This is the second excellent paper from Jim Johnson's lab:
Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan
It is slightly different from the 2012 paper as these mice are full knockout for the Ins1 gene and this time it is the Ins2 gene that is present as a full complement or at half knockout, to adjust the insulin gene dosage.
The study was never intended to compare the two diets, the diets were simply intended to provide a fairly normal insulin environment using a rodent chow against an high insulin environment generated by a Surwit type diet. It was the insulin exposure which was the focus of the study.
But, ultimately, the study did compare the two diets and in some detail.
Just to summarise the diets. Both had 4% of calories as PUFA, primarily linoleic acid. The 5LJ5 chow used a slow release carbohydrate (as uncooked ground wheat) combined with a little extra protein from soybean meal. The D12330 (Surwit type) diet was the usual hydrogenated coconut oil with maltodextrin/
Maximum individual longevities came out as expected, with the 5LJ5 coming out best and the low insulin gene dose conferring benefit to both diets.
These are the mean lifespans of the four longest lived mice in each group (top decile) as shown by the open circles/squares on the bar chart, taken from the end stage of the survival curves as shown here:
That's relatively unexciting and no one would be surprised by it.
What surprised me was the longevity advantage to the Surwit diet groups when assessed at median life span. Not only did the Surwit groups both do a great deal better than the chow groups at median lifespan but there was only a very small improvement (about 3%) obtained by reducing insulin exposure. In fact the normal gene-dose, obese, high insulin-exposure Surwit diet group (purple) had a longer median lifespan compared to the reduced insulin-exposure group that was on chow. Which was better again than that of the ordinary mice fed on chow.
If we simply ignore the reduced insulin exposure groups we can also suggest, based on these data, that the unmodified Surwit diet produces a median longevity gain in the order of 16% over a top-of-the-range excellently formulated lab animal breeding chow.
If the Surwit diet was a drug it would knock spots off of metformin, rapamycin, ethanol, caffeine or glucosamine for median lifespan extension. These mostly gain around 10% in median life span extension.
I accept that, for the four mice which made it in to extreme old age, there is a small disadvantage to the Surwit diet, but this only becomes apparent at those lifespans at over 750 days of age, out of a max of just over 900 days.
A quick look round the literature shows us that feeding a 60% fat diet where the PUFA content comes out at around 15% of total calories (high PUFA lard as the fat source), combined with Surwit-like levels of maltodextrin/sucrose, is a catastrophe. As in this one using TD.06414.
At the risk of speculating; there may be a host of problems triggered by a wheat/soybean based diet which do not appear to occur with a casein/saturated fat based diet, certainly until extreme old age is achieved. Or there could be some specific advantage to a highly saturated fat based diet which over rides the problems provided by maltodextrin/sucrose. Lots of possibilities, no obvious answers!
Fascinating study.
Peter
