Because lysosomes are the dumping site for cellular waste products, researchers have begun to study them in greater detail, suspecting a connection to aging. Within the past decade, scientists have shown that lysosomes serve as a platform the cell uses to send messages about its general state, such as its glucose and stress levels. In 2015, Meng Wang was one of the first to discover specific anti-aging signals produced by lysosomes in the roundworm C. elegans.The CAS’s Wang says the work stands out because it was conducted in a living organism, rather than in the cultured cells researchers typically use to study lysosomes. Additionally, those experiments showed how one particular molecule released from lysosomes traveled to the cell’s nucleus and acted as a signal that extended the worm’s lifespan. “It’s a very beautiful piece of work,” she says.

From one cell to another

The newly published study in Nature Cell Biology takes the research one step further. In work led by Wang’s PhD student Marzia Savini, the Baylor team discovered that when lysosomes produce a fatty acid called dihomo-gamma-linoleic acid, it triggers a chain reaction of cellular messages that ultimately extend the worms’ lives. When the researchers dialed up this fatty acid signaling, worms lived 20 to 25 days, an increase from the normal lifespan of 17 days. Crucially, the signal molecule was generated in fat tissues, yet detected by neurons elsewhere in the worms. That means lysosomes produce signals that cells use to coordinate longevity across different tissues.

“Our previous work showed that lysosomes send signals within the same cell, but this work shows that they can talk to other cells too,” explains Wang. “It really helps us understand how longevity is regulated at a whole organism level.”

Today, Wang and her team continue to hunt for other molecules lysosomes produce that may act as anti-aging signals. There’s still so much to uncover, she says, such as figuring out when the molecules begin acting as signals, how they regulate aging, and how that function withers with age. In August, Wang will move her lab to HHMI Janelia Research Campus in Ashburn, Virginia, where she will be a senior group leader.

The goal isn’t to have everyone live for centuries, says Wang, but rather for people to spend their last years healthy, active, and independent – just like her grandmothers. “I’m passionate to know how people and organisms sustain health with time.”

Citation

Marzia Savini et al. “Lysosome lipid signaling from the periphery to neurons regulates longevity.” Posted on bioRxiv.org on June 10, 2021. doi: 10.1101/2021.06.10.447794. Published in Nature Cell Biology on June 9, 2022. doi: 10.1038/s41556-022-00926-8