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.

Are You as Empathetic as a Rat?

Empathy is the capacity to share the emotional state of another. Politicians claim to have it when they say “I feel your pain.”

Even if they do not always show it, human beings are clearly capable of empathy. Other primates such as chimps have been observed acting in a way that is best explained by empathy. Rather than acting for their own benefit, they sometimes act because they share the feeling or distress of another chimp. Such behavior is said to be “empathy-driven.”

Once it was thought that only human beings could feel empathy. Now researchers are finding that empathy-driven behavior is more widespread than previously imagined. Not just other primates but even rodents, it seems, are biologically capable of empathy. For all the differences between the human and the rat brain, we share fundamental circuits that make it possible to feel the emotions of another, particularly when the other is in pain or distress.

In a simple experiment reported in the December 9 issue of the journal Science, researchers provide solid evidence that the much-maligned rat is capable of acting in a way that is most easily explained by empathy.

"This is the first evidence of helping behavior triggered by empathy in rats," said Jean Decety, a member of the research team at the University of Chicago. "There are a lot of ideas in the literature showing that empathy is not unique to humans, and it has been well demonstrated in apes, but in rodents it was not very clear. We put together in one series of experiments evidence of helping behavior based on empathy in rodents, and that's really the first time it's been seen," Decety said in a release issued by the University.

In order to act in a way that is empathy-driven, an animal must be capable of “emotional contagion.” To test whether rats have this capacity, an experiment was designed Chicago psychology graduate student Inbal Ben-Ami Bartal. Two rats were placed in an enclosure, one of them roaming freely while the other was locked inside a tube. The free rat, in time, could discover how to open the lock, but there was no reward for doing so.

The experiment was designed observe whether rats show they are capable of emotional contagion. Was the free rat biologically capable of emotional concern or what the paper defines as “an other-oriented emotional response elicited by and congruent with the perceived welfare of an individual in distress”?

PHOTO: ©Science/AAAS.

The free rats not only learned to open the container but did so repeatedly when it held another rat, something they did not do if it was empty or if it contained a stuffed animal.

Even more striking was their behavior when chocolate chips were involved. In one variation on the experiment, two enclosures were used, one with an enclosed rat and the other with five pieces of chocolate. The free rat has a choice: free the cagemate or eat the chocolate first. In the absence of empathy, the free rat will make the selfish choice. But at least half the time, the rat freed its cagemate first. According to the report, “these results show that the value of freeing a trapped cagemate is on par with that of accessing chocolate chips.”

"On its face, this is more than empathy, this is pro-social behavior," said Jeffrey Mogil of McGill University, who was not involved in the study. "It's more than has been shown before by a long shot.”

Without claiming to know what rats think, the authors conclude their report with their opinion that “the free rat was not simply empathetically sensitive to another rat’s distress but acted intentionally to liberate a trapped” member of their own species.

If rats are indeed capable of empathetic feelings, then it becomes clear that the biological substrate for shared emotion is deep in our evolutionary past and deep in the earlier parts of our brains. Far from being uniquely human, empathy seems to be widely shared. What is uniquely human, perhaps, is the way we override it with self-interest.

As I prepared this post, I was interrupted several times by others who were speaking of the history of racism in America and particularly the history of slavery. When I saw the pictures of rats in their enclosure, my mind went to chains and slave ships. If empathy is so deep in our mammalian evolution, so deeply rooted in our brains, what extraordinary rationalizations do we conjure up to negate it?

The paper, "Empathy and Pro-Social Behavior in Rats," is published Dec. 9 by the journal Science. http://www.sciencemag.org/content/334/6061/1427.abstract

Enhancing the Brain: A New Approach?

A molecule that protects you against viruses may also be slowing down your brain. That’s the startling finding just reported by researchers at the Baylor College of Medicine.

In the December 9 issue of Cell, a research team led by Mauro Costa-Mattioli report on how a key component of the immune system may also play a central role in the brain’s ability to form memories.

The molecule in question is the enzyme “protein kinase RNA-activated” or PKR for short. PKR is well-known to biomedical researchers. It is found in nearly all vertebrates and helps fight viral infections.

What was unknown is how PKR plays a pivotal role in regulating how the brain forms memories. Using mice, Costa-Mattioli’s team found that PKR actually slows down the brain’s ability to form memories. By blocking the production of PKR in mice, Costa-Mattioli’s team was able to produce mice with enhanced memory.

