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[Posted on behalf of CRON4healthyfuture; 2006-03-08]

Hey, IGF-1/Insulin skeptics: More evidence you are as stupid as you sound

A little blurb from the Salk Institute..........ever heard of it? Oh, wait, I forgot, it's not a theoretical paper, so it's worthless, right?

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http://www.newswise.com/articles/view/518594/

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"Together with the lab of another Salk scientist, Tony Hunter, Ph.D., Dillin’s team identified a protein in the worm Caenorhabditis elegans that allowed them to do just that. The protein is encoded by the Smk-1 gene. “Smk-1 is the first known gene that regulates longevity without affecting other vital functions of the insulin signaling pathway,” said Wolff.
Under favorable conditions, a still unidentified molecule binds to DAF-2, the worms’ equivalent of the insulin/IGF-1 receptor, which is located at the cell’s surface. A cascade of signaling molecules relays the information deep into the cell till it reaches a protein called DAF-16. Known as a transcription factor, DAF-16 encodes a DNA-binding protein that turns on other genes but when DAF-2 is active, it is unable to enter the cell’s nucleus to activate its target genes.
When environmental conditions turn harsh as a result of overcrowding and scarce nutrients, for example, DAF-2 signaling shuts down. No longer marooned outside the nucleus, DAF-16 crosses into the nucleus, and triggers all the necessary genes to help the body take care of the stressful situation. But food shortages aren’t the only triggers for the stress program. Others are the heat that scrambles proteins into toxic clumps and marauding parasites. Highly reactive molecules known as free radicals also unleash DAF-16.
If the worms are having a good day in a favorable environment, but for some reason DAF-2 signaling gets turned off precociously, the worms reap the benefit of increased stress resistance and double their lifespan from an average of 20 to 40 days. Except the worms trade a trim life focused on reproduction for a long life with fewer progeny and a tendency to halt larval development and enter a dormant, hibernation-like stage in which they can hang on for months but don’t reproduce.
Unless Smk-1 is missing, that is.
Without Smk-1 to provide guiding assistance, DAF-16 is unable to slow down the aging process, and the worms die young. “These mutants are shorter lived because they are unable to respond appropriately to oxidative stress, but they are just as resistant to heat stress as wild type worms whose signaling pathways have not been experimentally manipulated,” explained Wolff.
“In the future, we may use this protein as a tool to study the genetic and metabolic requirements for extending longevity without causing diverse, wide-ranging effects on the development and maintenance of the physiological equilibrium in the organism,” said Dillin.
Researchers, who contributed to this paper include graduate student Denise Burch and postdoctoral researchers Gustavo A. Maciel in Dillin’s laboratory and Hui Ma in Hunter’s laboratory.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes."