The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 17 No. 6 • July 2014


FLASH! MITOCHONDRIAL THEORY OF AGING SUPPORTED IN NEW STUDY

Production of Superoxide Bursts by Mitochondria Can Be Detected as Flashes

Rate of Flashes in Early Adulthood Predicts Lifespan in C. elegans

In 2008, researchers published a paper demonstrating that “mitochondria in mammalian cells undergo quantal, stochastic bursts of superoxide production, which can be visualized as ‘mitochondrial flashes’ (mitoflashes) by the sensor protein circularly permuted yellow fluorescent protein (cpYFP) in the mitochondrial matrix.”1

As the researchers explain in their introduction to their 2014 paper on mitoflashes, Dr. Denham Harman conceptualized the mitochondrial theory of aging (MTA) in 1972.2 They go on to say: “The mitoflash frequency is highly sensitive to oxidative stress and metabolic changes; it can therefore be exploited as a readout of energy metabolism and free radical production for testing MTA.”3

Using this ingenious method, the researchers now report that there was a highly significant “negative correlation between the day 3 mitoflash frequency and lifespan” that held true for strains of C. elegans with a normal, faster, or slower aging rate. “… worms with low mitoflash activity as a group lived significantly longer than those with medium or high mitoflash activity.”3

Furthermore, the researchers explain, “In long-lived daf-2 animals [C. elegans with a mutated daf-2 gene], decreased mitochondrial production of superoxide through a shift in metabolic flux from Complex I to Complex II contributes to a slowing of organismal aging.” “These data strongly support a coupling between the mitochondrial function and the process of ageing … .” Indeed, the researchers report in this study that the variation of day 3 mitoflash frequency alone explained 59% of the variation in lifespan using a nonlinear cubic spline regression model or 50% using a simple linear regression model. The scientists even tested their model in C. elegans exposed to 26 conditions that have been found experimentally to alter lifespan, finding that the strong negative correlation between day 3 mitoflash frequency and lifespan held, with the 3 day mitoflash frequency alone explaining 52% of the lifespan variation with the linear regression model or 70% using the cubic spline regression model.

The researchers conclude: “This finding provides the most direct evidence for a central role of mitochondria in lifespan regulation.”

Our thanks to Dr. Denham Harman for his early recognition of the importance of mitochondria in aging. We thank the researchers who did this mitoflash study for citing Dr. Harman’s 1972 publication on the subject;1 being ahead of your time can often mean, in science, that your early work isn’t always cited and later elaborations on the subject by others often get the recognition.

References

  1. Wang et al. Superoxide flashes in single mitochondria. Cell. 134:279-90 (2008).
  2. Harman. The biologic clock: the mitochondria? J Am Geriatr Soc. 20:145-147 (1972).
  3. Shen, Song, Lin, et al. Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans. Nature. 508:128-32 (2014).

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