“The molecule PKR (the double-stranded RNA-activated protein kinase) was originally described as a sensor of viral infections, but its function in the brain was totally unknown," said Costa-Mattioli in a press release issued by Baylor Medical College.

The researchers used two methods to block PKR. They produced mice that were genetically modified so they couldn’t produce PKR. But they also used a drug that inhibits the production of PKR. In both cases, memory capacity was enhanced.

How does PKR act in the brain? Apparently by interacting with another key molecule, interferon-γ or IFN-γ, which is also best known for its role in the immune system. Researchers believe that in the brain, PKR and IFN-γ interact, keeping each other in balance. Suppressing PKR seems to increase the role of IFN-γ and the activity of the brain, particularly the neurons that are creating long-term memories.

“These data are totally unexpected, and show that two molecules classically known to play a role in viral infection and the immune response regulate the kind of brain activity that leads to the formation of long-term memory in the adult brain,” said Costa-Mattioli.

What is perhaps most startling about the report is that a drug that inhibits PKR enhances memory in mice. “It is indeed quite amazing that we can also enhance both memory and brain activity with a drug that specifically targets PKR,” according to Costa-Mattioli.

If a drug enhances memory capacity in mice, could it work in humans? That’s a big jump, one that will take much more research before anything is even tested in human beings. But researchers suggest that this is possible and worth exploring. Costa-Mattioli said, "More investigation is undoubtedly necessary to translate these findings to effective therapies but we would be delighted if our scientific studies were to contribute in some way to this ultimate goal."

“Our identity and uniqueness is made up of our memories," Costa-Mattioli said. "This molecule could hold the key to how we can keep our memories longer, but also how we create new ones.”

Will this provide a new strategy in dealing with diseases that rob us of our old memories and of our capacity to create new ones? Given the stakes, research will explore these possibilities.

If the research is applicable to human beings (and why not?) and if it provides a new path to preventing or delaying dementia, it will also open new ways to think about the enhancement of human cognition. The mice in the study were not suffering from any memory loss, but the speed at which they were able to learn a new task was enhanced nearly four-fold.

Given the wide-spread interest in cognitive enhancement, especially on university campuses and among transhumanists, we should expect to hear more about how inhibiting PKR just may make you smarter.

The article, "Suppression of PKR Promotes Network Excitability and Enhanced Cognition by Interferon-γ-Mediated Disinhibition,” appears in the December 9 issue of Cell.

Evolutionary Fast-Track for Human Brains

More than 35 years ago, Allan Wilson and Mary-Claire King made an astonishing proposal. Maybe what separates humans and chimps is not just our genes. Maybe it’s also how our genes are expressed or regulated.

Research published in today’s issue of PLoS Biology builds on decades of intervening advances in evolution and genetics and take the question much further. The difference between humans and nonhuman primates in cognitive ability is explained in large part by differences in gene expression, especially during the critical periods when young brains are being formed.

Humans share many of their genes with other species, especially chimps. In fact, we share so many genes that it is hard to explain how we can be so different in terms of cognitive ability. If genes make all the difference, how can they explain the differences between chimp and human brains? And how can a mere six million years of human-chimp divergence give us enough time to accumulate enough genetic change?

The answer seems to lie in the relatively rapid evolution of differences in gene expression. In other words, while the genes themselves evolved slowly, the regulation of their expression evolved more rapidly. It’s not just the genes but their expression that’s important. It’s not just the evolution of genes but the evolution of gene expression that drives the rapid divergence between human and chimp brains.

This is especially true in the genes that control the development of the prefrontal cortex of the brain. In other words, there has been relatively rapid evolution in the genetic mechanisms that regulate genes directly responsible for the early-childhood neural development of the critically-important prefrontal cortex, which is involved in abstract thinking, planning, social intelligence, and working memory.

According to the article, “humans display a 3-5 times faster evolutionary rate in divergence in developmental patterns, compared to chimpanzees.” Most important, however, is the way this research identifies specific regulators that have evolved rapidly since human-chimp divergence. These regulators are “micro-RNAs,” some of which are specifically identified in the article, with the claim that “changes in the expression of a few key regulators may have been a major driving force behind rapid evolution of the human brain.”

According to the study’s senior author, Philipp Khaitovich, this finding suggests that "identifying the exact genetic changes that made us think and act like humans might be easier than we previously imagined." Kkaitovich was quoted in a press release issued by the journal, PLoS Biology.

The article is entitled "Micro-RNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates" and appears in the December 6 issue of PLoS Biology, where it is freely available to the public.

