MCLK1 has been known as a mouse longevity gene for some years; reducing its activity extends life by 30% or so, apparently through the common method of reducing mitochondrial free radical generation and consequent damage. Closer inspection is producing more questions than are answered, however: "they found was that in young (3 month old) MCLK1-defective mice, mitochondria were quite energy inefficient and produced a lot of harmful oxygen radicals; yet surprisingly, when these mice were 23 months old, their mitochondria were working better than normal mice. So, despite the oxidative stress, these mice experienced less deterioration than normal. To confirm whether MCLK1-defiency could be somehow protective, the researchers crossed MCLK1-defective mice with those lacking SOD2, a major protein antioxidant. Normally, SOD2-defective mice accumulate cellular damage quickly, yet when combined with MCLK1-defiency, they exhibited less damage and oxidative stress. ... In explaining this seeming paradox, [researchers] suggest that while MCLK1-defective mice produce more oxygen radicals from their mitochondria, their overall inefficiency results in less energy and fewer oxygen radicals being produced in other parts of a cell."