Protein Regulates Insulin to Extend Lifespan

The protein, called Klotho, is found in various species. In mice, it performs like a hormone circulating through the bloodstream and attaches to cells.

Treatments based on this hormone may provide a means to extend the life span of living organisms or lessen the effects of aging, according to Dr. Makoto Kuro-o, assistant professor of pathology at the University of Texas Southwestern Medical Center (Dallas, TX, USA) and senior author of the study, which was published in the August 25, 2005, online edition of the journal Science. "It could be one of the significant steps for developing anti-aging therapy,” noted Dr. Kuro-o.

Dr. Kuro-o and coworkers initially discovered the Klotho gene in 1997, naming it after one of the mythical Greek fates who controlled the length of human life. Their earlier studies demonstrated that mutant mice lacking the Klotho gene appear healthy until approximately three to four weeks old, when they begin to show signs of aging, developing osteoporosis, skin atrophy, arteriosclerosis, and emphysema. The mice died prematurely at about two months.

For the current study, the investigators created a second strain of mutant mice in which the Klotho gene produced more of the protein than in normal mice. Those mice lived between 19-31% longer than normal mice. The scientists were particularly interested in how the hormone affected insulin, because making an animal resistant to insulin increases its lifespan--a phenomenon found in animals ranging from worms to mice.

The mice with higher levels of Klotho had more insulin in their system than the healthy mice, indicating that the Klotho mice were resistant to insulin; they had to generate it to make up for the resistance. The contrary was true with the mice lacking Klotho. They were more sensitive to insulin and had decreased levels of it.

The influence on insulin creates an obstacle for Klotho should it be used as an anti-aging therapy. It may lengthen life spans, but it could also make an animal diabetic. Mice with the excessive Klotho also had less offspring than normal mice, according to Dr. Kuro-o.




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University of Texas Southwestern Medical Center