Surprising results from a recent study show that stressing a cell can reverse signs of cellular aging. The findings might open doors to more successful ways to slow the aging process.
Although the desire to stave off aging has a whiff of vanity about it, it’s not all about reducing wrinkles and covering gray hair; getting older comes with a range of diseases that grow steadily more prevalent as our population ages.
Those interested in senescence are keen to understand the molecular pathways involved in aging in the hope that associated disease processes will also be unlocked.
Molecular bioscientists from Northwestern University in Evanston, IL, recently gained a new and surprising insight into cellular aging. Their findings are published this week in the journal Cell Reports.
This new study focused on the transparent nematode Caenorhabditis elegans. This species is often used as a model for human aging and disease; its cellular properties and biochemical environment are similar to our own.
Despite the fact that life in the wild rarely allows an organism to survive into old age, all animals age when given the chance. Events and processes that happen as an animal ages are shared across species.
For instance, as C. elegans ages, the way that it handles proteins in the cell, or proteostasis, is compromised. For a cell to function properly, proteins must be built, folded, and degraded at the correct rates. The machinery responsible for this becomes progressively less accurate as time goes on, resulting in misshapen and faulty proteins building up in the cytoplasm.
Similarly, in humans, misfolded proteins accumulate as part of some neurodegenerative conditions, such as Huntington’s, Parkinson’s, and Alzheimer’s disease.
The researchers behind the new study, which was headed up by senior study author Prof. Richard I. Morimoto, put the cells’ mitochondria — or the so-called powerhouses of the cell — under mild duress.
What they found came as a surprise: under these conditions, mitochondria sent out signals to the protein machinery, preventing it from failing. This, in turn, reduced the buildup of badly packed proteins.
These surprising findings fly in the face of the previously held notion that stressing mitochondria has negative effects, as Prof. Morimoto explains. He says, “This has not been seen before.”
“People have always known that prolonged mitochondrial stress can be deleterious,” he explains. “But we discovered that when you stress mitochondria just a little, the mitochondrial stress signal is actually interpreted by the cell and animal as a survival strategy. It makes the animals completely stress-resistant and doubles their lifespan. It’s like magic.”
These unexpected findings offer a new and intriguing lens with which to view the aging process in humans; they may provide a key to how the process might be slowed.
“Our goal is not trying to find ways to make people live longer but rather to increase health at the cellular and molecular levels so that a person’s span of good health matches their lifespan.”
Prof. Richard I. Morimoto
The new study’s findings are based on earlier work carried out by Prof. Morimoto and Johnathan Labbadia, a former postdoctoral fellow in Prof. Morimoto’s laboratory who now works at University College London in the United Kingdom.
In a previous study, they found that in C. elegans, deficits in proteostasis begin at reproductive maturity. The decline is sparked by inhibitory signals from the germline cells that prevent tissues from producing protective responses to stress. In C. elegans, this occurs 8–12 hours after the onset of adulthood, but the animal will normally live for another 3 weeks.
Knowing when C. elegans would begin the decline, in the current study, they used 2-day-old animals. They hoped to be able to identify the genes and pathways involved that produce the molecular failure.
Prof. Morimoto and his team screened approximately 22,000 genes on the hunt for those responsible for the decline. They honed in on a set of genes called the mitochondrial electron transport chain (ETC), which seemed to be important. “Mild downregulation of ETC activity” resulted in healthier animals, as did small doses of xenobiotics and exposure to pathogens.
As Prof. Morimoto explains, “I never would have guessed this — a low stress signal resets the organismal lifespan profoundly. What we are learning is that some of these stress signals are interpreted by the organism as a way to reset itself and to live longer. When mitochondria function optimally, the cells and tissue are robust.”
Designing a way to implement these findings in a form that will be useful for humans is a long way off. However, the study sheds new and unexpected light on the still mysterious process of aging. Simply adding new avenues to follow is a result in itself.