Senescent Cells: The Reason Why We Age

Saturday - November 11 2023, 04:07 UTC - 1 year ago

Senescent cells are biochemical waste factories that leak into their local environment, increasing inflammation and damaging healthy cells. A new study suggests that an FDA-approved drug may inhibit the process, and when given to mice, had better kidney, liver, and lung function within two months. Senescent cells employ a 'factory' within the cell to package and ship their toxic payload, with high levels of SASP proteins releasing hormones that can further damage the body.

Senescent cells are biochemical waste factories.A new study suggests that a way to wipe them out is a medicine already approved for eye problems.Dubbed "zombie cells," senescent cells slowly accumulate with age or with cancer treatments. The cells lose their ability to perform normal functions. Instead, they leak a toxic chemical soup into their local environment, increasing inflammation and damaging healthy cells. Over a decade of research has shown eliminating these cells with genetic engineering or drugs can slow down aging symptoms in mice. It's no wonder investors have poured billions of dollars into these "senolytic" drugs.

There are already hints of early successes. In one early clinical trial, cleaning out zombie cells with a combination of drugs in humans with age-related lung problems was found to be safe. Another study helped middle-aged and older people maintain blood pressure while running up stairs. But battling senescent cells isn’t just about improving athletic abilities. Many more clinical trials are in the works, including strengthening bone integrity and combating Alzheimer’s.

But to Carlos Anerillas, Myriam Gorospe, and their team at the National Institutes of Health (NIH) in Baltimore, therapies have yet to hit zombie cells where it really hurts. In a study in Nature Aging, the team pinpointed a weakness in these cells: They constantly release toxic chemicals, like a leaky nose during a cold. Called SASP, for senescence-associated secretory phenotype, this stew of inflammatory molecules contributes to aging.

Lucky for us, this constant release of chemicals comes at a price. Zombie cells use a "factory" inside the cell to package and ship their toxic payload to neighboring cells and nearby tissues. All cells have these factories. But the ones in zombie cells go into overdrive.

The new study nailed down a protein pair that’s essential to the zombie cells’ toxic spew and found an FDA-approved drug that inhibits the process. When given to 22-month-old mice—roughly the human equivalent of 70 years old—they had better kidney, liver, and lung function within just two months of treatment.

The work "stands out," said Yahyah Aman, an editor at Nature Aging. It’s an "exciting target for new senolytic drug development," added Ming Xu at UConn Health, who wasn’t involved in the study.

A Molecular Metropolitan .

Each cell is a bustling city with multiple neighborhoods. Some house our genetic archives. Others translate those DNA codes into proteins. There are also acid-filled dumpsters and molecular recycling bins to keep each cell clear of waste.

Then there’s the ER. No, not the emergency room, but a fluffy croissant-like structure. Called the endoplasmic reticulum, it’s Grand Central for new proteins. The ER packages proteins and delivers them to internal structures, the cell’s surface, or destinations outside the cell.

These "secretory" packages are powerful regulators that control local cellular functions. Normally, the ER helps cells coordinate their responses with neighboring tissues—say, allowing blood to clot after a scrape or stimulating immune responses to heal the damage.

Sene Cells’ Toxic Factory .

But as researchers learn more about senescent cells, it’s become clear that this part of the cell has gone haywire. Constant secreting of SASP proteins harms the local area around the cells, creating chronic inflammation. While these proteins normally heal us after tissue damage, high levels release hormones like cortisol and serotonin, called "alarmins," that can further damage our body.