Visual Measurement of Mitochondrial Free Radicals Predicts Longevity in Nematodes
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Researchers have engineered a clever system to visually determine levels of free radical activity in the mitochondria of nematode worms, something that can be automated to a fairly high degree, which in turn enables the collection of much more data, leading hopefully to more rigorous conclusions. The same approach could be employed in other species, such as mice, though it would take much longer and require more manual effort - such as regular tissue sampling in a population of mice - to run the same experiments to correlate levels of mitochondrial free radical production to life span.

Mitochondria are important in the aging process because they are central to many vital cellular processes, but suffer damage to their DNA - the blueprints for their component proteins - as the result of free radicals emitted in their normal operation. Or perhaps it isn't due to free radical damage but more a matter of mistakes occurring during DNA replication: mitochondrial DNA doesn't benefit from the same level of quality control and repair machinery as does the DNA in the cell nucleus. Regardless of whether free radical levels are causing harm in this way, they are also important to the operation of metabolism through other channels. Different longevity-inducing mutations have been noted to either raise and lower the normal levels of free radical generation in various species. So on the one hand it is argued that hormetic effects cause a boost in repair mechanisms throughout the cell, producing a net benefit despite more free radicals running around, while on the other hand its also argued that reducing levels of free radicals leads to less damage in the first place and thus much the same net benefit.

Equally, any or all of these longevity mutations could be extending life through other mechanisms that have less to do with free radicals: there is a lot of room yet for theorizing even though the mainstream consensus heavily favors oxidative damage as an important mechanism. Understanding the operations of the cell is a complex business for individual cells, never mind a whole body full of them.

The importance of this present research quoted below is as a reference system, one that can be ported to other species to generate better hard data on what exactly is going on with regard to free radical levels across a life span. That will make it much easier in the years ahead to pin down cause and effect in a variety of mechanisms related to mitochondria - I can immediately think of half a dozen things I'd like to see tested in conjunction with a form of this technology ported to mice.

Lifespan predicted from flashes in worm cells

[Researchers] added proteins to nematode worms that fluoresce when they detect damaging free radical molecules in their mitochondria. Mitochondria generate a cell's energy. It's long been thought that an accumulation of free radicals, produced when cells metabolise, drives the ageing process by damaging DNA and proteins. Mitochondria are particularly at risk because they produce free radicals in large quantities but lack the DNA repair mechanisms found in other parts of the cell.

[The] team found that the number of "mitoflashes", caused by the presence of free radicals, emitted when a nematode was three days old could predict its lifespan. Worms typically live for 21 days and are at their peak of reproductive fitness at 3 days old. Those with low mitoflash activity at that time lived longer, while those with high mitoflash activity died before day 21.

Worms carrying a genetic mutation known to extend life to 39 days exhibited fewer mitoflash bursts than genetically healthy worms, and free radical production peaked later in their lifespan. Conversely, worms with a life-shortening mutation exhibited much higher than average mitoflash frequency which peaked earlier.

The same pattern was seen when the team exposed the worms to short periods of starvation and heat shock, environmental stresses that counter-intuitively increase lifespan, and to a toxic herbicide known to shorten lifespan.

Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans

It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level.

Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals.

Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C.‚ÄČelegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.

Comments

I wonder what would happen to the worms' lifespans if Matthew O'Connor and his team at the SENS mountain view research center allotopically expressed and imported the mitochondrial genes in a nematode worm?

Posted by: Jim at February 12, 2014 8:23 PM

After reading this I wondered, how long they might live after being treated with a C60 Olive Oil preperation, as it is speculated that the C60oo is taken up by the mitochondrial membrane, where it acts as a free-radical sponge.
If the speculation is correct there should be a significant change in the mitoflash frequency and lifespan of the worms.

Posted by: Mike at February 12, 2014 11:37 PM

C60 in olive oil doesn't work, you have to dissolve the C60 in pure snake oil...

Posted by: Jim at February 15, 2014 1:17 AM
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