- We’ve been looking at biomarkers in a very limiting way: There is a new biomarker used to diagnose Parkinson’s based on lipids in sebum. Incredibly cheap and easy way of doing it, based on one nurse’s ability to smell Parkinson’s patients. Similar to that, we as a field could be a bit more adventurous about the types of things that we consider as a biomarker.
Collecting samples from humans is impractical unless it’s blood, what are some other sample modalities?
- Maybe non or minimally invasive things like skin biopsy, urine, saliva. Problem is that it’s hard to get high throughput data for the less used modalities. That might be an opening for new tools that are able to do that. To bring something into the clinic, it needs to be high-throughput and easily measurable, and also standardized so we can compare between different studies. So we can do 1000s of samples for large studies and then clinical use. That is a challenge that we should be working on, so we can get bigger databases. There’s a focus on discovering biomarkers, but not much focus on making those measurements affordable and available in high-throughput fashion.
What should government funded research be doing with future centenarians to track them now? What does Nir Barzilai wish he would have done before starting the original study on centenarians with current tools?
- Nir Barzilai, Thomas Perls, AFAR, Regeneron are together starting a project with the aim to recruit the next 10000 supercentenarians, and get all the data (whole genome sequencing, electronic medical record,…) from them. They are also recruiting their offspring, because when looking at supercentenarians, you are never sure whether you are looking at what enabled them to live that long, or what will kill them in a year, because they’re at the end of their life. But offsprings should be a great treasure trove of the right data (for example IGF and HDL levels, which proteins they have even in youth and are inherited, or which special proteins they have, etc.).
Do methylome clocks on the offspring of supercentenarians look better than the age matched controls?
- They are just studying that, and it seems that they actually fall between the supercentenarians and controls. But supercentenarians are older, so the question is which methylation patterns are inherited – it is possible that the methylation patterns are inherited, so there’s a lot of work to do on the biology of methylation and not only the clocks.
Do supercentenarians have a shared mechanism or are there multiple mechanisms how to get there?
- We don’t know yet, but we might be able to see soon with the increasing amount of data that we run through models. The more data we have the more needles in the haystack. However even now, if we put the genetic differences among supercentenarians into pathways, they are really telling – insulin IGF pathway, mTOR pathway, AMPK pathway, sirtuin pathway. So it’s probably all there, we just need to know what to ask. Pathway analysis is a key to this, we cannot look at single proteins as biomarkers, because there are not statistically significant differences most of the time. But when we look at it on the systemic level, and take 50 proteins that are involved in the exact same biochemical pathway and they all shift in the same direction, then the pathway becomes really significant as a whole.