You might recall that mice engineered not to express the protein p66Shc live 30% longer, but it's not entirely settled as to why this is the case. The protein p66Shc is required for some methods of programmed cell death in response to damage and failing function, so removing it lowers the rate at which cells destroy themselves in response to stresses:
Free radicals (a category that includes reactive oxygen species) lead to oxidative stress, a term for damage caused to cellular mechanisms by these chemicals. Cells destroy themselves via apoptosis in response to excess oxidative stress, a process initiated in the mitochondria, so as to prevent their own failing mechanisms causing further damage to the body - but the processes of identifying just when is most advantageous to do so are quite varied and complex. The protein p66Shc [is] an important part of one scheme by which a cell starts in on destroying itself.
p66Shc knockout mice exhibit higher catalase activity [and] removing p66Shc extends life - but is this because of a lowered rate of apoptosis with oxidative stress, or is it in fact the higher levels of catalase, an antioxidant that helps soak up the free radicals before they break things? As I'm sure regular readers recall, engineering mice to have more catalase in their mitochondria is good for a 20-30% boost in life span.
There's more on the mechanisms of p66Shc over at ScienceDaily today:
Activated by cellular stress, four p66Shc molecules form a stabile complex via Cystein-Cystein interactions. Only this complex can introduce the controlled cell death by causing the mitochondria to burst. The p66Shc activity can be arrested by the Glutathione and Thioredoxin cellular protective systems, which are capable of breaking down stress damages, substances that cause stress and the activated p66Shc complex. "p66Shc acts in this capacity as a stress sensor", explains Dr. Steegborn.
"The cell's suicide program is apparently only started when these protective systems can no longer handle the cellular stress, and are subsequently also no long capable of deactivating p66Shc that has already been activated."
Mice in which the gene for p66Shc, which is closely related to the human equivalent, has been removed do in fact live some 30% longer than normal mice, but the suspicion is that this gain in lifespan is achieved at the expense of correct function; i.e., that the organism is more susceptible to malfunctions due to cell damage.
Which is interesting, but my money is still on the catalase theory.