Mice with a defective mitochondrial protein called MCLK1 produce elevated amounts of reactive oxygen when young, which could spell disaster, but the new study found that mice actually age at a slower rate and live longer than normal mice.
Mitochondrial oxidative stress is a popular theory explaining the aging process; over time, reactive oxygen species produced by mitochondria while they make energy slowly accumulate and begin damaging cells, including the mitochondria.
During the study, Siegfried Hekimi and colleagues examined the mitochondria of MCLK1-defective mice, a strain known for its longevity, at various ages.
They found that in young (3 month old) MCLK1-defective mice, mitochondria were quite energy inefficient and produced a lot of harmful oxygen radicals, but 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 further understand if MCLK1-deficiency 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-deficiency, they exhibited less damage and oxidative stress.
The 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.
Thus while these mice may have some higher risks of damage when young, they accumulate less damage as they age, a finding that seems to indicate the mitochondrial stress theory may not be correct.
The study appears in Journal of Biological Chemistry.