Senilicidal regimes—systems that would preserve the health of the collective by eliminating elderly individuals—strike us as dystopian. But they might be just the thing for our cells. Unfortunately, some cells become old and weak and stop dividing, yet they refuse to die, despite the availability of programmed cell death mechanisms. Such cells could still be recognized and cleared away by the immune system—unless the immune system, too, is becoming feeble and increasingly dysfunctional.

To assess the degree of immune system involvement in removing senescent cells—as well as measures that could heighten the immune system’s senilicidal zeal—scientists based at the Weizmann Institute of Science worked with experimental mice that were genetically altered to incorporate specific immune deficits. After these mice accumulated senescent cells and suffered the consequences, including chronic inflammation and accelerated aging, they were given senolytic drugs, which helped eliminate senescent cells and dampen inflammation. The mice, relieved of the burden of excess senescent cells, became more active and lived longer.

It all sounds like a cellular version of Logan’s Run, a sci-fi movie that depicted a future society in which citizens self-eliminated by boarding the Carousel, a ritualistic vaporization device, when they reached 30 years of age. Reluctant 30-year-old citizens would be chased down and slain by ruthless security personnel known as the Sandmen.

In the movie, the Sandmen were, of course, the bad guys. In our bodies, however, their equivalent, the elements of the immune system, are the good guys. And sometimes, they need assistance. The forms such assistance might take could be revealed by studies like the one recently carried out by the Weizmann Institute researchers, who were led by Valery Krizhanovsky and Yossi Ovadya.

These scientists were the lead and senior authors, respectively, of an article (“Impaired immune surveillance accelerates accumulation of senescent cells and aging”) that appeared in the journal Nature Communications. The article presents findings that could shed light on the mechanisms governing senescent cells during aging. They could also motivate new strategies for regenerative medicine.

“Here we show that Prf1−/− mice with impaired cell cytotoxicity exhibit both higher senescent-cell tissue burden and chronic inflammation,” the article’s authors wrote. “They suffer from multiple age-related disorders and lower survival. Strikingly, pharmacological elimination of senescent-cells by ABT-737 partially alleviates accelerated aging phenotype in these mice.”

The scientists knocked out the gene for perforin, a pore-forming protein found in intracellular granules of effector immune cells. Encoded by the Prf1−/−gene, perforin is an important mediator of immune cytotoxicity.

Mice lacking this crucial gene had, after reaching the advanced age (for mice) of two years, had a greater accumulation of senescent cells compared with mice in which the gene was intact. The mice missing the gene suffered from chronic inflammation, and various functions in their bodies appeared to be diminished. They also looked older—and died earlier—than their normal counterparts.

“In LMNA+/G609G progeroid mice, impaired cell cytotoxicity further promotes senescent-cell accumulation and shortens lifespan,” the article continued. “ABT-737 administration during the second half of life of these progeroid mice abrogates senescence signature and increases median survival.”

In these experimental mice, as in the Prf1−/− mice, treated mice responded exceptionally well to the drug: Their blood tests and activity tests showed improvement, and their tissues appeared to be much closer to those of young mice. The scientists counted senescent cells, finding many fewer of them remaining in the treated mice’s bodies; and when they looked for signs of inflammation, they found that this, too, was significantly lower. The mice treated with the drug were more active and their median lifespan rose.

The scientists intend to continue exploring ways to prompt the human body to remove its old senescent cells, particularly to find means of activating the immune system to do this job. That is, if future experimentation proves their theories correct, they could end up creating truly “anti-aging” therapies.

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