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| What does research on other animals and organisms
tell us about the human aging process? |
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What have we learned from animal models of
aging about oxidative damage? |
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Our body needs oxygen to create fuel for energy. Unfortunately, the byproducts
of the chemical reactions that produce that fuel are often toxic. These
byproducts are called reactive oxygen species (some are referred to as
free radicals), and they can damage our cells' proteins and DNA. Much
research points to a central role for oxidative damage in the aging process.
Oxidative damage and its consequences have been described in all of the
animal models we have discussed. See the Oxidative
Damage Research Center for additional information about oxidative
damage.
 Yeast
Roundworms
Fruit
flies
Mice
Nonhuman
primates
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Yeast |
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Mitochondria are often called the powerhouses of cells, in that they are
tiny structures within cells that are involved in the processing of cellular
fuel. Mitochondria are also the site of much of the oxidative damage that
is believed to contribute to some aspects of the aging process. Yeast
with dysfunctional mitochondria can have extended life spans. Though some
scientists have speculated that this is due to a decrease in oxidative
damage, Dr. Michal Jazwinski at Louisiana State University has demonstrated
in his laboratory that the products of three yeast genes (RTG1, RTG2 and
RTG3) signal the yeast nucleus that the mitochondria are less than fully
functional in something called the retrograde response. Such yeast have
increased longevity. Since adding substances (such as superoxide dismutase
and catalase) to the culture media that reduce oxidative damage do not
increase the life span of the parent strains of these yeast with the defective
mitochondria, reduced oxidative damage does not appear to be the mechanism
for life span extension. Instead, the products of the RTG genes trigger
the retrograde response in the cell nucleus, which both increases life
span and delays the appearance of signs of yeast aging.
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Roundworms |
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The daf-2 gene in roundworms has been identified as important in life
span determination. A mutation in that gene can increase longevity. Mutations
in daf-2 accompanied by mutations in daf-12 enhance the roundworm's longevity,
and mutations in daf-16 reduce it. Experiments suggest that the increase
in longevity with the daf mutations is due to an increased ability to
resist oxidative damage.
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Fruit flies |
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Comparison of a long-lived strain of fruit flies (La) and a strain with
a normal life span (Ra) demonstrated that the La fruit flies were more
likely to have enhanced activity of genes that combat oxidative damage,
higher levels of protective proteins produced by those genes, and thus
an enhanced ability by those La fruit flies to resist oxidative damage.
Professors Sun and Tower of the University of Southern California have
demonstrated that fruit flies with overexpression of catalase, an enzyme
that neutralizes some of the damaging reactive oxygen species produced
in oxidative damage, are resistant to some of the deleterious effects
of hydrogen peroxide, but live no longer than other fruit flies. However,
fruit flies with overexpression of an enzyme called Cu/ZnSOD, which also
neutralizes some of the potentially damaging reactive oxygen species,
have a life span that averages 48% longer than flies without overexpression
of that enzyme.
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Mice |
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As in other animal models, oxidative damage is reduced in mice under conditions
of calorie restriction. Caloric restriction in mice has been demonstrated
to reduce the destruction of nerve cells. Thiamine deficiency is a condition
that produces nerve damage through oxidative damage. In studies from Weill
Medical College in New York, published in the journal Brain Research,
scientists demonstrated that calorie restriction could reduce the oxidative
damage caused by thiamine deficiency by half (60% of the nerve cells were
damaged in free feeding mice, versus 30% in the calorie restricted mice).
The researchers suggest that these results confirm the value of the mouse
model in understanding the relationship between aging, oxidative damage
and calorie restriction.
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Nonhuman Primates |
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Researchers at the Wisconsin Regional Primate Research Center have been
conducting studies on aging in nonhuman primates for a number of years.
They have monkeys in their study population that range up to 23 years
old, and some of them have been subjected to calorie-restricted diets
for as long as 10 years. The scientists have done skeletal muscle biopsies
on the freely fed monkeys and compared them to biopsies on calorie-restricted
monkeys. Levels of oxidative damage in skeletal muscle rose fourfold with
aging in the freely fed monkeys, but the amount of observable oxidative
damage was significantly less in the calorie-restricted monkeys.
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