The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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The Mitochondrial Free Radical Theory of Aging
however, essentially impossible to distinguish between extremely slow senescence and
non-senescence. Perhaps the strongest evidence that these species really do not senesce comes
from their maintenance of fecundity, 29,30 since it has long been a central tenet of evolutionary
theory that reproductive senescence tends to precede other aspects of aging; however, this
has yet to be tested in a representative variety of species.
If mtDNA decline is indeed so important in aging as is claimed here, then we can infer
that any vertebrate which essentially avoids senescence must also avoid mtDNA decline. A
technically straightforward experiment, therefore, is to measure the levels of any class of
mtDNA lesion (either deletions or point mutations) in animals of a given negligibly senescing
species spanning a wide range of ages.
Similarly, downstream effects of oxidative stress are just as straightforward to measure
in negligibly senescing species as in others. Accumulation of lipofuscin, of oxidatively
damaged proteins and of cross-linking in collagen have all been the subject of preliminary
studies, 30,31 but much more extensive analysis is clearly required before we can form a detailed
picture.
A third aspect of negligibly senescing species which is strongly predicted, though not
absolutely required, by MiFRA is that they should have virtually no cell types which become
unrenewable in adulthood. This does not mean they have no cells which are postmitotic—that
would indeed be remarkable, since, for example, the syncytial character of muscle fibres is
a fundamental consequence of their construction, and syncytial cells are constitutionally
unable to undergo further mitosis. But, unless the cells continue to grow indefinitely without
division—something that should be readily detectable in dissected muscle as increased
length and/or cross-sectional area of fibres—it does mean that all postmitotic cells must
be associated with precursor cells which can proliferate to replace them as and when they
die, and also that such replacement actually occurs (as opposed to the situation in
mammalian muscle, for example, where it occurs in response to larger-scale cell death
such as a wound or toxin-induced necrosis 32 but does not maintain fibre number during
aging). 33 Biogenesis of muscle fibres and nerves throughout life has indeed been reported
in amphibians (though not specifically in negligibly senescing species), 34 but such work
clearly needs to be conducted on a larger scale.
References
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