Feb. 28th Cutoff For NIA ITP Aging Drug Submissions - Ideas for New Testing?

Does anyone have any ideas for compounds, or combinations, that they are considering sending in to the ITP program for testing (or have already sent in?).

I’m wondering if this new discovery might warrant a proposal? Drug Revitalizing Old Blood May Slow Aging (Anakinra / Kineret)

Application Instructions

The submission deadline occurs once per year on the last weekday in February.
The next deadline is Tuesday, Feb. 28, 2023.
See Application Instructions and use the Application Form (Word, 32K).

Request for Proposals

NIA seeks proposals for agents to be included in Stage I testing to determine effects on lifespan. Interventions can include, but are not limited to, pharmaceuticals, nutraceuticals, dietary supplements, plant extracts, hormones, peptides, amino acids, chelators, redox agents, and mixtures of compounds. All test agents must be able to be stably incorporated into rodent chow. Applicants can be individuals, nonprofit or academic groups, or commercial entities. NIA is responsible for the costs of the testing through grants to the three testing sites.

Applications that do not conform to this requirement may be returned without review. Although there is no length limit, most applications are between five and 10 pages long.

Examples of Successful Proposals

Example 1 – MIF098 (PDF, 296 KB)
Example 2 – Resveratrol (PDF, 200 KB)
Example 3 – Sulindac (Word, 178 KB)
Example 4 – mTOR Inhibitors (Word, 227 KB)

Application Instructions:

More information: ITP | National Institute on Aging

Related, Good Video on the NIA ITP Program: Drugs That Slow Aging in Mice: the NIA Interventions Testing Program

The initial Rapamycin ITP Suggestion for Testing:

RapamycinITPexample_4_-_mtor_inhibitors.pdf (227.1 KB)


Rapamycin + A potent cholesterol reduction drug like a statin + Acarbose

To minimize the negative effects of Rapamycin on cholesterol (statin) and blood sugar (acarbose).

However, mice don’t die of CVD, so maybe save it for the human trials. :wink:

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Definitely warrants a proposal. Is it injectable only though?

Has Rapa + Canagliflozin been tested yet? Seems like that would be a good one to test since both show positive results and Acarbose is difficult to take for some people

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It’d also be nice to see a NAC + Glycine or NAC + Glycine + Rapamycin trial.

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I just submitted a very brief proposal to the ITP. My idea is to test rapamycin at a dosing schedule interval that minimizes potential side effects. Below is the main part of my proposal:

Background and Rationale

Rapamycin has been the most successful intervention tested at the ITP. It has been found to extend life span of mice in the ITP both in isolation and when combined with other interventions. As a result of the success of rapamycin, many people have begun to experiment with taking it for longevity. Yet the optimal dosing regimen for rapamycin for longevity purposes is unknown. Therefore, it is urgent to find out what is likely to be the optimal dosing regimen for longevity.

Different dosing regimens of rapamycin have been tested in the ITP, but this has only been done along one axis (the total daily dose) but not among a potentially equally important axis, which is the frequency of dosing.

Rapamycin has increased life span at different doses and the longevity benefits appear to be somewhat synergistic when rapamycin is given along with metformin or acarbose. Metformin and acarbose can both act to reduce blood glucose but chronic rapamycin exposure can induce insulin resistance which consequently results in elevated blood glucose levels that are harmful for aging. Thus, it is not surprising that they act somewhat synergistically with rapamycin since they have potential to reduce the negative effects of rapamycin on insulin sensitivity and blood glucose.

As an alternative to administering metformin or acarbose with rapamycin to minimize the harm rapamycin has on blood glucose levels, it may be possible to modify the schedule of rapamycin intake to minimize the negative effects on blood glucose levels while not interfering much with the longevity benefits. Here it is important to note that the main benefits of rapamycin for longevity are thought to derive from inhibition of mTORC1, but rapamycin inhibits mTORC1 strongly and directly.

While rapamycin does not inhibit mTORC2 directly and therefore short term exposure to rapamycin does not significantly inhibit mTORC2, chronic exposure to rapamycin can lead to indirect inhibition of mTORC2 by interference with the assembly of mTORC2. (Ref.1) This may cause problems since many of the side effects of rapamycin are thought to derive from mTORC2 inhibition. As an example, inhibition of mTORC2 by rapamycin has been found to be required to induce insulin resistance in the liver of mice exposed to rapamycin. (Ref. 2)

Given that most of the potential longevity benefits of rapamycin are attributed to mTORC1 inhibition while most of the potential side effects are attributed mainly to mTORC2 inhibition, it is reasonable to try to modify the rapamycin dosing schedule in a way to maximize mTORC1 inhibition while minimizing mTORC2 inhibition. This is most certainly possible to some degree by simply modifying the frequency of dosing.

In a 2012 study published in the USA the authors set out to determine the most frequent rapamycin dosing schedule that does not negatively effect blood glucose levels. They gave rapamycin to mice at a dose of 2 mg/kg body weight either daily, every 3 days or every 5 days. When given daily or every 3 days it had negative effects on glucose tolerance but this was not seen when it was given every 5 days. (Ref 3) These results suggest that giving rapamycin every 5 days may be a good way to maximize the inhibition of mTORC1 while minimizing negative effects due to mTORC2 inhibition. Hence this intermittent method of administration may be worth testing for longevity.

Note that this method makes sense if we consider the plasma half life of rapamycin (about 15 hours in mice). At that half-life and administration every 5 days it’s about 8 half lives between doses. That should be enough to get blood levels to almost zero for a short while between doses which, in turn, helps prevent the chronic exposure that ultimately leads to mTORC2 inhibition.

Suggested Treatment Protocol

Given the above results I suggest testing rapamycin by giving it to mice in their food every five days. Since rapamycin has already been found to extend lifespan in the ITP at doses of 14.7 and 42 ppm daily, I suggest testing it at the highest dose, or 42 ppm administered once every 5 days. This would result in an average daily dose of 8.4 ppm, which is on average around half of the lower doses that were found to be beneficial in the ITP studies. Hopefully, that will give some longevity benefits with minimal negative effects from mTORC2 inhibition. Treatment would optimally be initiated early in adulthood (4-6 months) and continued throughout life.

Ref 1:
Mol Cell. 2006 Apr 21;22(2):159-68. doi: 10.1016/j.molcel.2006.03.029. Epub 2006 Apr 6.
Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB
PMID: 16603397

Ref 2:
Science. 2012 Mar 30;335(6076):1638-43. doi: 10.1126/science.1215135.
Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity
PMID: 22461615

Ref 3:
Aging Cell. 2016 Feb;15(1):28-38. doi: 10.1111/acel.12405. Epub 2015 Oct 13.
Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system
PMID: 26463117


They should test selegiline.

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Interesting… yes Deprenyl / Selegiline : Deprenyl - Anti-Aging Drug Proven Effective in Dogs

I also wonder if it might be possible to get copies of all the submissions… would be interesting to see what people are recommending. perhaps a “freedom of information” request would get it? Anyone here have any experience with those?

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I believe Richard Miller will help you out if you ask him.

Well done and thank you

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If no one has submitted for it yet maybe a few of us could put together a proposal


I know some people were thinking of making a proposal for testing everolimus, because it’s more selective for mTORC1 than rapamycin. While I think that is a good idea I personally would rather see more research on the optimal use of rapamycin. The reason being that everolimus is super expensive. It would cost thousands of dollar of month to take so very few people would afford it.

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Given that the primary advocates for the drug, Kenichi Kitani and Joseph Knoll, have passed away, it may be necessary to do that.

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