The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

History of the Mitochondrial Free Radical Theory of Aging, 1954-1995
macromolecular degradation which determine lifespan are not the same as in warm-blooded
animals (see Section 10.5).
Nonetheless, it is undeniable that comparing and contrasting the details of a process in
multiple different species is a hugely useful approach in biology. Its role is very similar to
that of mutational analysis, where the ultimate effects of a genetic alteration—that is, a
comparison of a mutant organism with a wild-type one—can be used to demonstrate, for
example, that the product of gene X stimulates or inhibits the expression of gene Y.
Comparisons between vertebrate (and very long-lived invertebrate) species have been used
extensively, especially in recent years, in an attempt to gain insight into what controls the
rate of aging. Several relationships have emerged as being of particular importance, and
they will be discussed in turn here.
6.5.1. Longevity and Specific Metabolic Rate
An extremely obvious inter-species correlation with regard to longevity is that bigger
animals tend to live longer. Unfortunately this is not (on the face of it) a very valuable
insight, since not only does it fail to suggest any mechanisms, but also it is a necessary
consequence of the fact that growth—cell division, in particular—entails a complex and
intricate series of chemical reactions, and therefore takes time. If an animal is capable of
reproduction when it is only a few millimetres long, it can tolerate living only a few days; if
it cannot reproduce until it is a few metres long, it needs to live a lot longer.
One can, however, make more progress if one examines the relationship of these two
variables with a third: body temperature. This differs very greatly between warm-blooded
animals (homeotherms) and cold-blooded animals (poikilotherms). All homeotherms
maintain about the same body temperature, and doing so obviously requires the conversion
of nutrients into heat, which consumes oxygen. An animal’s oxygen consumption (which is
easy to measure, unlike, for example, its heat output) is thus a measure of the rate at which
it is then using nutrients—its metabolic rate. An animal’s metabolic rate varies—it increases
when the animal is physically active, and decreases during sleep—so it is usual to measure
standard metabolic rate, which is defined to be that when the animal is awake but at rest.
From that one establishes the animal’s specific metabolic rate by dividing its standard
metabolic rate by its mass. This is the interesting number, because it is a measure of how
hard the average cell is having to work to keep the animal warm. Since smaller animals have
a higher ratio of surface area to volume, and hence of surface area to body mass, they end up
needing a higher specific metabolic rate in order to maintain the same body temperature.*
So the question is: is there a correlation between specific metabolic rate and longevity?
Do animals of similar sizes but different specific metabolic rates have different longevity?
Indeed they do. A poikilotherm of a given size generally lives much longer than a homeotherm
of the same size. 25 Unlike the early observation that lifespan varies with size, this need not
necessarily be so. Furthermore, the same relationship applies to poikilotherms kept at different
temperatures: fruit flies live only about half as long at a given temperature as at 10˚ C cooler
(within their range of good viability, of course). 26 This is also a measure of specific metabolic
rate, since for poikilotherms specific metabolic rate varies with temperature just like any
chemical reaction.
* Intriguingly, the relationship between mass and specific metabolic rate that is seen is not precisely the
obvious one. One would naturally predict that the rates of animals whose body temperatures were the same
would vary as the inverse 2/3 power of their mass, since our surface is two-dimensional and our bodies are
three-dimensional. In fact it is almost exactly the inverse 3/4 power. 24 This may not sound like much of a
difference, but it has kept eminent comparative biologists in business for many years.
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