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Clonal expansion of hematopoietic precursors is something that we see generally as people age [1]. Rather than positing a beneficial role for clonal expansion of cytotoxic T cells, my null hypothesis would be that this clonal expansion is simply another marker of aging.

1 = https://en.wikipedia.org/wiki/Clonal_hematopoiesis




Very possible and future experiments should probe this hypothesis too. We should never forget that the very beginnings of immunotherapy were paradoxes themselves (e.g. infecting someone with a disease to control cancer). Our immune system, like many other complex non-linear systems, have been known to behave unpredictably at local levels while behaving predictably at a global level. If you have not already read it, this is a fascinating review of the paradoxical progress of modern immunotherapy (cancer centric) - https://www.sciencedirect.com/science/article/pii/S235230421...


That disregards the possibility that certain clonal expansions could be beneficial. General clonal expansion may be correlated with aging, but some clonal expansion may concern extended longevity.


It doesn’t disregard that hypothesis. The hypothesis is interesting. But it’s not my default hypothesis; it’s the alternative hypothesis.




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