A lifespan extension of 60 percent has been achieved in worms by disrupting a mechanism in mitochondria using simple antibiotics
Why is it that within a homogeneous population of the same species, some individuals live three times as long as others? This question has stumped scientists for centuries.
Now, EPFL researchers led by Johan Auwerx report in the journal Nature how a mechanism in mice plays a determining role in longevity. And they go a step further: by disrupting this mechanism using simple antibiotics in a population of nematodes, or roundworms, they can multiply lifespan by a factor of 1.6.
Mitochondia: biological timekeepers
The process identified by EPFL scientists takes place within organelles called mitochondria, known as the cellular powerhouses because they transform nutrients into proteins including adenosine triphosphate (ATP), used by muscles as energy.
But that’s not all they do. Several studies have shown that mitochondria are also involved in aging. The new EPFL research, done in collaboration with partners in the Netherlands and the US, pinpoints the exact genes involved and measures the consequences to longevity when the amount of protein they encode for is varied: less protein, longer life.
Natural variations in mice
Laboratory mice in the BXD reference population typically live from 365 to 900 days. This population, which reflects genetic variations that occur naturally within a species, is used by many researchers in an approach known as “real-world genetics.” The benefit of working with this population in particular is that their genome is almost completely decoded.
The team led by professor Auwerx, head of EPFL’s Laboratory of Integrative and Systemic Physiology, analyzed mice genomes as a function of longevity and found a group of three genes situated on chromosome number two that, up to this point, had not been suspected of playing any role in aging. But the numbers didn’t lie: a 50 percent reduction in the expression of these genes—and therefore a reduction in the proteins they code for—increased mouse life span by about 250 days.
Extending life in worms
Next, the team reproduced the protein variations in a species of nematode, Caenorhabidtis elegans. “By reducing the production of these proteins during the worms’ growth phase, we significantly increased their longevity,” says Auwerx.
The average life span of a worm manipulated in this way went from 19 to more than 30 days, an increase of 60 percent. The scientists then conducted tests to isolate the common property and determined that the presence of mitochondrial ribosomal proteins (MRPs) is inversely proportional to longevity.
The researchers concluded that a lack of MRP at certain key moments in development created a specific stress reaction known as an “unfolded protein response” within the mitochondria. “The strength of this response was found to be directly proportional to the life span,” says Auwerx. “However, we noted that it was more pronounced if the protein imbalance—the reduction in MRP— occurred at a young age. A similar stimulation in an adult did not affect the worms’ longevity.”
What’s more, the effect can be induced without genetically manipulating the worms. “Exposure to certain readily available drugs inhibits ribosomal function and thus causes the desired reaction,” says Auwerx. In other words, mitochondria are sensitive to certain antibiotics, and the drugs can be used to prolong life.
via Ecole Polytechnique Fédérale de Lausanne & EurekAlert
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