"On June 8th, 2003, the inaugural Methuselah Prize was awarded to Dr. Andrzej Bartke for the "Methuselah Mouse" that lived the equivalent of 180 human years".
You can read a bit more about growth hormone receptor knockout mice and other forms of dwarf mice in Dr Bartke's review, written soon after winning the prize:
Life extension in the dwarf mouse.
It's now 2018 and no one appears to have improved on the Laron mouse model which won that initial prize. Over the last 15 years there has been a lot of interesting research but no numerical progress. I think it is worth noting that Laron mice are not GH deficient, they have tons of the stuff. They simply do not have the receptor to do anything with it. Which, in particular, means they cannot generate IGF-1.
How do Laron humans fare? The best studied group live in Colombia. They're of very short stature. They have no recorded cases of diabetes and only one recorded cancer, which was non lethal*. Their every biochemical parameter is exemplary, especially insulin level and HOMA score. Do they all live to be centenarians? Apparently not. Being a dwarf in Columbia requires alcohol in large amounts to render life tolerable, plus accidental trauma is another huge problem. Quite what would happen if these people lived under similar conditions to the Laron mice in Dr Bartke's laboratory is a question which is unlikely ever to be answered! Longevity in the real world vs what works under ideal conditions...
*Dr Laron has reported two cases of Laron Syndrome people developing diabetes (and there are others), including the complications such as atherosclerosis, renal disease and diabetic retinopathy. This is an interesting observation and might be worth a post on its own some time.
There are tantalising suggestions from other GH modifying mutations in humans. One of the better studied of these is carried by the "Little people" of Krk in Croatia. More from Dr Laron:
Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?
Longevity of the hypopituitary patients from the island Krk: a follow-up study
They have a mutation which causes multiple pituitary hormone deficits, ACTH secretion excepted. There are too few documented people with this genetic problem to say a great deal about longevity but ages of 68, 77, 83 and 91 years have been recorded in the four individuals to have died since detailed observations began. The equivalent syndrome in mice under lab conditions promotes longevity.
One of the nicer studies looking at human height (viewing this as a GH/IGF-1 signalling surrogate) and longevity is this one:
Shorter Men Live Longer: Association of Height with Longevity and FOXO3 Genotype in American Men of Japanese Ancestry
It found, as you might expect, an inverse relationship between height at enrolment and longevity. They also tied the relationship, observationally, to a down-regulating SNP of the FOXO3 gene, FOXO genes being major controllers of the insulin/IGF-1 signalling system.
Which genes you have is not under your control. What you do with then might well be...
Let's finish this post with the LoBAG diet. It's modest (20% of calories) in carbohydrate, has 30% of calories from protein and the rest as fat. It's being compared to a diet with similar carbohydrate content, 15% of calories from protein, with the rest as fat. Lots of details in here:
The metabolic response to a high-protein, low-carbohydrate diet in men with type 2 diabetes mellitus
As they say in the discussion:
"The present data indicate that the increase in IGF-1 is the result of the increase in protein content. The further decrease in carbohydrate did not result in a further increase in IGF-1. In fact, the increase was approximately the same (138% and 136%, respectively)".
What interested me initially (and had made me chase the paper) was the effect on GH itself. The LoBAG diet actually drops GH levels, admittedly by a ns amount. What turns out to be a much more interesting incidental finding is that, despite the downward trend in GH, IGF-1 rises by a statistically significantly and possibly by a biologically significant amount. Especially when you consider a whole slew of cancers sprout IGF-1 receptors on their surface.
Brief aside. You have to be very careful with GH and IGF-1 levels in papers like this one as both hormones come with a whole load of plasma binding proteins which very few people, including the LoBAG folks, ever measure. These may well alter the effective concentration of the hormone either upwards or downwards. Caution is needed with simple measurements like those in this paper. End aside.
So. Folks should eat whatever they feel comfortable with, protein-wise. I probably eat a little more protein than I would prefer, but then I'm no perfectionist. What I wouldn't do is to add protein gratuitously to any meal...
But that's just me I guess.
Peter