Violence and Children's Brains

When children are exposed to violence in the family, their brains are visibly changed. That’s the disturbing message of new research published in tomorrow’s issue of Current Biology.

According to the research article, exposure to violence at home can “represent a form of environmental stress that significantly increases [the] risk of later psychopathology, including anxiety.” It’s as if violence tunes the child’s brain to expect more violence.

Earlier studies have shown that physically abused children show “selective hypervigilance to angry cues,” such as pictures of angry faces. Another earlier study used functional magnetic resonance imaging (fMRI) to show increased brain reactivity. When individuals with anxiety disorder where shown angry faces, two brain regions were overly reactive: the anterior insula (AI) and the amygdala. The same response was found in soldiers exposed to combat.

The new research takes this a step further. Children exposed to family violence, including violence between parents, also showed the same increased brain reactivity. The reaction was quite specific in that they responded to pictures of angry faces, not sad faces.

Most important, perhaps, is that this study looked at brain function rather than symptoms of anxiety or depression. In terms of behavior, the children seemed quite normal. Their brains, however, tell a different story, one of being tuned to be anxious.

Some might suggest that given all the violence in the world, the reaction is beneficial. Maybe it’s a good thing that some human beings learn to be especially responsive to potential threats.

But as the researchers note, excessive reactivity “may also constitute a latent neurobiological risk factor increasing vulnerability to psychopathology.” The researchers also found that the degree of the brain reactivity depended on the severity of the violence.

The research “underlines the importance of taking seriously the impact for a child of living in a family characterized by violence. Even if such a child is not showing overt signs of anxiety or depression, these experiences still appear to have a measurable effect at the neural level,” said Eamon McCrory of University College London, lead author, in a press release from the journal.

More than that, this research shows how violence and trauma affect human beings in ways that permanently alter the brain.

The article, “Heightened Neural Reactivity to Threat in Child Victims of Family Violence,” appears in the December 6 issue of Current Biology.

For previous work by some of these same researchers, see “The Impact of Childhood Maltreatment: A Review of Neurobiological and Genetic Factors,” published in July in Frontiers in Psychiatry.

Searching for Life on Other Planets

This post is a little bit out of my usual orbit. Literally. It has to do with newly discovered planets that orbit other suns. They’re called “extra-solar planets” or simply “exoplanets.”

Over the past twenty years, scientists have discovered nearly 700 such planets. Most of these are too big and too hot for life. Their powerful gravity and their vaporizing heat make it unlikely that any form of life could arise, much less evolve.

PHOTO CAPTION: Scientists are now starting to identify potential habitable exoplanets after nearly twenty years of the detection of the first planets around other stars. This image shows all known examples using 18 mass and temperature categories similar to a periodic table, including confirmed and unconfirmed exoplanets. Only 16 in the Terrans groups are potential habitable candidates. PHOTO CREDIT: PHL copyright UPR Arecibo

A few exoplanets may have the right conditions for life. So far, at least two exoplanets seem to have roughly “earth-like” conditions, making them what researchers call “habitable exoplanets.”

More will surely be discovered. So many more, in fact, that some sort of catalog is needed. Enter the “Habitable Exoplanets Catalog,” hosted at the University of Puerto Rico. The Catalog is being introduced on December 5, 2011 to astronomers at the Kepler Science Conference in California.

The Catalog is an online database of habitable worlds. There’s no proof yet that life exists on any of them, but many researchers believe that some forms of life will be discovered once our detection technology advances just a bit further, with probes such as NASA’s Kepler.

”New observations with ground and orbital observatories will discover thousands of exoplanets in the coming years. We expect that the analyses contained in our catalog will help to identify, organize, and compare the life potential of these discoveries,” said Abel Méndez, Director of the PHL and principal investigator of the project in a press release issued by the University of Puerto Rico.

One nice feature of the Catalog is its “periodic table of exoplanets.” Everyone remembers the periodic table of elements that hangs in every science classroom. Just as that table organizes elements by their properties, so the table of exoplanets organizes them by habitability. What’s more, because it is an online database, new discoveries are included and organized as they occur.

To achieve this, the Catalog uses data from other databases, such as the Extrasolar Planets Encyclopedia,Exoplanet Data Explorer, the NASA Kepler Mission, and other sources.

The Secret Lives of Cells Revealed

Life at the cellular level is chaotic and complex, beautiful and yet deadly.

Even though we are made up of trillions of cells, most of us give our individual cells about as much thought as a piece of sandstone thinks about individual grains of sand.

