Over 15 years of research on correlations between superoxide dismutase
(SOD) activity and aging or life span have failed to provide a consis
tent picture of the role of SOD in aging. While genetic manipulations
that increase CuZn-SOD activity have only a slight, if any, effect on
maximum life span in several species, they do increase resistance to o
xidative stress. However, increasing both CuZn-SOD and catalase does s
ignificantly increase maximum life span. Decreased SOD expression in a
variety of species increases their vulnerability to oxidative stress,
and in the case of genetically altered CuZn-SOD, leads to premature d
eath of motor neurons in humans. Little is known about the regulation
of expression of SOD and other antioxidant defense enzymes in eukaryot
es. The research summarized below collectively suggest that SOD plays
an important role in longevity and degenerative disease, but much rema
ins to be learned before manipulation of SOD expression can be conside
red for effective intervention in either process.