You mentioned it’s easier to do things when you’re healthier, and we know that exercise itself has a geroprotective effect. So it stands to reason that the eventual beneficial effects of an intervention could be split into first order and second order causes (like the biological effect of the intervention, and how it made you feel and perhaps exercise more, etc.). When it comes to having to rank interventions to rank first order effects, is there any system in place to normalize or tease out these two potentially compounding components? By normalizing based on mobility changes or anything like that?
- That’s a sort of question that a trialist would be more able to answer but I can speculate a little. You track what’s going on and look for secondary effects and if they feed back, they can be treated as confounders of the primary outcome. And there are actually graphical and mathematical ways to display that and tell you whether something is significant in terms of relating the intervention to the outcome or if it’s a modifier of the outcome..
Nir, is that kind of analysis planned for the TAME trial, to normalize for the mobility increases and things like that?
- Absolutely, 25% of the budget is a grant from the NIA to take all the biomarkers from TAME and make sense of them. Because what we’re missing mainly is not biomarkers, but the knowledge about which biomarkers are changing with aging and which to therefore track, so we can look for changes in shorter periods than years-long trials measuring outcomes. You have to plan it very carefully and do all the analysis to really understand what’s going on.
- You’re raising a very good point though, because what you’d like to get from intervention is for people to be able to do more of the things that have beneficial effects. You want to have some ways to increase their independence.
Who are the other champions within the NIA who are supporting this direction of research? Or are there any opponents?
- We’re all in this together, we collaborate quite a lot. There are multiple divisions (geriatrics and clinical gerontology, behavioral and social research, neuroscience research). We also work together with other NIH institutes. Pretty much every other institute is now paying attention to aging as a parameter. And there’s also a NIH wide approach to include older people in clinical trials and research. There is not really opposition, more enthusiasm, with due caution because of the problems associated with asking older people to participate in clinical trials – there are serious ethical concerns in some cases when they are cognitively impaired.
Is anybody at the NIA doing work specifically with imaging data in relation to predicting aging biomarkers?
- Yes, there’s a lot of work being done with imaging technologies. We actually had a project for imaging aging, and we do have similar programs in the area of validating biomarkers for clinical trials. For example, cell painting that reveals about a 1000 of cellular phenotypes, cryo electron microscopy, work on chromatin structure, and imaging from dexa scans.
If you can pick from the entire universe of biomarkers, what was the most predictive of the rate of aging and future longevity?
- I don’t have one favorite biomarker. There are many projects going in the right direction, including the work done by Steve Horvath and Morgan Levine.
How can people learn about new grants from the NIA?
- Funding opportunities are decided by council advisors in January, May, and September and visible on the NIA website in the recordings of those meetings. The next meeting is in mid May. Watch the website.
- You can also file a request for information (RFI) with NIA’s abbreviation to look at funded work in the past.
- You can contact anybody at NIH through firstname.lastname@example.org.
Are there going to be any changes in the structure of NIA or NIH that are relevant that you can talk about?
- Expanding focus on health disparities in relation to aging and increased focus on research in human populations. We have around 70 grants with human populations. The technology to do basic research with humans is available, so we should be moving that way and are trying to do so.
What challenge would you like to see more work to be done on?
- Widening our understanding of basic biology of aging in the human population. This includes widening and diversifying the human demographics we study and finding promising intermediary candidates between mice and humans to study aging.
What does NIA want more of, what can people help with?
- Public private partnerships: partnering with industry on projects of common interests.