CR and rate of maturation

Aubrey de Grey ag24 at
Thu Oct 1 11:30:25 EST 1998

In continuation of this thread:

ADG>The mice used for typical CR
ADG>experiments have been bred in captivity for many generations, and may
ADG>therefore have been quite heavily selected for rapid maturation.

BR > Stop right there! Walford, Weindruch, Spindler and everyone else who
BR > does CR experiments use special, long-lived hybrid mice for CR
BR > experiments. These mice are unusually resistant to the diseases of
BR > aging and live a long, long time for mice.

ADG>Yes, but I'm not sure that that completely rebuts the challenge, since
ADG>these mice may still have been quite substantially selected for fast
ADG>maturation and short lifespan, just less so than typical lab strains.
ADG>Do these mice live close to the maximum lifespan potential of wild Mus
ADG>musculus?  How accurately is the MLSP of wild Mus musculus known?

(which I summarise since it lost some groups mid-way), Brian Rowley wrote:

> I don't know what the lifespan of wild Mus musculus is. However, it's
> the sort of thing Alex Comfort has published in his books on aging.
> It seems most unlikely that wild Mus musculus would have a longer
> maximal lifespan than Walford's long-lived hybrids. There are fierce
> selective pressures in the wild for early reproduction. Rapid
> senescence almost invariably goes along with early reproduction (Jay
> Olshansky and Robin Holliday are references). Since the rate of
> attrition is high in the wild, there is little evolutionary pressure
> for longevity. Therefore I see no reason why wild Mus musculus would
> live as long as Walford's carefully selected, longevous hybrids.

I'm not at all sure about that.  The link between rate of maturation and
rate of aging is indeed very clear -- that's where my question began --
but the pressure for early reproduction in the lab is also fierce, very
fierce.  I can see no clear argument that it is less fierce than that in
the wild; if it is fiercer, the difference may not have been outweighed
by Walford's selection.  I'll explore more, and would be grateful for
pointers from those who know this literature well (eg Brian D or Steve).

This question is made rather more interesting by the finding you noted
that McCay got a bigger life extension than is found with the longevous
hybrids.  McCay's work of course predated the development of the modern
and sophisticated protocols for avoiding artifacts.  Have *all* recent
studies used the longevous hybrids?  If not, and if modern studies with
typical lab strains also get bigger life-extension than those with the
longevous hybrids, then it becomes positively parsimonious (rather than
just plausible) to speculate that lifespan of *species* (as opposed to
strains) with very long lifespan may be less increased by CR than that
of those with short lifespan, despite the many biochemical similarities.
This is why I think it may be very valuable to find reasonably accurate
data on this, and why I'd be surprised if it's not readily to hand.

Aubrey de Grey

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