• What are “senescent” cells?
• Chemo experiments with mice
• Amazing effects of clearing scenescence
• Future research
• References

The side effects of chemotherapy are the stuff of nightmares. Excruciating pain of every kind, frequent nausea, utter exhaustion, dizziness, heart damage, and depression. It’s a severe test of one’s resolve that can last for months after treatment. But what if there were a drug that could make these vanish, or at least ease them, substantially? What a godsend that would be.

Well, recent research strongly suggests that such a drug could be on the way.

Add “senescent cells” to your vocabulary

As we age, our cells naturally divide less and less frequently—and then divide no more, entering a state called senescence. Studies suggest that 50 is the maximum number of divisions in an average lifetime. It’s not yet clear why there’s a limit, but what’s important is that these senescent cells are by no means just lying around doing nothing.

Once they reach their senescent state, they keep busy releasing an unhealthy array of proteins and various compounds known to cause inflammation. And, as we know, inflammation is the likely point of origin for almost every disease we study. And, as we age, and our immune systems weaken, and the number our of senescent cells increases, so does the incidence of inflammation becoming chronic. A veritable welcome mat for multiple diseases.

So senescent cells can not only do some very serious damage to surrounding tissue. They’re also thought to be responsible, in part, for those horrific side effects of chemotherapy. And that’s not all. We’re seeing evidence that strongly links senescent cells to a growing list of age-related diseases, including:

• Muscle wasting
• Cataracts and glaucoma
• Alzheimer’s and Parkinson’s
• Osteoporosis and arthritis
• Heart failure and high blood pressure
• Cancers
• Lung, liver, kidney and skin disorders

Mice with an unhealthy glow

For a closer look, a research team in the Netherlands genetically engineered a strain of mice so their senescent cells would light up, or fluoresce. They then gave the mice cancer, and gave them one of four common chemotherapy drugs: doxorubicin, cisplatin, paclitaxel or temoz.

Results?

The chemotherapy increased the number of senescent cells in the mice. In places where they weren’t really expected.

“We saw senescence everywhere: in the liver, lung, heart, skin and fat,” says team leader, Marco Demaria. The mice also started showing typical chemo side effects, becoming less active and developing problems with their hearts and bone marrow, for instance.

In another experiment, a week after they had received chemotherapy, mice were given a drug that kills senescent cells. Guess what? Their side effects were alleviated. The mice shrugged off their fatigue, became more active, and didn’t develop any of the health problems common in the other mice. “We are able to interfere with multiple side effects at the same time,” says Demaria.

And better still, these mice were also less likely to have their cancer return later on—a problem that’s been plaguing powerful cancer therapies since forever. Imagine what a relief it would be to hear “Your cancer is in remission—for keeps.”

The team next analyzed blood cells from women with breast cancer. Bingo again. Women with higher blood levels of senescent cells before chemo had more severe side effects during and after chemo.

It’s pretty clear by now that purging senescent cells might help guard against unpleasant side effects among chemo patients.

But it gets better.

A silver bullet?

Here’s where research and evidence team up to present the possibility of new treatments. In this instance, a new treatment that’s beginning to look like a silver bullet, that one researcher says “…would revolutionise the way medicine is practised.”

Wow. Clear-eyed, cautious, methodical research experts don’t often make such sweeping statements.

So here’s why Judith Campisi, at the Buck Institute for Research on Aging in California, is so excited.

Super-mice? Super-people next?

Old mice that were cleared of senescent cells became like-new “super-mice.”

“Treated mice,” Campisi says, “were stronger in old age, and looked younger, with plumper, less wrinkled skin.”

Take a deep breath and ponder that for a moment.

Being stronger, looking younger, being free of typical age-related disease, and for some, free of chemo side effects—aren’t these the dreams of almost every person of advanced age?

Are we homing in on a single, omnipotent intervention that could make chemo less horrible while attacking and eliminating many, even all, age-related diseases?

“That’s the dream,” says Ms. Campisi. ”Instead of seeing separate specialists for heart disorders, cancer and dementia, a single doctor would take a more holistic, preventive approach to your health.”

Should that come to pass, we’re indeed looking at “revolutionary” change.

A work in progress

Such promise. But one cell type does not fit all just yet. While the research you’ve just read about tempts us to roll out the nearest senescent cell killer, it’s not, of course, that simple. Our amazing bodies often beckon us down a road to health-rich returns, only to throw up a roadblock or a detour later on.

In this case, along with the damage they can cause, senescent cells do a lot of good things – important things.

Some senescent cells for example, can spot a young cancer cell that normally would grow into a tumor. The senescent cells attack and eliminate the threat.

Others can detect when nearby tissue is in some sort of trouble, and issue a call for help—sort of a cellular neighborhood watch. It’s not a great leap to accept that they may also play a part in healing wounds and other trauma. We wouldn’t want to lose those benefits.

Not surprisingly, there’s tremendous interest in finding out how anti-senescent drugs could work alongside other drugs. Though some drug-drug interactions are dangerous, others are helpful in achieving better outcomes than a single drug can achieve on its own.

Back to the labs

We can be sure that our dedicated research scientists and clinicians are exploring every possible way to get senescent cells to do their best work, while also changing their unwanted bad habits. With a little luck, today’s promising leads will turn into tomorrow’s “miracle” drugs.

References

• Hitti, Miranda. “Stopping Cancer Without Killing It” WebMD. Published March 30, 2007. Last accessed October 5, 2018.
• Hamzelou, Jessica. “Secret to old-age health could lie in purging worn-out cells” New Scientist. Published September 16, 2015. Last accessed October 5, 2018.
• Wade, Nicholas. “Purging Cells in Mice Is Found to Combat Aging Ills” New York Times. Published November 2, 2011. Last accessed October 5, 2018.
• “Senescent cells: Promising anti-aging targets for health span extension and the treatment of osteoporosis” Mayo Clinic. Published NA. Last accessed October 5, 2018.
• “Cellular Senescence Program” Mayo Clinic. Published NA. Last accessed October 5, 2018.

Last Updated: March 1, 2019
Originally Published: October 30, 2018