Now, Dillin and his team have expanded that finding by discovering new details about how mitochondria in the brain communicate with cells across the worm’s body to extend life.
First, he had to understand why damage to the brain’s mitochondria could possibly have a beneficial effect on the organism. A mitochondrion’s process for generating energy requires exceedingly complex molecular machinery with dozens of different protein parts. When things go awry, such as when some components are missing or misfolded, mitochondria activate a stress response, known as the unfolded protein response, which delivers repair enzymes to help the complexes assemble properly and restore mitochondrial function. In this way, the unfolded protein response keeps cells healthy.
Dillin expected this process to unfold only inside the neurons with damaged mitochondria. Yet he observed that cells in other tissues of the worm’s body also turned on repair responses even though their mitochondria were intact.
It’s this repair activity that helped the worms live longer. Like taking a car to a mechanic regularly, the unfolded protein response seemed to keep cells in good running order and function as anti-aging detailing. What remained mysterious was how this unfolded protein response was communicated to the rest of the organism.
After some investigation, Dillin’s team discovered that the mitochondria in stressed neurons were using vesicles — bubblelike containers that move materials around the cell or between cells — to carry a signal called Wnt beyond the nerve cells to other cells in the body. Biologists already knew that Wnt plays a role in setting up the body pattern during early embryonic development, during which it also triggers repair processes like the unfolded protein response. Still, how could Wnt signaling, when turned on in an adult, avoid activating the embryonic program?
Dillin suspected that there had to be another signal that Wnt interacted with. After further work, the researchers discovered that a gene expressed in the mitochondria of the germline — and in no other mitochondria — can interrupt Wnt’s developmental processes. That result suggested to him that germline cells play critical roles in relaying the Wnt signal between the nervous system and tissues throughout the rest of the body.
“The germline is absolutely essential for this,” Dillin said. It isn’t clear, however, whether the germline mitochondria act as amplifiers, receiving the signal from the brain’s mitochondria and transmitting it to other tissues, or if the receiving tissues are “listening” for signals from both sources.
Either way, the strength of the germline signal regulates the organism’s life span, Dillin said. As a worm ages, the quality of its eggs or sperm declines — what we refer to as the ticking of a biological clock. The decline is also reflected in the germ cells’ changing ability to transmit signals from the brain’s mitochondria, he suggested. As the worm grows older, its germline transmits the repair signal less effectively, and so its body declines, too.
Scientists don’t yet know whether these findings apply to humans and how we age. Still, the hypothesis makes sense from a broader evolutionary standpoint, Dillin said. As long as the germ cells are healthy, they send pro-survival signals to ensure that their host organism survives to reproduce. But as the quality of the germ cells declines, there is no evolutionary reason to keep extending life span further; from evolution’s perspective, life exists to reproduce itself.
The fact that mitochondria can talk among themselves might seem somewhat alarming, but there is an explanation. Long ago, mitochondria were free-living bacteria that joined forces with another type of primitive cell to work together in what became our modern complex cells. So, their ability to communicate is probably a relic from the free-living bacterial ancestor of mitochondria.
“This little thing that’s been ticking inside of cells for billions of years still retains its bacterial origins,” Dillin said. And if his research in worms holds up in more complex organisms like humans, it’s possible that your mitochondria are talking right now about your age.
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Larisa Mongold