There is an important and ongoing longitudinal study of the drug...

There is an important and ongoing longitudinal study of the drug rapamycin in dogs (“The Dog Aging Study”) that shows rapamycin treatment improves ejection fraction. Rapamycin acts on the mTOR nutrient sensing pathway (which becomes dysregulated with age), stimulates stem cells and is a powerful antinflammatory. PPS shares the latter two effects, so it’s interesting they both seem to help EF.

Rapamycin has improved lifespan in all animal models in which it has been tried, and is widely considered an anti-aging drug. The root cause of all the factors in your EF diagram is aging, so it’s not surprising if an “anti-aging” drug improves EF. By hitting a single cause it hits multiple secondary and proximate causes.

I think about pentosan in these terms. It also hits a number of different factors in aging, so I wonder about its potential to treat other diseases of aging, beyond OA. I should remark I take rapamycin for these reasons, but it did not provide any relief for my OA, only pentosan did that.