Is Aging a Disease of Stem Cells?

Is aging a disease? And if it is a disease, what “causes” it? Is it simply natural for bodies to age over time, or is something wrong with them, something that could be “fixed”?

In a report in the January 3 issue of Nature Communications, researchers at the University of Pittsburgh School of Medicine report on work with mice that are bred especially to age quickly. The mice have a version of progeria, a disease in humans that causes children to age well before their time.

The research team looked at differences in stem cells or progenitor cells, which healthy bodies naturally keep in reserve as a source for new cells to replace worn-out cells. Not surprisingly, they found that the progeria mice had fewer progenitor cells than their healthy counterparts. What’s more, the few progenitor cells in the progeria mice failed to function normally. For example, they didn’t produce replacement cells as needed.

If that’s the problem, can it be “fixed”? The researchers, led by senior investigators Johnny Huard and Laura Niedernhofer, injected the rapidly-aging progeria mice with progenitor cells from the muscles of healthy mice. The result was pretty amazing.

"We wanted to see if we could rescue these rapidly aging animals, so we injected stem/progenitor cells from young, healthy mice into the abdomens of 17-day-old progeria mice," Dr. Huard said in a press release issued by the University of Pittsburgh. "Typically the progeria mice die at around 21 to 28 days of age, but the treated animals lived far longer—some even lived beyond 66 days. They also were in better general health."

How did this work? Did the injected cells start producing replacement cells? Possibly, but the main effect of the injected cells seems to have been to change the host cells in the body of the progeria mice. In other words, the injected healthy progenitor cells changed the progeria mouse’s own cells into more healthy, more normal cells.

"This leads us to think that healthy cells secrete factors to create an environment that help correct the dysfunction present in the native stem cell population and aged tissue," Dr. Niedernhofer said. "In a culture dish experiment, we put young stem cells close to, but not touching, progeria stem cells, and the unhealthy cells functionally improved." Fascinating!

What about mice that are aging normally? Would the injection of progenitor cells from younger mice, for example, also “rescue” non-progeria but aging mice?

Whether anything like this could be done safely in human beings is a big question that will require a lot more research. It may turn out that injecting progenitor cells into a human patient with premature aging might help stall the aging but might also create other problems, such as cancer. In time, it may be possible to get the benefits while managing the risks.

The Pitt research, although dealing with mice with progeria, opens profound questions about humanity, aging, enhancement, and the possibility of extending the human lifespan.

The biggest question of all is whether something like this would slow the aging process in normal or healthy human beings. In other words, is this yet another possible pathway to human enhancement? Could this be used to “treat aging as a disease”?

Is aging a disease? Dr. Niedernhofer’s comment is revealing: "Our experiments showed that mice that have progeria, a disorder of premature aging, were healthier and lived longer after an injection of stem cells from young, healthy animals," Dr. Niedernhofer said. "That tells us that stem cell dysfunction is a cause of the changes we see with aging." A dysfunction? A disease? A difference?

On the question of religion and the morality of extending the human lifespan, probably the best book on the market is Religion and the Implications of Radical Life Extension, edited by Calvin Mercer and Derek Maher. I have an essay in the book reflecting on the question from the standpoint of Christianity.

My take? Extending the human lifespan is not immoral or obviously wrong, but Christians hope for a transformation, not an extension. More of the same is too little.

The report appeared in the January 3 issue of Nature Communications. It is entitled Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model and is available free to the public.

Eating, Aging, and the Brain

Two recent studies shed new light on the relationship between food and the brain.

The first study involves mice on a calorie-restricted diet. Restricting calories to about 70% of normal intake kept the mice—and their rodent brains—young when compared to control mice who could eat whenever they wanted. And while there’s no proof yet that this works with human beings, there is a lot of interest by researchers in finding out what is going on in the relationship between aging and eating.

The latest research is reported in the December 19 of PNAS. Researchers at the Catholic University of Sacred Heart in Rome report their finding that a naturally-occurring protein, CREB1, plays a key role in mediating between caloric restriction and the delay of aging. Caloric restriction seems to trigger CREB1, which in turn activates many other genes involved in longevity and brain function.

What is new in this research is the relationship between caloric restriction and CREB1 activity. Discovering how these molecules interact opens the possibility that the activity of CREB1 can be increased without having to keep to a fairly austere diet.

According to Giovambattista Pani, one of the lead researchers, “Our hope is to find a way to activate CREB1, for example through new drugs, so to keep the brain young without the need of a strict diet.”

“This discovery has important implications to develop future therapies to keep our brain young and prevent brain degeneration and the aging process. In addition, our study shed light on the correlation among metabolic diseases as diabetes and obesity and the decline in cognitive activities,” according to Dr. Pani.

The second study is published in the December 28 issue of Neurology and does involve human beings. Just in time for New Year’s resolutions, researchers at Oregon State University report on the brains and the diets of 104 seniors with an average age of 87. The result is pretty sobering. Those who ate fast foods and snack loaded with trans-fats scored much worse on cognitive tests than those who ate diets rich in the healthy oils commonly found in fish or consumed high levels of vitamins B, C, D, and E.

How much worse? The fast-food seniors scored 17% lower on thinking and memory tests and had a shocking 37% lower active brain size based on an MRI. And that’s after other factors such as age or education level are removed. Diet alone, it appears, makes a significant difference. Eating the right food seems to help slow down the age-related shrinkage of the brain.

Someday there might be a pill that makes us and our brains resist aging. For now, it’s what we eat that counts. These results need to be confirmed, but obviously it is very exciting to think that people could potentially stop their brains from shrinking and keep them sharp by adjusting their diet," according to Gene Bowman of the Oregon Health & Science University in Portland and author of the study.

This would not have surprised Saint Athanasius, bishop of Alexandria in the mid-4th century. Like many of his age, Athanasius was fascinated by the story of Saint Anthony of Egypt, one of the earliest Christian ascetics. Athanasius wrote a spiritual biography of Anthony, interpreting his life and turning him into the prototype of Christian monks.

Anthony gave away the family fortune and lived in isolation in the Egyptian desert, eating almost nothing. The result? He lived to 105 and was known for his wisdom to the very end.

Todd Daly has written about Athanasius and Anthony, including an essay in my recent book, Transhumanism and Transcendence. Daly makes it clear that Anthony’s purpose was not longevity or a youthful brain. This is no science experiment, and if Anthony is the first monk, he’s not the first transhumanist. But according to Athanasius (and to Daly), Anthony is conducting a spiritual experiment. His question is whether it is possible to regain some small portion of the original human condition…humanity as God intended, in other words, rather than the fallen humanity we experience. By denying his body, he sought to expand his soul. Without realizing it, he kept his brain from shrinking.

The amazing thing is that by asking a seemingly arcane theological question—and by sticking with it for decades—Anthony anticipates today’s research.

The PNAS article was published on December 19. The Oregon study was published online on December 28 by the journal Neurology.