X-Message-Number: 27695
Date: Fri, 10 Mar 2006 10:04:02 -0800 (PST)
From: Doug Skrecky <>
Subject: mechanical, not free-radical damage may drive fly aging

[The failure of mitochondria-targeted coenzyme Q10 (or mitoquinone) to
retard aging, pretty much eliminates the free radical theory of aging, as
least with regards to drosophila. This leaves what I call mechanical
damage theories of aging. These can be defined as metabolism related,
accumulating damage not driven primarily by free radicals. A human example
of this sort of damage is "mechanical" telomere erosion during cell
division. Another example would be accumulation of cell membrane-derived
dolichol inside cells. (However free radicals can actually RETARD
this accumulation.)
  Below, drosophila flying, which is a metabolicly intensive activity,
was found to be associated with accelerated aging. There is a saying
"Use it or Lose it", which may apply to mammals, because of their
ability to replenish damaged cells. However exercise is not beneficial to
flies, which lack this ability. Note also, that reduced temperature can
dramatically increase fly lifespan, and that this intervention also
greatly reduces physical activity.
  A possible counter to this flying-aging link, is derived from my own
fly longevity experiments. In run #22, very high doses of either
blueberry or prune juices greatly reduced fly movement, but actually
slightly reduced longevity. Lower doses in run #97, had no effect on
either movement, or on longevity. However it is likely that very high
doses of these juices *increased* the generation of free radicals, to the
point, where these could begin to negatively affect lifespan.]

 Mech Ageing Dev. 2006 Apr;127(4):356-70. Epub 2006 Jan 25.
The effects of exogenous antioxidants on lifespan and oxidative stress
resistance in Drosophila melanogaster.
  We used the fruit fly Drosophila melanogaster to test the effects of
feeding the superoxide dismutase (SOD) mimetic drugs Euk-8 and -134 and
the mitochondria-targeted mitoquinone (MitoQ) on lifespan and oxidative
stress resistance of wild type and SOD-deficient flies. Our results
reaffirm the findings by other workers that exogenous antioxidant can
rescue pathology associated with compromised defences to oxidative
stress, but fail to extend the lifespan of normal, wild type animals. All
three drugs showed a dose-dependent increase in toxicity in wild type
flies, an effect that was exacerbated in the presence of the redox-cycling
drug paraquat. However, important findings from this study were that in
SOD-deficient flies, where the antioxidant drugs increased lifespan, the
effects were sex-specific and, for either sex, the effects were also
variable depending on (1) the stage of development from which the drugs
were given, and (2) the magnitude of the dose. These findings place
significant constraints on the role of oxidative stress in normal ageing.

J Gerontol A Biol Sci Med Sci. 2006 Feb;61(2):136-45.
Flight activity, mortality rates, and lipoxidative damage in Drosophila.
  In this study, the effect of flight activity on mortality rates and
lipoxidative damage in Drosophila was determined to identify mechanisms
through which oxidative damage affects life span. The results showed that
flies allowed flying throughout life had higher mortality rates and
decreased median and maximum life spans compared to controls. The
mortality rate of the flight activity group could be lowered, but not
completely reversed by switching to control conditions; and the accrued
oxidative damage could not be eliminated. The levels of reactive oxygen
species produced by mitochondria isolated from high activity and control
flies did not differ significantly. However, the high activity flies had
altered membrane fatty acid compositions, which made them prone to
increased lipid peroxidation. The effect of flight activity on insect
life span differs considerably from the beneficial effects of exercise in
mammals; these differences may be caused by physiological differences
between the two taxa.

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