April 28 2008 / by mycophage
Category: Health & Medicine Year: 2008 Month: Apr 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.)
The PEPCK-Cmus seem to have
it all: great bodies, long lives, extended reproductive and sexual
lifespans, and no need to limit their appetites. The down side?
Apparently, they are complete as*holes: the mutants are aggressive
and hyperactive, traits heretofore unheard-of among
muscular, fit humans (and, indeed, in the field of
biogerontology).
Rigorous lifespan and aging studies in these animals are
ongoing, but are not yet complete, so the authors are reserving
final judgment on the question of whether PEPCK-Cmus transgenics are bona fide
longevity mutants. Hopefully we’ll have an answer within a couple
of years. In the meantime, I hope they’re busily cross-breeding the
transgene into short-lived DNA repair
mutants — recently shown to
induce longevity-assurance pathways in a last-ditch effort to
stave off progeria — both to accelerate the progress of research
and to see whether the metabolic benefits of PEPCK-Cmus might be used to treat
premature aging syndromes.
(Hat tip to
Longevity Meme.)
(Cross-posted from
Ouroboros: Research in the biology of aging.)
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