Scientists studying the intricate mechanics behind the human aging process have made a discovery that could lead to improved health later in life. The breakthrough comes courtesy of a common model in anti-aging research in the form of C. elegans roundworms, with the scientists demonstrating that dialing up a form of fatty acid signaling can substantially improve their lifespan.
The research was led by Baylor College of Medicine's Dr. Meng Wang, who was inspired to study longevity and the aging process by her grandmothers, who lived to the ages of 95 and 100 and seemingly did so without significant health troubles.
“Neither was ill, and why they died remains a mystery,” she said. “It makes me feel like there’s some secret to longevity, and if we can study this, maybe we can use the knowledge and apply it to everyone.”
Wang's work over the past seven years has centered on the relationship between longevity and lysosomes, which are small sacs found in cells that are responsible for breaking down and disposing of waste products. The role that lysosomes play in age-related disease, particularly as they begin to malfunction, has come into focus among scientists seeking next-generation treatments for everything from Parkinson's, to Alzheimer's, to cancer.
“That explains why research on lysosomes and longevity has taken off in recent years,” said Dr. Xiaochen Wang, a biophysicist at the Chinese Academy of Sciences in Beijing who specializes in lysosomes. “Scientists have known for more than 50 years that proteins, lipids and other molecules tend to accumulate in cells that are old, but only now are people paying more attention to these pieces of data."
Amid all this research into lysosome function and its ties to aging, scientists have begun to uncover a separate role for these cellular recycling centers, which is to communicate messages about the state of the cell. This includes things like glucose and stress levels, but in Meng Wang has also found that this also includes specific anti-aging molecules. In 2015, her team showed that one of these molecules is released from lysosomes and sent to the cell nucleus, which had the effect of extending the lifespan of C. elegans roundworms.
These worms are a valuable tool for anti-aging researchers as they share a similar genome and many cellular pathways with humans. Studies have shown that tweaking these pathways can lead to significant extensions in the worms' lifespans, laying the foundation for the pursuit of anti-aging therapeutics in humans.
In her latest work, Wang and her team again studied the signaling coming from lysosomes, and found that a fatty acid called dihomo-gamma-linoleic acid plays an important role. As it is produced by the lysosomes, the fatty acid kickstarts a chain reaction of cellular messaging that extends the lifespan of C. elegans. Crucially, the scientists were then able to dial up the fatty acid signaling to effectively control the worms' lifespan, increasing it from an average of 17 days to between 20 to 25.
These signals that enable cells to "talk" to one another about aging demonstrates how lysosome molecules may play an influential role in coordinating aging across an entire organism, according to the team. The worm experiments showed that although the signal molecule was generated in fat tissue, it was received by cells elsewhere in the body.
“It really helps us understand how longevity is regulated at a whole organism level,” Wang said.
Wang and her colleagues will now look to build on these findings by searching for more lysosome molecules that influence the aging process, and how exactly they do so.
“The goal is not to have everyone live for centuries,” she said. “But rather for people to spend their last years healthy, active and independent – just like my grandmothers. I’m passionate to know how people and organisms sustain health with time.”
The research was published in the journal Nature Cell Biology.
Source: Baylor College of Medicine
