Cancer researchers here stumble upon a way to alter mitochondrial function to improve health and extend life in mice. A range of the known ways to slow aging through genetic alteration work through similar mechanisms to those shown here, creating somewhat dysfunctional mitochondria that can still perform their necessary functions but which generate a raised level of damaging oxidative molecules in the process. This spurs cells to increase cellular housekeeping activities in response, which in turn leads to a net gain in cellular health and function. Over the lifespan of an organism these small differences in every cell add up.
The mice, which lack the TRAP-1 protein, demonstrated less age-related tissue degeneration, obesity, and spontaneous tumor formation when compared with normal mice. TRAP-1 is a member of the heat shock protein 90 (HSP90) family, which are "chaperone" proteins that guide the physical formation of other proteins and serve a regulatory function within mitochondria.
The researchers found that in their knockout mice, the loss of TRAP-1 causes mitochondrial proteins to misfold, which then triggers a compensatory response that causes cells to consume more oxygen and metabolize more sugar. This causes mitochondria in knockout mice to produce deregulated levels of ATP, the chemical used as an energy source to power all the everyday molecular reactions that allow a cell to function.
This increased mitochondrial activity actually creates a moderate boost in oxidative stress ("free radical damage") and the associated DNA damage. While DNA damage may seem counterproductive to longevity and good health, the low level of DNA damage actually reduces cell proliferation - slowing growth down to allow the cell's natural repair mechanisms to take effect. "Our findings strengthen the case for targeting HSP90 in tumor cells, but they also open up a fascinating array of questions that may have implications for metabolism and longevity. I predict that the TRAP-1 knockout mouse will be a valuable tool for answering these questions."