Neuroprotective effects of Canagliflozin: lessons from aged genetically diverse mice

A new study out from Richard Miller’s group (the guy who leads the NIA’s ITP program testing compounds for anti-aging.)

Interestingly, just as with the study that showed lifespan increase only for males, this study also saw improvement in neurological function only in males.

Remarkably, Cana treatment improved exploratory and locomotor activity of 30-month-old male but not female mice. Taken together, our findings demonstrate sex-specific neuroprotective effects of Cana treatment, suggesting its application for the potential treatment of neurodegenerative diseases.

Full Paper Below:

2022.01.27.478017v1.full.pdf (2.0 MB)


like how males benefit more from acarbose?

There is a slightly better result in males for acarbose (11% lifespan improvement in males vs. 9% in females) - but the difference for Canagliflozin in males is much much better (14% lifespan increase for males vs. 0% increase for females).

Do Cana & Acarbose work similarly? I use Metformin and it feels like using three glucose disposal agents every day is “gilding the lily” a bit.

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No - Cana works in the kidneys, Acarbose in the upper intestine … so different actions, different drug targets, but the effect is similar in that they lower glucose spikes.

I agree, I don’t think you want to use all three at the same time.

There are pros and cons to each drug… Metformin is the most proven, and safest - but least effect in terms of mouse longevity, but also lower side effect profile. Cana is a newer drug, still being understood I think. Acarbose older - but with bad side effects (gas) common.

I have all three - but tend to mostly rely on low dose empaglflozin (another SGLT2 inhibitor), with occasional acarbose use, and rarely some metformin if I’m out of Emp.

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I’m not a doctor. But I do wonder if a lower dose of each of them when co-administered would be better. Less risks of UTI and fatigue from SGLT-2, less bloating from acarbose, and less exercise intereference for metformin.


Given that females of species tend to live longer in general, I’ve wondered how many of these interventions bring males to female levels as opposed to making males live longer than females.

Mechanistically, I find this way of thinking easiest in the case of 17-alphaestradiol.

Still not sure how acarbose benefits males more. Perhaps it mediates the release of some androgenic hormones? No idea.

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Another approach i think might be to alternate all three (i.e. pulsed, periodic dosing) … One week sglt2 inhibitor, then one week Aca, then one week metformin…

Of course - what we really need are animal and then human trials testing out these different types of dosing protocols, to see what is the most effective.

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Source for 11%? Another source I have says ~22%

I think it was the 2013 itp study results. See here.

Does anyone have a source for 17- alpha estradiol ?

All you need to do is find a friend who works at or runs a chemistry or biology lab / small company or in a school/college/university academic department that deals with research chemicals or biologicals. Check your account for possible contacts…

The chemicals companies that sell these typically have a statement like that below:

Please note that our products are for research use only and cannot be delivered to private individuals and addresses, but only to authorized institutions and businesses.

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I’d have attempted getting it, but I first need to confirm what dosage is needed. I can’t seem to find any data or anecdotal reports about this.

If and when i try 17 alpha estradiol i would start at the doses used for beta estradiol in women, and the slowly increasing the dose. See our page on 17 alpha estradiol and the clinical trials papers. Very high doses have been tried with no side effects so starting low at the same levels as women using beta version of the molecule seems likely to be a good start. If anything it my be low, but better to be safe.

Both 17 alpha and beta estradiol is currently in the product given to women (its a “chiral molecule”, and the Beta version of estradiol is the feminizing hormone that women need). So this molecule has been used in women (perhaps 5% to 10% of the total estradiol) for the past 20 plus years… I think.

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