, cycloastragenol, centrophenoxine, spermidine, DHEA, melatonin, rhodiola, luteolin, fisetin, icariin, echinacea, cistanche, carnitine
21 double fisetin, double NMN, double berberine, NAC, DHEA, echinacea, cistanche

The best intervention was Intervention 1 (red line), C60 Olive Oil (the mouse feed was supplemented with about 10% C60 in organic olive oil). This group also had the largest number of mice (16), so the confidence that something real is happening is greatest with this intervention. The next best group was Intervention 9 (NMN, spermidine, berberine, BHB, ALA, cycloastragenol, dhea, rhodiola, fisetin, icariin, echinacea, cistanche). The following next best interventions are clustered closely around the control, so no conclusions should be made. Surprising that the poorest performer was Intervention #20 (NMN, ALA, pterostilbene, cycloastragenol, centrophenoxine, spermidine, DHEA, melatonin, rhodiola, luteolin, fisetin, icariin, echinacea, cistanche, carnitine) which is similar to the 2nd best performer. Also, Intervention #8 (RG7834, DHEA, berberine, fisetin, NMN) did not do well.

The results with our peptides/proteins did not appear to result in any significant longevity increases. Also, surprising was that the interventions with rapamycin did not appear to produce significant improvements. Lastly, ours is the first lifespan study to investigate C60 with an alternative lipid, we tried MCT oil (basically coconut), and there was no lifespan improvement.


So a seller of C60, in Arizona. #1 conflict of interest

Did they have any biology degree, research training, lab experience, animal handling training or is this some yahoo's garage setup in order to market more supplements?

Their website does not publish any of the negative findings of C60 where it failed to extend lifespan vs water, or the light induced toxicity.

Eyes could not roll any harder.

Posted by: john at September 26th, 2022 5:07 PM

Well that's depressing. Hitting it at several angles as many of us do - with no positive results.

Posted by: august33 at September 26th, 2022 10:06 PM

Is there any reference, pubblication, evidence based link?

Posted by: Gianfranco at September 27th, 2022 3:49 AM

If rapamycin and NMN do extend mice lifespan when used as single agents, what is the presumed mechanism behind their failure to work when administered in combination with other drugs?

Posted by: Barbara T. at September 27th, 2022 1:38 PM

C60 was debunked years ago.

Posted by: Anonamoose at September 27th, 2022 2:36 PM

I took a few bottles of C60 around 2015. Regret that a lot in retrospect. Sticking to plain aspirin and GlyNAC for what it's worth.

Posted by: arren brandt at September 28th, 2022 11:01 AM
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