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P62: A piece of the longevity puzzle
A research team deciphered the function of a protein that recognizes toxic cell proteins and disposes of them in a targeted manner. The researchers were also able to show that worms have a longer life if they produce more of this protein.
In a study, researchers at the Sanford Burnham Preby's Medical Discovery Institute showed that worms live longer if they produce a protein called p62. The results could help develop treatments for age-related diseases like Alzheimer's. Such diseases are often related to incorrectly folded proteins. The study was recently presented in the renowned journal "Nature Communications".
Improved autophagy could prolong life
According to the study, the discovered protein boosts the body's autophagy. The Japanese scientist Yoshinori Ōsumi received the Nobel Prize in Physiology or Medicine in 2016 for the discovery of autophagy. The process describes how cells break down and recycle their own components. For example, misfolded proteins that are involved in many degenerative diseases can be eliminated.
P62 has a direct impact on longevity
"Research, including our own, has shown that autophagy can improve lifespan," says Professor Dr. Malene Hansen, the lead author of the study. While it was already known that the process of autophagy is associated with aging, what is new is that the autophagy protein p62 appears to have a direct effect on longevity.
Recycling the cells
When autophagy was discovered, it was thought that cell recycling works the same for all waste products. It has now been shown that not every cell waste is recycled in the same way. The protein p62, for example, specializes in delivering labeled proteins and worn-out mitochondria (cell power plants) to the “recycling cells”.
Worms lived up to 30 percent longer
In order to better understand the role of p62 in cellular recycling and longevity, the scientists used short-lived roundworms (C. Elegans) for their studies. They genetically modified the worms so that they produced an excess of p62. As a result, the animals lived 20 to 30 percent longer. The researchers attributed the extended life to more efficient cell recycling. The p62 protein appears to be a driving force in autophagy.
Which cell waste is the most harmful?
"Now that we have confirmed that selective autophagy is important for longevity, we can move on to our next step: identifying what harmful cellular waste is being removed by p62," added Dr. Caroline Kumsta from the study team. With this knowledge, one can attack specific cell components that are associated with a shorter lifespan.
The key to curing Alzheimer's and Huntington's?
As the researchers report, many age-related and degenerative diseases, including Alzheimer's and Huntington's disease, are caused by the accumulation of toxic, misfolded proteins. An elevated p62 level could help such toxic proteins to be disposed of more effectively and thus improve lifespan and health.
It's not that easy
However, the research team warns against transferring the study results of the worms one-to-one to humans, because according to current knowledge, high p62 values in humans are associated with cancer. Nevertheless, the researchers see a lot of potential in their discovery. "In view of the known connection between p62 and cancer, it is all the more important to be able to understand the selective autophagy process from start to finish," summarizes Hansen. (vb)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Graduate editor (FH) Volker Blasek
- Caroline Kumsta, Jessica T. Chang, Reina Lee, and others: The autophagy receptor p62 / SQST-1 promotes proteostasis and longevity in C. elegans by inducing autophagy, Nature Communications, 2019, nature.com
- Sanford Burnham Preby's Medical Discovery Institute: The secret to a long life? For worms, a cellular recycling protein is key (accessed: 11.12.2019), sbpdiscovery.org