The mice that live longer under CR are the ones that can preserve their weight/fat after all!
Did you see a paper that supports this weekend idea? Please post
I have looked into PPARgamma and it’s very confusing. In general PPARgamma agonists like Pioglitazone are potentially beneficial for longevity because they generally imrove insulin sensitivity and inflammation. PPARgamma activation increases weight gain, which normally would be harmful, but they tend to do this by increasing subcutaneous fat while decreasing visceral fat, with the overall effect resulting in improved insulin sensitivity, hence why they are used for diabetes.
At the same time, there is also a common polymorphism which is a missense mutation in the PPARgamma2 gene referred to as pro12ala PPARgamma polymorphism. It is found in roughly 10% of the population (I happen to have it). That polymorphism is associated with reduced activity of PPARgamma. Yet it has been associated with improved insulin sensitivity. Also while increased PPARgamma may benefit insulin sensitivity, it might actually accelerate aging of the thymus (thymic involution involves a lot of thymic cells being converted into fat cells and PPARgamma activation might accelerate this). Thiazolidinedione treatment and constitutive-PPARgamma activation induces ectopic adipogenesis and promotes age-related thymic involution - PubMed
I also found very conflicting evidence on whether the pro12ala polymorphism has beneficial or negative effects on lifespan in humans.
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