Simultaneous overexpression of Cu, Zn SOD, and CAT in Drosophila was shown to increase the maximum and average lifespan by one-third, to retard the age-related accumulation of oxidative damage to DNA and protein, to increase resistance to the oxidative effects of X-ray exposure, to attenuate the age-related increase in the rate of mitochondrial H2O2 generation, to increase the speed of walking, and to increase the metabolic potential defined as the total amount of oxygen consumed during the adult life per unit body weight (Orr and Sohal, 1994). Moreover, others have been able to extend the Drosophila lifespan by overexpressing either Mn-SOD or Cu,Zn-SOD in motor neurons. Very recently, it became possible to modestly increase longevity in mice by overexpressing mitochondrially targeted catalase (Schriner et al., 2005). However, Schriner's report is somewhat vulnerable to technical criticisms on the grounds of the experimentally observed mosaic expression of the transgene and nonphysiological targeting of the enzyme (mitochondria in transgenic vs. peroxisomes in WT animals). In Drosophila, overexpression of Cu,Zn-SOD or CAT alone failed to extend lifespan (Orr et al., 2003). Additionally, overexpression of Cu,Zn-SOD failed to increase longevity in mice (Gallagher et al., 2000).
VARIATIONS IN LONGEVITY AMONG DIFFERENT SPECIES CORRELATE INVERSELY WITH THE RATES OF MITOCHONDRIAL GENERATION OF SUPEROXIDE ANION RADICAL (O2'") AND H2O2
As has been mentioned earlier, a longer lived subpopulation of Drosophila was found to have a lower rate of mitochondrial O2*_ and H2O2 generation (Sohal et al., 1986). Similar results were observed in a recent cross-species study of bats, shrews, and mice, where mitochondria from long-lived bats were found to produce half to one-third the amount of hydrogen peroxide per unit of oxygen consumed compared to mitochondria from shrews and mice, respectively (Brunet-Rossinni, 2004).
RESTRICTION OF CALORIC INTAKE LOWERS STEADY-STATE LEVELS OF OXIDATIVE STRESS AND DAMAGE, RETARDS AGE-ASSOCIATED CHANGES, AND EXTENDS THE MAXIMUM LIFE-SPAN IN MAMMALS
Reducing dietary intake has been shown to be the most effective means for modulating the aging processes in laboratory rodents (Weindruch et al., 1986). Dietary restriction also has been shown to be a modulator of membrane lipid peroxidation and cytosolic antioxidant status. Lee et al. studied the anti-ROS action of dietary restriction by quantifying the formation of the O2* OH", and H2O2 by liver microsomes from rats of various ages. The results show that the ad libitum-fed group maintained a higher production of O2*_ and OH" radicals when compared to the food-restricted group of the same age. H2O2 formation followed the same trend but was statistically greater only at three and six months of age. The food-restricted group displayed higher SOD activity in both cytosolic and mitochondrial fractions compared to ad libitum-fed controls (Lee and Yu, 1990). These data indicate that the ROS activity observed in liver micro-somes of ad libitum-fed rats can be attenuated by dietary restriction, thereby providing a possible mechanism for its life-extending action.
Was this article helpful?