September 20, 2005
From the desk of Jane Galt:Boy, he shure do talk purty
This sounds really interesting. I just wish I understood more than every third word:
Some of the most interesting anti-aging genes that have turned up in roundworms and flies have to do with insulin (and insulin-related growth factor, IGF) signaling. This team of researchers thought that the Klotho protein might fall into the same category, and they were right: the protein seems to lower insulin sensitivity by affecting signaling through the insulin and IGF receptors.Here’s where my drug-discovery radar started pinging. These receptors are part of a family that carries their own kinase along to phosphorylate themselves, and that’s a key even in their signaling cascade. This new work noted that Klotho suppressed autophosphorylation of the receptors, and that makes sense, considering the downstream effects. It’s very interesting to note that compounds that affect the IGF receptor kinase are already being developed. They’re potential anticancer agents, and a number of companies seem to be working on them.
Klotho is a gene which, when doubled, extends mouse lifetimes by 30 percent or more. The protein this gene codes for affects the way insulin signals the cells to do something; the receptors that insulin affects have their own little action enzyme (kin- as in "kinetic" and "-ase" for an enzyme; a kinase is an enzyme that makes something happen) that causes them to bind with phosphorus. (I'd guess from ATP, the source of energy thourghout the body, but I don't know.)
The way that the Klotho protein does this, according to this new research, is by keeping this reaction from happening, which means the cell isn't signalled to do what it does with the insulin. (In fat cells, it's to bind fats; in other cells, its to metabolize glucose. When your cells don't react to insulin, your blood sugar goes up, which is what type II diabetes is. Type I is when an autoimmune disease kills the cells that make the insulin instead.)
"Here's where my drug discovery radar starts pinging." He's noting that there are a number of drugs already known that do something similar. As he said in the article, since artificially induced type II diabetes hasn't been a big market, people haven't looked at them much, but IF one of these drugs had the same sort of effect as the Klotho protein, THEN it would be an effective anti-aging drug. And since these drugs are already through part of the drug discovery and testing process (since there're being looked at for anti-cancer properties too) the process of getting them into actual testing for anti-aging properties would be much quicker too.
Interestingly, it sounds like the Klotho protein might be a specific for obesity too.
If lowering insulin sensitivity makes you live longer does that mean it's healthy to be really fat?
There must be a catch somewhere...
No, it works the other way --- insulin tells the body to store fat. If you block the insulin, you reduce the ability to store fat.
So my having type II diabetes is a good thing? Somehow I don't think my doctor would agree.
Type II diabetes is insulin insensitivity.Fat cells secrete a substance(TNF alpha) that makes insulin bind less well.Certain meds (Actos, Avandia),certain natural substances(cinnamon,Mg) also restore insulin sensitivity.However there is nothing in the blurb above to suggest these meds/substances can increase above the baseline in normalpeople.(Although I think a clinical trial is using Actos as stroke prevention.)
There is data decades old on simple organisms (flatworms)fed extremely low calorie diets having far prolonged lifespans.Interestingly,their first generation descendants have somewhat extended spans.This has lead some rspected researchers to sugest a very low calorie diet as a way to slow aging-independent of CVA effects.
There area variety of things that can be done to extend (or more accurately optimize)life :
baby aspirin/day-slightly less if female
statins-alsohave very strong anti cancer effects
regular exercise
grape juice-boosts good cholesterol
picking your parents well.
Scifi greats Heinlein(see Lazarus Long),Niven(Louis Wu)and Andersen(The Boat of a Million Years)have written great stories of people with extended lives.
And of course The Chronicles of Amber (Zelazny)
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