Autor: Julio Cesar Tafforelli | Publicado: 2014-07-10T12:50:00-07:00


    
      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




Quote:
[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




Quote:
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. 



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. elegans 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.