Opinion: Zombie cells may be killing you!

For a long time, scientists in the general field of microbiology believed that the cells in our bodies continuously divided, replicating themselves. Then, our immune systems cast off the old cells, and they were replaced by new, young cells. We can observe the results of this process with the naked eye as a wound heals. That’s what’s happening.

It was a nice theory about an efficient system. So, as we age, what happened to the cellular system of divide, discard, and replace? My grey hair used to be dark brown; I didn’t used to have wrinkles; my knees didn’t click when I stood after sitting.

As long ago as 1960, Leonard Hayflick, 94-year-old professor of anatomy at University of California, San Francisco, discovered a phenomenon that has become known as cellular senescence. And, like the appendix which is now a useless part of our anatomy, it may have been a valuable process that suppressed the development of cancer cells by prohibiting them from dividing.

The Hayflick Limit

Hayflick was studying cancer growth at the cellular level. He was cultivating human fetal cells and noticed that they stopped dividing after about 50 doublings. Because of this change in the expected behavior of fetal cells, he began looking at other cells. He told Laura Ungar, an Associated Press reporter, that the big surprise was that other cells stopped dividing at the same point. The phenomenon became known as the “Hayflick Limit.”

Hayflick said that his findings challenged a “60-year-old dogma” that human cells could replicate forever. Therefore, his conclusions were rejected, and he was the subject of ridicule for many years. But according to Ungar, Hayflick now says, “the field that I discovered has skyrocketed to an extent that’s beyond my ability to keep up with it.”

However, if the divide-discard-replace system stops, what happens to the undiscarded cells? For decades, scientists ignored them, assuming that they were eventually sluffed off as dead matter, in much the same way that the body rids itself of other waste. But, in a 2019 report by Krystle Barbour, Media Relations Manager for the University of Minnesota Medical School, many of the old cells become “zombie cells, because they are damaged and refuse to die.”

Zombie Cells

Barbour wrote, “As we age, these damaged cells start to accumulate and cause sterile inflammation which can alter metabolism and stem cell function, promoting aging and the conditions that are often associated with it, like Alzheimer’s Disease.” Citing research by Laura Niederhofer and Paul Robbins, she writes, “As people age, they accumulate damaged cells. When the cells get to a certain level of damage, they go through a process of their own called cellular senescence… They undergo a process of irreversible removal from the cell cycle and start releasing inflammatory factors… A younger person’s immune system is healthy and is able to clear the damaged cells, but as people age, they aren’t cleared as effectively, and they accumulate causing potential problems.”

One of the interesting things that Niederhofer and Robbins found was the variety of the cells that experience senescence. Robbins said, “What I was intrigued by was the heterogeneity of what I thought was a homogenous cell type and the ever-expanding list of the roles these cells play in disease. The list keeps growing in terms of what these cells do.”

In fact, one of the things on the list is likely one of the things that the cells, when they were younger, were intended to suppress. Nathan LeBrasseur of the Mayo Clinic says, “Senescent cells resist apoptosis, or programmed cell death, and characteristically get big and flat, with enlarged nuclei. They release a blend of molecules, some of which can trigger inflammation and harm other cells — and paradoxically also stimulate the growth of malignant cells and fuel cancer.”

Senolytics

Gaining knowledge about the process of aging and its accompanying ailments naturally led to a search for a way to stop or override cell senescence. Perhaps this is another step toward achieving “immortality” as Yuval Noah Harari predicts (see my Heartland columns, July 16 and July 23, 2022).

Ungar cites the experience of Dr. James Kirkland of the Mayo Clinic. “I got tired of prescribing better wheelchairs and incontinence devices. I wanted to do something more fundamental that could alleviate the suffering that I saw.” She said that this led him (and others) to develop medicines.

So far, most of the palliative concoctions have been used on laboratory mice, and they’ve been called “senolytics.” At the Mayo Clinic, which holds most of the patents, they’ve been shown to be effective at delaying, preventing, or easing a number of age-related disorders. But only limited trials have been allowed for a few human ailments.

Ungar wrote, “Kirkland, LeBrasseur, and colleagues did a pilot study providing initial evidence that patients with a serious lung disease might be helped by pairing a chemotherapy with a plant pigment. Another pilot study found the same combination reduced the burden of senescent cells in the fat tissue of people with diabetic kidney disease.”

LeBrasseur says that he tells the personnel in his lab that it would be wonderful if they could find a way to cure Parkinson’s, Alzheimer’s, osteoporosis, and macular degeneration, but “if we cure wrinkles, we’ll be rich, and I’ll never have to write another grant.”

Meanwhile, Richard Sollar, a 95-year-old scientist and athlete confronts his Zombie cells with exercise. In May, he competed in the Senior Games competition in Fort Lauderdale, winning five medals in track to add to his collection. As LeBrasseur says, exercise is “the most promising tool that we have” for good functioning in late life, and its power extends to our cells.”

• • •

Jim Glynn is Professor Emeritus of Sociology. He may be contacted at j_glynn@att.net.