Biology of Aging and Clinical Studies We'd Like to See Done

The more we dive into the use of Rapamycin and other mTOR inhibitors, the more we identify the many unanswered questions around how best to optimize the use of the drug for longevity, and how best to translate the animal research into truly useable knowledge (translational research) for human use, and clinical application.

So - I’m creating this thread for everyone’s use, as a way for us to “crowdsource” some biology of aging research ideas in areas that we have a unique perspective on; how we can best translate the current lab / animal science into something that we is much more useable and beneficial for people using these medications. I’m thinking this might be a way to spur on an increase in translational biology of aging research that is desperately needed right now. I also find it helpful to identify clearly where the gaps are in our knowledge, which is important as we use these medications and track the impact on our biological / blood measurements and make adjustments.

When we start getting more ideas here - I’ll start publicizing it to the mouse/rapamycin and geroscience researchers and perhaps our ideas from our “in the trenches” use of rapamycin, can help stimulate more ideas and studies for the researchers to focus on and get funding for.

With the vast amount of funding starting to flow into biology of aging ($1 Billion per year just from the Saudi Government / MBS and friends) - it seems that since we are the closes of anyone to translating all the research into use, that perhaps we can help drive the research by pointing out key areas of missing data that we think needs to be done.

So - Please post your ideas for studies here. Keep each post to a single study topic area so that we can also effectively “vote” on each research concept by “liking” the post. Then the researchers can also see what we think might be the priority of each of these issues, as they consider them and also when they try to justify the study to their IRB, and the funding review boards.

I’m thinking (but I’m open to feedback from others) that a general layout for the Study Idea Proposals would be based on the general outline that is being used in the VitaDAO Funding Proposals - see example of successful VitaDAO Longevity proposal here. Of course, my rationale is that by doing this we make the use of our ideas more easily adopted by researchers who could make proposals to groups like VitaDAO or the Impetus Grants.

So - to keep it simple, something like this:

Summary of Study: A general overview of the study
Key Problem Study Would Address: (what is the exact problem that we are encountering that drives the need for this study)
Opportunities: Additional benefits of the study that could be realized.

So - I’ll start with an idea that prompted this thread - with a rough draft of the approach. What got me thinking about this need was this discussion thread were the issue of rapamycin / rapalog administration methods came up: Rapamycin Method of Delivery, Considerations

Summary of Study: Rapalog Biodistribution Study: The NIA ITP program has seen fantastic success with simple studies of different dosing, and dosing sequences, of rapamycin in mice, providing life extension benefits of upwards of 26%. Oral rapamycin (by tablet) has a specific biodistribution profile but I have not seen a great deal of research on the exact bio distribution profile of rapamycin (rapamune or generics) so we do not know what organs and tissues benefit most from the rapamycin use. We also don’t know the different biodistribution profiles of the rapalogs and the different administration methods; oral tablet vs. liquid, injection (subcutaneous vs. IP/IM), and the benefits/ tradeoffs of each approach. Without this knowledge we cannot optimize the use of rapamycin in humans. This study would try to address this problem.

Specific Study ideas (in rough order of difficulty/cost):

  • Blood Brain Barrier test: What difference is there in biodistribution in the different drugs / administration methods.
  • Short term biodistribution study of all rapalogs - rapamycin, everolimus, tacrolimus - oral tablet, oral solution, ip/im injection, iv injection. What difference is there in biodistribution in the different drugs / administration methods.
  • Longer Term Biodistribution & benefits Study - longer study to see the difference in benefits seen from the different drugs and administration methods
  • Functional Testing: What are the functional benefits of the different rapalogs and admin vectors - measured in terms of standard memory/cognitive, and exercise capacity tests.
  • Lifespan: What are the lifespan benefits of the different rapalogs and admin vectors in terms of longevity speaking. Do combinations outperform single drug approaches?

Key Problem Study Would Address: People are seeking to use rapamycin for longevity, but we lack the precise knowledge of which organ rapamycin is reaching, which organs or tissues it is not reaching, and which administration vector provides the best delivery mechanism for each organ or tissue type for maximum longevity benefits. There is some research that suggests, for example, that everolimus may pass through the blood brain barrier more easily and effectively than rapamycin, so periodically dosing with everolimus and rapamycin may provide unique benefits.

Opportunities: Additional benefits of the study that could be realized.

  • Identify administration approaches with rapamycin and rapalogs that can further optimize the longevity benefits on an organ / tissue specific basis.
  • Increase maximum lifespan by using multiple MTORC inhibitors in a dose schedule and/or administration approaches (oral, IP/IM injection / IV injection).