Nature doi:10.1038/nature13012

Credit: NATURE

The progressive accumulation of free radicals in the mitochondria due to DNA damage and long-term cellular metabolism has been associated with aging, but the ability to accurately monitor these correlations has been challenging. Recently, a cpYFP reporter (called Mitoflash) was developed to detect random bursts of superoxide production in the mitochondrial matrix, reflecting changes in oxidative stress and metabolism. Shen et al. applied Mitoflash in a model organism of aging, the nematode Caenorhabditis elegans, to determine whether changes in Mitoflash frequency could predict lifespan. They detected two major peaks of Mitoflash activity: an early peak (day 3) and a late peak (day 9), when worms begin to die. The authors examined genetic mutants and worms exposed to short- or long-term environmental or pharmacological conditions and surprisingly found a strong negative correlation between the frequency of the early peak and overall worm lifespan. Long-lived worms exhibited lower day-3 Mitoflash frequencies compared to wild-type worms, whereas short-lived worms showed higher frequencies. The authors sought to explain the connection of Mitoflash and lifespan by examining the regulation of mitochondrial metabolic pathways. In particular, upregulation of the glyoxylate cycle in a long-lived mutant promoted metabolic flux through complex II, resulting in decreased superoxide production and Mitoflash activity. The authors caution that the day-3 Mitoflash activity is a marker, not a causal factor of aging. This study suggests that aging is a programmed process in which the mitochondrion organelle has a central role.