Enter the new technologies of imaging, which open new worlds. As never before, we can see the very small and the very distant.

On December 3, the American Society for Cell Biology announced the winners of the Celldance 2011 Film and Image Contest Winners.

Take a look. Unless you’re a cell biologist, it will change the way you see the world. It will re-define your relationship to your own body. It will open new vistas on the much quoted “fearfully and wonderfully made.” If only the psalmist could have seen this!

My favorite is the first place winner, “Cancer Dance.” I say “favorite” with a great deal of qualification. It’s hard to look at this film. If you know someone who has faced cancer—and who doesn’t—what you see in this film will shock and anger you. And then you have to think: cancer is happening inside all of us pretty much all the time. Fortunately, it doesn’t get the upper hand…unless it does.

When I teach the introduction to theology, I talk about God, creation, pain in nature, and human suffering at the hands of nature. Cancer is the main example. Describing this disease theologically is a real challenge. Quite simply, cancer uses the mechanisms of life to destroy lives. It turns everything good bad.

I once asked an oncologist friend who is a Christian: “When you look at a cancer cell, theologically, what do you see?” He was so astounded by the question that he couldn’t answer.

Now, thanks to this video, you can ask yourself that question. Theologically, what is going on here? What the bleep is going on here? Why would God design such a system?

So from now on, when I teach theology, I’ll run the video. I won’t have answers. I will hope my students will learn that their standard answers might not be so useful after all.

Finally let me add that I am looking forward to the publication of a book called Chance, Necessity, Love: An Evolutionary Theology of Cancer. It’s the work of Leonard M. Hummel, who teaches Pastoral Theology and Care at the Lutheran Theological Seminary at Gettysburg, and Steve James, Associate Professor of Molecular Biology at Gettysburg College. I’ll update when the book is available.

Here again is the LINK to the videos. Each one is a winner. We nonscientists owe a great debt to the hardworking young researchers who spent hours showing us what we’re made of. For a theologian, it's a revelation.

Cognitive Enhancement: Campus Update

Use of drugs to boost academic performance is nothing new, but The Washington Post has just published a news story suggesting that use of these drugs is increasing on college campuses.

The story, written by Post reporter Jenna Johnson, refers to a study at the University of Maryland that suggests that students who take cognitive enhancers study less, party more, and have slightly lower grade point averages than their classmates. That suggests that their main purpose for using the drugs is stay competitive without letting studies get in the way of college.

There is little doubt, however, that the drugs are also being used by highly focused, academically competitive students in demanding programs. Their purpose: to add an edge to their hard work in order to stay in the top one or two percent of the competitive pile. As the Post reports, one name for these drugs is “Ivy League crack.”

The drugs in question are familiar enough—mostly Ritalin and Adderall. Students without prescriptions can easily buy these drugs from other students.

Should use of these drugs be treated as crimes? Or should those who wish to excel academically be allowed to use whatever means helps them achieve that end? For more on that debate, see the now-classic 2008 article in the journal Nature, in which prominent bioethicists such as Stanford’s Henry Greely argue for greater tolerance and openness.

Science and Technology in Theological Perspective

Most of the time, my posts address the latest developments in key areas of science and technology.

Occasionally, it’s helpful to stand back and ask whether it is possible to put these developments together into a broader picture. The speed of scientific discovery can make our heads spin. Can we put things together? Is it possible to offer a theologically coherent view of science and technology today?

One of the boldest attempts along this line is the “Pastoral Letter” released by the United Church of Christ early in 2008. The full title of the Letter is "A New Voice Arising: A Pastoral Letter on Faith Engaging Science and Technology."

When the Letter first appeared, one person to recommend it was Alan Leshner, Executive at the American Association for the Advancement of Science. He wrote:

I am delighted to see the United Church of Christ's clear support of science. I believe that science and religion are complementary to each other, and should not be seen as competing ways of looking at the world; they are concerned with different questions. In an era of such rapid science and technology advances – advances that bring benefits as well as, at times, risks -- and when science and technology are becoming ever-more imbedded in every aspect of modern life, it is essential that we maintain an active dialogue among scientists, ethicists, and religious communities. In the same way that UCC states that it cannot ignore the context in which it functions, neither can the scientific community ignore its societal context. For this reason, we see a dialogue between science and religion as vital.

While science and technology have continued to advance rapidly since 2008, the themes expressed in the Letter remain current. Church groups have used it as a study document. Clergy have used it for sermons. My guess is that they will continue to do so.