Hi! Thanks for asking this question! Here is Science Writer for SENS Research Foundation Michael Rae's answer: "There is a lot of evidence that damaged ECM doesn't support cell function properly, so transplanting healthy, young cells into an old animal's ECM is likely to be hampered by either the lack of some kind of signaling that young, intact ECM provides, or by abnormal signaling that is produced by an old, damaged ECM. So far we only know a fraction of what those signals are. The best way to deal with this problem is to directly repair the damaged ECM itself; if we do that, the rejuvenated ECM will provide the appropriate youthful signals with no further action on our part. However, you can imagine instead that either providing signaling factors that are missing in old ECM or blocking (with a drug or an antibody) signaling factors that are present in damaged ECM could help improve cell transplantation even if we haven't yet mastered the repair of old ECM. That's what Dr. Clark was getting at. Exactly what those signaling factors are or how we would either stimulate, supplement, or block them is something we can only explore as Dr. Clark's research proceeds and we understand better what kind of damage the ECM is suffering with age and then look to see what signaling effects that damaged ECM have on cells, and how. "

@@SENSRF So as you say : "blocking (with a drug or an antibody) signaling factors that are present in damaged ECM" will be the method for persistence for an an Exogenous youthful cell therapy. Dr Jonathan Clark has a big task to inhibit the signal molecules from one set of cells whilst promote the signal molecules from another set. I am not sure how what proposal that is, that would be worth discussing with Dr Jonathan Clark.