New insights into cell longevity could boost research in age-related diseases

Some insulin-producing cells in the pancreas live as long as neurons do, Salk Institute scientists discovered. (Wikimedia Commons)

It’s a well-known fact in the scientific world that neurons can survive for as long as we live. But what about the other cells of the body?

A team of researchers at the Salk Institute set out to find the answer to that question, in the hopes of gaining insights that might improve the search for new cures for diabetes, heart disease and other age-related disorders. What they found surprised them.

The team examined tissues from the brains, livers and pancreases of mice and discovered very old cells—some of which had lifespans rivaling those of neurons. They published their findings in the journal Cell Metabolism.

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“Our goal was to visualize the age of cells in different tissues,” said lead author Rafael Arrojo e Drigo, Ph.D., a staff scientist at Salk, in a video interview (see below). The researchers started with neurons and then examined cells from the liver and pancreas.

The team used advanced imaging and electron isotope labeling to quantify turnover among cells and proteins in the organs they studied. The Salk researchers worked with scientists at the University of California, San Diego, to develop new microscopy methods so they could properly pinpoint the age of each cell they imaged, according to a statement. Once they established a baseline from neurons in the brain, they compared their findings to the other cell types.

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The liver can regenerate fresh tissue, so the Salk team was surprised to find that the majority of cells there were as old as neurons. They also discovered some long-lived cells lining blood vessels—another unexpected finding.

The pancreas is largely a mystery because it contains several cell types with an unknown capacity for longevity. But the researchers found old cells there, too. “Our study now suggests that most cells in the liver and in the pancreas are as old as the brain,” Arrojo e Drigo said.

This mix of old and new cells, which the Salk team referred to as “age mosaicism,” could shed light on how cells maintain and repair themselves throughout adulthood. That could spark ideas for new ways to prevent or treat diseases like diabetes, the researchers said.

For example, the Salk team discovered that some insulin-producing beta cells in the pancreas continued to replicate, constantly producing young cells, while others did not divide but lived as long as neurons. They hope to learn in future studies how these differences contribute to type 2 diabetes.

When the researchers selected a variety of long-lived cells to study further, they found proteins within them that also displayed age mosaicism. Some neurons and beta cells from the pancreas had both very young and very old proteins, while the liver cells had no long-lived proteins.

The next step for the Salk team is to probe the lifespans of nucleic acids and lipids. Their ultimate goal is to quantify the total effect of age mosaicism on not just diabetes, but also cardiovascular disease and dementia.

“We’d like to understand how those very long-lived cells age, what kind of molecular changes drive them sometimes into pathological states,” said Hartin Hetzer, Ph.D., chief scientific officer of the Salk Institute in the video. “By discovering and understanding those mechanisms and those processes, we also hope to either delay or maybe even prevent some of the age-related changes that we observe in different tissues.”

 

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