On calorie restriction: The last time I looked into this the data was very thin, such that finding out a major study had faked data might reduce the experimental evidence base to zero. If researchers were giving the calorie-restriction group extra food that they weren’t supposed to, it’s also likely that it was different food, which might itself explain a lifespan difference (if that food was healthier).
I think the prior is mostly against calorie restriction; looking at what the marginal energy expenditures are which would be reduced during calorie restrictions, two big ones are immunity and damage-repair, both of which are things where you’d worry about under-expenditure to produce aging-like problems. (Worse, if calorie restriction weakens immunity and this causes aging, this isn’t likely to show up in animal studies, since animals have a different set of pathogens to worry about.)
On metformin: I followed the Campbell et al to the first of the four metformin-mortality studies it cites, Bannister et. I’m not entirely sure what exactly the trick is with this study, but I’m pretty sure it’s tricky in some way. This observational study found lower mortality in type 2 diabetics with a mean A1c of 8.6% on metformin than in matched controls. Given that metformin is already the standard of care for T2DM, this would seem to imply that being diabetic reduces risk of death, rather than increasing it, which is nonsense.
I give more weight than you do to the variety of species in which calorie restriction has shown benefits.
It does seem quite possible that calorie restriction does worse in high disease environments. But humans in the developed world are exposed to a good deal less infectious disease than what we’re evolved for. That suggests that it might be healthy to weaken our immune system slightly (but there’s almost certainly an age past which that ceases to be true).
Still, I’m not at all tempted to do continuous calorie restriction. I currently do one or two days per week of limiting myself to <1000 calories, and eat until I feel full on most other days. I completely stopped calorie restriction for about three weeks near the start of the pandemic, due to increased concerns about immune system risks.
The metformin studies are downplaying some possibly important selection effects. I don’t see a need to hypothesize tricks beyond that.
Both the diabetic group and the non-diabetic group had some undiagnosed health problems. For some unknown fraction of diabetics, those health problems caused them to be excluded because doctors saw that their poor health called for a switch from metformin to a more drastic treatment. It’s unclear how a study could produce comparable selection effects in non-diabetics.
On calorie restriction: The last time I looked into this the data was very thin, such that finding out a major study had faked data might reduce the experimental evidence base to zero. If researchers were giving the calorie-restriction group extra food that they weren’t supposed to, it’s also likely that it was different food, which might itself explain a lifespan difference (if that food was healthier).
I think the prior is mostly against calorie restriction; looking at what the marginal energy expenditures are which would be reduced during calorie restrictions, two big ones are immunity and damage-repair, both of which are things where you’d worry about under-expenditure to produce aging-like problems. (Worse, if calorie restriction weakens immunity and this causes aging, this isn’t likely to show up in animal studies, since animals have a different set of pathogens to worry about.)
On metformin: I followed the Campbell et al to the first of the four metformin-mortality studies it cites, Bannister et. I’m not entirely sure what exactly the trick is with this study, but I’m pretty sure it’s tricky in some way. This observational study found lower mortality in type 2 diabetics with a mean A1c of 8.6% on metformin than in matched controls. Given that metformin is already the standard of care for T2DM, this would seem to imply that being diabetic reduces risk of death, rather than increasing it, which is nonsense.
I give more weight than you do to the variety of species in which calorie restriction has shown benefits.
It does seem quite possible that calorie restriction does worse in high disease environments. But humans in the developed world are exposed to a good deal less infectious disease than what we’re evolved for. That suggests that it might be healthy to weaken our immune system slightly (but there’s almost certainly an age past which that ceases to be true).
Still, I’m not at all tempted to do continuous calorie restriction. I currently do one or two days per week of limiting myself to <1000 calories, and eat until I feel full on most other days. I completely stopped calorie restriction for about three weeks near the start of the pandemic, due to increased concerns about immune system risks.
The metformin studies are downplaying some possibly important selection effects. I don’t see a need to hypothesize tricks beyond that.
Both the diabetic group and the non-diabetic group had some undiagnosed health problems. For some unknown fraction of diabetics, those health problems caused them to be excluded because doctors saw that their poor health called for a switch from metformin to a more drastic treatment. It’s unclear how a study could produce comparable selection effects in non-diabetics.