Aubrey's "survival of the slowest" hypothesis

Aubrey de Grey ag24 at
Thu Apr 12 09:46:00 EST 2001

Iuval Clejan wrote:

> What is the reference please?

Numerous; a good place to start is anything by Muller-Hocker between
1989 and 1996.  Alternatively see Lopez et al 2000, Mutation Research
452:123, which is a particularly painstaking and thorough study.

> If in far fewer cells, it may not be important for aging.

Quite.  That's why I proposed the reductive hotspot hypothesis, Brunk
proposed the mitochondrial/lysosomal axis hypothesis and Aiken proposed
the sarcopenia hypothesis.  Brunk's model doesn't depend on mutations,
only on other mitochondrial damage; Aiken's and mine are mechanisms for
amplifying the damage.  See (e.g.) Arch Biochem Biophys 373:295, Mutat
Res 275:395 and the Lopez reference above, respectively.

> why did Dolle et al, PNAS 97 (2000)  not try to extend their experiment
> to mtDNA?

Firstly because introducing a reporter gene into mtDNA is not possible
with existing technology, and secondly because the clonal expansion
phenomenon means that the overall level of dysfunctional mtDNA is well
approximated by the frequecy of cytochrome oxidase-negative cells (see
the Muller-Hocker or Aiken papers).

Aubrey de Grey

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