Note that these mice were fed a high fat diet (HFD), essentially toxic fat overload to generate disease phenotypes that one can demonstrate an improvement in. M

Note that these mice were fed a high fat diet (HFD), essentially toxic fat overload to generate disease phenotypes that one can demonstrate an improvement in. Mice normally eat a mainly grain based diet, so getting 45% of calories from fat is as you can imagine pretty bad for them. This is a common theme in anti-ageing research. When you administer some cariacature of poor lifestyle, it is much easier to find ways to improve things. The long running calorie restriction experiements in monkeys illustrate this well [1,2] - in monkeys being fed a bad diet, calorie restriction works great. In monkeys eating a kinda normal monkey diet, calorie restriction doesn't do much (and the unrestricted healthy eating monkeys live longer than the calorie restricted junky monkeys). Peter Attia had a good podcast with Steve Austad where they discuss this, albeit paywalled. Unfortunately the style of experiment in the OP is good for publishing papers but hardly advances knowledge or helps us to explain anything. It is much more difficult to demonstrate improvements in healthspan in animals that are living well. The ITP experiments have shown a few drugs can do this, with rapamycin being the most broadly effective. [1] Junky monkey: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812811/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812811/ [2] Healthy monkey: https://www.nature.com/articles/nature11432 https://www.nature.com/articles/nature11432