A New Treatment Restored Youth to Decrepit Mice by Killing "Zombie" Cells

If we want to extend life, we might need to lean into death.

The point of an anti-aging pill — the holy grail of anti-aging — would be to help avoid death, or at least put it off for as long as possible. For researchers who are exploring anti-aging therapies, prolonging the life of cells has been a prime strategy. But a new paper released in Nature Communications indicates that if we want to extend life, it might be worth leaning into death. If we sacrifice a few aging cells at the altar of eternal youth, the team’s experiments found, it could pay off later on.

Previously, scientists have turned to research on telomere lengthening or multi-drug cocktails to help slow the march of aging in our cells. But some researchers, including Valery Krizhanovsky, Ph.D., a molecular biologist at Israel’s Weizmann Institute of Science, have a slightly different approach. For years Krizhanovsky has played with the idea that aging is linked to the accumulation of cells in our bodies that aren’t quite dead yet but are still clinging to life. His earlier research indicated that we might be able to target these “zombie cells” and kill them. In the most recent paper, he showed that when he killed these cells off in mice, it extended their lives and made them strangely youthful.

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Krizhanovsky's research focuses on removing decrepit cells to help slow the process of aging 

At a certain point, some cells in the body reach an age when they stop dividing. Typically these cells are supposed to die on their own, but some cells — called senescent cells — stubbornly live on. Krizhanovsky explains that these senescent cells do have some useful functions at first, but problems arise when they stick around too long and accumulate in certain tissues.

“We believe that senescent cells contribute to conditions of chronic inflammation and that’s why they contribute to aging,” Krizhanovsky tells Inverse. “They’re fine when they’re formed but we don’t want them to stick around for a long time.”

His recent paper explains that by helping our immune system remove these cells, we can partially reverse their harmful effects. He showed this in a series of experiments on mice by messing with a genetic “on-switch” that helped their immune systems target these aging cells — this actually hampered their ability to detect these decrepit cells, which promoted premature aging. Then he looked to reverse the process by giving them a drug, called ABT-737, which he hoped would arm the immune system with the capacity to find the aging cells and destroy them.

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The mice treated with ABT-737 had far fewer senescent cells (blue)  in their bodies than controls and lived slightly longer.

Compared to controls, the mice who were treated with ABT-737 lived 24 days longer — which doesn’t seem like much but was statistically significant by the team’s calculations. More importantly, they noticed some weirdly youthful behaviors in the geriatric mice. The ABT-737 group was twice as active as the control group at the end of the first month of treatment.

Helping rid the body of these senescent cells is actually the point of a whole category of anti-aging related drugs, called senolytics, of which many are currently in development. Krizhanovsky adds that his paper shows the key role that the immune system plays in this process.

But while this result seems promising, he notes that we still don’t know what may happen over time when we help the immune systems target aging cells for removal. Krizhanovsky’s experiment was conducted over several months, but there could be unforeseen (and perhaps disastrous) consequences in the long term. Right now, he’s working on identifying what those risks might be.

Krizhanovsky sees this experiment as a proof of his concept, and hopefully, a pathway to a new senolytic drug down the line.

“When we remove senescent cells, and we’ve shown this, we reduce the level of inflammation in the organism and in tissues. That’s what contributes to extension of survival,” he says. “Now we know it is the immune system that keeps senescent cells in check.”