R. Cutler found that animals with the highest levels of SOD are the longest lived. Humans have the highest levels of mammals, and they are the longest lived. Chimpanzees have half our level of SOD, and they live half as long as us. Tortoises have the highest levels of SOD and are the longest living animals.
The life span of fruit flies decreases 80% when the gene for cytosolic SOD is knocked out, and increased 40% when SOD is over-expressed. Drosophila, incidentally, has no mitochondrial gene for glutathione peroxidase. Knockout of the the mtDNA gene for mitochondrial SOD in mice causes early death. On the other hand, the knockoutof cytosolic SOD does not much impact mouse life span.
Extra-Cellular SOD can exist on external cell surfaces and in the extra-cellular matrix, being expressed highly in the lungs to protect against hyperoxia. Structurally, it contains a heparin-binding domain sensitive to proteolysis differentiating it from cytosolic SOD or mitochondrial SOD. When EC-SOD was applied to cells in culture, telomeres shortened only 5-20 bp per population doubling, as opposed to 50-100 bp under standard conditions. from "Telomeric Damage in Aging" by Thomas von Zglinicki, in Aging at the Molecular Level, ed. T.Zglinicki, pp 124-125. .