Image Credit: HoPo (Wikimedia) ©️CC BY-SA 3.0
Scientists are faced with a new paradox: A small adjustment at the cellular level can significantly extend lifespan. But this extended life does not come with a more resistant body, but on the contrary, with a more sensitive structure.
Scientists from McGill University in Canada have revealed that triggering a low level of stress response (scientifically known as mitoUPR) in mitochondria, the energy production centers of cells, extends lifespan in nematode worms called Caenorhabditis elegans, which are used as a model organism.1
The key point of the research is this: This life extension does not occur by increasing the ability to cope with stress, but on the contrary, by decreasing this ability.
What Happens If Mitochondria Go On Alarm?
Mitochondria within the cell play a vital role in protein production and energy metabolism. When these organelles are stressed, a kind of alarm system is activated. It’s called mitoUPR. This system activates the cell’s genetic defenses to recover.
In this study, scientists developed a type of worm in which the gene called ATFS-1, the main actor of the mitoUPR system, was constantly active. Normally, this gene is activated when the cell is under stress, but this time it was kept constantly active.
The result?
These worms are more resistant to external stress factors. But interestingly, they have a shorter lifespan.
So what happened next?
Scientists gradually reduced the activity of this gene with RNA interference (RNAi). In other words, the gene was not completely silenced, but its effect was reduced. Thanks to this intervention, a balance point was reached where the ATFS-1 gene was low but constantly active.
In this case, the worms’ lifespan was significantly extended compared to the control group.
But be careful! This longevity did not come with stress resistance. In other words, the worms lived longer, but they were much more easily affected by external threats such as oxidative stress, temperature changes, and lack of oxygen.
The results obtained directly challenge a biological assumption that has been valid for a long time. In fact, longevity is generally attributed to the ability to cope with stress. In this study, the exact opposite was revealed.
The researchers also examined at what age this genetic intervention was effective. The intervention did not only work in adulthood, but when it was done during the developmental period, which we can call childhood, there was a significant increase in lifespan.
This also shows that the long-term life plan is determined by cellular adjustments made at a young age. Interventions made after adulthood do not work very well.
So What Does This Study Tell People?
Model organisms such as Caenorhabditis elegans play a major role in understanding genetic mechanisms due to their simple structures. And a significant portion of these mechanisms are shared with humans. Therefore, inferences on topics such as mitochondrial function, stress responses, and the relationship between aging can shed light on human biology.
However, it should be stated clearly: It is not correct to say that these results are directly applicable to humans. No study conducted on humans has yet shown that this level of molecular intervention extends life.
- Di Pede Alexa, Ko Bokang, AlOkda Abdelrahman, Tamez González Aura A., Zhu Shusen and Van Raamsdonk Jeremy M. 2025Mild activation of the mitochondrial unfolded protein response increases lifespan without increasing resistance to stressOpen Biol.15240358 http://doi.org/10.1098/rsob.240358[↩]
