11 replies to this topic

[smithx]

In mice:

Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain-of-activity mouse model presents with a premature aging-like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging, and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75-week-old) female C57BL/6 mice with a Cdc42 activity-specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan. Moreover, aged CASIN-treated animals displayed a youthful level of the aging-associated cytokines IL-1β, IL-1α, and INFγ in serum and a significantly younger epigenetic clock as based on DNA methylation levels in blood cells. Overall, our data show that systemic administration of CASIN to reduce Cdc42 activity in aged mice extends murine lifespan.

 

https://onlinelibrar...1111/acel.13208

 

Look at the last graphic: biological (epigenetic) age was significantly reversed.

 

 

This is very bleeding edge, but the compound is available:
https://www.xcessbio...b5f6cb6b6&_ss=r

And it's got better data than some other things that were posted recently: it works on mice, not just in vitro.

[floret]

Nice find. How would it be administered?

 

Molecular weight is 306.40, which is fairly small.

[smithx]

Nice find. How would it be administered?

 

Molecular weight is 306.40, which is fairly small.

 

If you read the study, it was by injection.

[floret]

I looked up the price--the stuff is not cheap. Appears safe, though!

[smithx]

Another paper on CASIN:

https://www.nature.c...536-022-00275-y

"... Here, we demonstrate that after a short systemic treatment with a specific inhibitor of the small RhoGTPase Cdc42 (CASIN), transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. In detail, we show that systemic CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells...."

 

 

About dosing: if we were to use the body surface area method (see: https://www.ncbi.nlm...s/PMC4804402/) then we would divide the mouse dose by 12.3. So we get about 2mg/Kg as the dose.

This is the company that supplied the CASIN used in the paper:
https://www.xcessbio...b5f6cb6b6&_ss=r
 

They may have lower prices for larger quantities, but if we use their price of $850 for 100mg, then a 70Kg (154lb) person would need 140mg per dose for $1190 per dose. If the protocol in the paper were replicated, the total cost would be $4760, which seems like not that high a price to pay for cutting your epigenetic age in half!

 

Of course this is a substance never tested on humans (as far as we know) and there's only a couple of mouse studies so far, but it doesn't seem to be something that's completely out of reach.

 

Edited by smithx, 20 May 2024 - 12:08 AM.

[floret]

Agreed. I'd gladly spend that amount of money on a proven treatment that cut my age in half--if I had that money to begin with.

[Chemically_Charmed]

Another paper on CASIN:

https://www.nature.c...536-022-00275-y

 

About dosing: if we were to use the body surface area method (see: https://www.ncbi.nlm...s/PMC4804402/) then we would divide the mouse dose by 12.3. So we get about 2mg/Kg as the dose.

This is the company that supplied the CASIN used in the paper:
https://www.xcessbio...b5f6cb6b6&_ss=r
 

They may have lower prices for larger quantities, but if we use their price of $850 for 100mg, then a 70Kg (154lb) person would need 140mg per dose for $1190 per dose. If the protocol in the paper were replicated, the total cost would be $4760, which seems like not that high a price to pay for cutting your epigenetic age in half!

 

Of course this is a substance never tested on humans (as far as we know) and there's only a couple of mouse studies so far, but it doesn't seem to be something that's completely out of reach.

 

I can get this for much cheaper. I will buy some and try it out.

[Chemically_Charmed]

Another paper on CASIN:

https://www.nature.c...536-022-00275-y

 

About dosing: if we were to use the body surface area method (see: https://www.ncbi.nlm...s/PMC4804402/) then we would divide the mouse dose by 12.3. So we get about 2mg/Kg as the dose.

This is the company that supplied the CASIN used in the paper:
https://www.xcessbio...b5f6cb6b6&_ss=r
 

They may have lower prices for larger quantities, but if we use their price of $850 for 100mg, then a 70Kg (154lb) person would need 140mg per dose for $1190 per dose. If the protocol in the paper were replicated, the total cost would be $4760, which seems like not that high a price to pay for cutting your epigenetic age in half!

 

Of course this is a substance never tested on humans (as far as we know) and there's only a couple of mouse studies so far, but it doesn't seem to be something that's completely out of reach.

 

"Applying this C57BL/6-trained DNA methylation marker panel to blood cells from aged animals treated with CASIN 9 weeks after treatment, we observed that epigenetic age predictions did not correlate anymore to the chronological age as in aged control animals, but resulted in a biological age prediction that was on average 9 weeks younger than their chronological age (Figure 1i)"

 

It said the rats that were 9 weeks younger when they were 80 weeks old not 50%
 

[adamh]

Yes, this must be approached with healthy skepticism. How many times have we head of some wonder drug that upon closer inspection turns out to be less than expected and often with nasty side effects? Already the claim that it cut effective age in half has been challenged and said it was only 9/80 improvement which is good but not 50% and we don't know the side effects or if it even works at all in humans. If the effect is 11% in mice it might be 1% in humans or nothing at all. Short lived species often show the greatest benefit from these things

 

If it gave even a 10% improvement in overall health and healthy lifespan, then its worth a lot assuming the sides aren't too terrible. A few thousand is a trifle when talking about years more of healthy life vs getting sick and dying earlier. The 50% improvement is likely a flash in the pan but would be worth millions if true.

 

When/if these wonder drugs come out they will be super expensive at first but with mass production and with many doctors wanting to get in on the cash grab, competition will force the price down. But, greatly extended lifespan may cause more disruption than what we speculate about ai.

[Daniel Cooper]

I looked up the price--the stuff is not cheap. Appears safe, though!

 

Has CASIN be trialed in humans? Is there any human safety data at all?

[smithx]

I can get this for much cheaper. I will buy some and try it out.

 

Where can you get it cheaper?

"Applying this C57BL/6-trained DNA methylation marker panel to blood cells from aged animals treated with CASIN 9 weeks after treatment, we observed that epigenetic age predictions did not correlate anymore to the chronological age as in aged control animals, but resulted in a biological age prediction that was on average 9 weeks younger than their chronological age (Figure 1i)"

 

It said the rats that were 9 weeks younger when they were 80 weeks old not 50%
 

 

Good catch! I was looking at the graphs and obviously hadn't read the text as carefully as I should have.
 

[QuestforLife]

Max lifespan increase looks more impressive than epigenetic age reduction (eyeballing the LS curve, maybe 19% vs about 11%). Kinda interesting that epigenetic age reduction was 9 weeks taken 9 weeks after the treatment, though. Makes you wonder what the delta would have looked like at other time points, and what the result would be from multiple treatments.

 

I've been interested in ROCK inhibitors for a long time, so I'll keep an eye on this thread.