A candle that burns twice as bright and twice as long: the PEPCK-Cmus transgenic mouse
April 28 2008 / by mycophage / In association with Future Blogger.net
Category: Health & Medicine Year: 2008 Rating: 9 Hot
(Cross-posted from Ouroboros: Research in the biology of aging.)
A transgenic mouse that lives twice as long as controls is also
stronger and faster, arguing against the idea of inherent negative
tradeoffs associated with lifespan extension. 
Increased expression of a metabolic enzyme, phosphoenolpyruvate carboxykinase (PEPCK, an enzyme that most of us learned about in freshman biology and then promptly forgot, reasoning that the descriptive name and the ability to look it up if necessary would suffice if it ever came up again) results in mice that are muscular, have lower body fat than a runway model, and able to run 25 times farther than a wildtype control.
Even more interesting, according to proud parents Hanson and Hakimi, the females of the PEPCK-Cmus strain mate and have normal-sized litters at 35 months, an age when the blood of wildtype mice has cooled substantially (and, indeed, the mice themselves are starting to check out). The implication is that aging is slowed, and longevity extended, as a result of the transgene.
It’s become reflexive to ask whether a long-lived mutant is living longer because it’s calorie-restricted for some reason, incidental to the main phenotype conferred by the mutation, but this is not the case here: In order to preserve their enviable bods, PEPCK-Cmus mice eat 60% more than controls — so they’re not extending their lifespan by dieting. If anything, they’re anti-dieting: their increased metabolic efficiency means they’re harvesting more calories per gram of carb or fat than normal animals. No word yet on what happens if you do try to calorie-restrict them; I can imagine it going either way but am holding out hope for tiny explosions. (cont.)
there are a bunch of folks whose stomachs are growling as we speak that will be disappointed to learn that this strategy may be flawed.