Brain Rules for Aging Well. John Medina
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Only certain regions contain dopamine receptors, which means only certain regions of the brain are sensitive to dopamine. One prominent area is the “Highway to Hell” circuit I mentioned. This highway consists of two small dopamine-sensitive brain regions (the ventral tegmental area and the nucleus accumbens) connected by dopamine-sensitive circuits. Over-driving this system—and thus dysregulating it—is responsible for most of the chemical addictions that regularly devour human beings.
Dopamine, it turns out, is a really big deal. And we are about to find out just how big a deal it is for seniors. One of the hallmarks of aging is that the dopamine system, after a while, begins to fade away.
The mouse that didn’t roar
Some experiments are tough to digest, like an overcooked steak, and this is one of them. You can genetically manipulate mice in such a fashion that they can’t make dopamine by themselves. When you do that, you give them a death sentence. The reason is startling. The animals starve to death. Even if you put their favorite foods in front of them, the rodent equivalent of chocolate cake, they will sit there beside the food, blinking at it, doing nothing to intervene as death slowly envelops them. Same for baby mice. Without intervention, dopamine-deficient pups won’t suckle frequently enough to sustain their little lives. They still have the behaviors necessary to look for the food and eat. They just aren’t willing to eat. Intervene by administering dopamine artificially, and everybody starts to eat normally. The point? Life without dopamine can be very difficult to sustain. Life with dopamine is, to understate the obvious, the preferred option.
The reason I bring up this experiment concerns one of the most solid biological findings that exists in the gerosciences: as humans age, the dopaminergic system begins functionally to decline. In humans, this decline has consequences much more complicated than simply changing our pleasure in eating. Since the human brain has a cortex the size of a baby blanket, and lab rodents have one the size of a postage stamp, such differences make sense.
The erosion in humans has three parts. First, the manufacture of dopamine slows down in specific regions of the brain. It’s an uneven assault. Midbrain loss is smaller, whereas loss in the forehead-dwelling dorsolateral prefrontal cortex is almost threefold greater. The effects are especially noticeable after age sixty-five. Second, dopamine receptors begin to disappear. One important receptor, dubbed D2, declines 6–7 percent with each decade of life, beginning around age twenty! Third, dopaminergic neural circuits begin flickering off, mostly because of cell death. One commonly hard-hit region is the substantia nigra, a piece of neural real estate deeply involved in motor function. Parkinson’s disease can result, which explains why one of the greatest risk factors for getting it is simply growing old.
These three categories of losses may explain virtually every behavior discussed in this chapter. Certain types of depression occur because of a loss of dopaminergic activity, for example. So common is the experience, it’s been given its own name—DDD, for dopamine deficient depression.
We also know that dopamine is involved in mediating command decisions—particularly reward prediction—which, as you recall, is a skill that diminishes with age. Dopamine mediates the willingness to take risks, which also declines. Dopamine is even associated with our psychological motivations. Given that age transports us from aggressive promotion motivation to cautious prevention motivation, we may be observing the alteration of a singular suite of risk-associated behaviors.
Even the positivity effect (and its darker twin, gullibility) may be explained by dopamine loss. We know that attentional networks, which allow us to preferentially select one set of stimuli over another, are profoundly influenced by dopaminergic activity. Indeed, most of the major players in those networks use dopamine to direct the focus of our brains. That includes the insula (coincidentally also involved in gullibility), which in youth is studded with dopamine receptors like cloves on a ham. A dysfunctional insula, by the way, is also associated with depression.
What about seniors who report being happier as they get older? Does dopamine dysregulation play a role here, too? The real answer is we don’t know. As we’ve seen in this chapter, the happiness data are nuanced, especially when other factors are considered (like diseases and depressions). Since these studies were done primarily with healthy seniors, “healthy” may also include intact dopamine pathways. In which case, scientists were studying only a subset of the population.
Or not. As we’ll see in the memory chapter, the brain is surprisingly good at conjuring up compensatory behaviors for cognitive functions it knows are eroding. The happiness data may represent the determined effort of a brain, faced with inexorable dopamine decline, refusing to go down without a fight. Or a smile. Many seniors I know still light up in the presence of chocolate cake and start looking for a fork. I’m one of them.
Awakenings
While scientists in various corners of the research world are actively investigating these processes, others have skipped ahead of the biology and gone right to the clinic. They are interested in determining what, if anything, could be done practically for patients now. If dopamine loss is so deeply associated with behavioral decline, they asked, could that decline be arrested by artificially resupplying the molecule? Research suggests there might be something to this idea.
One of the most surprising examples of this practical approach originates from a 1973 book called Awakenings, a true story written by famed neurologist Oliver Sacks, made into a movie years later.
The book wasn’t about patients suffering the consequences of aging. It was about patients suffering the consequences of infection (encephalitis). The disease left most of the patients catatonic, wheelchair bound, seemingly alive in name only. When one of these closed-for-business people (played in the movie by Robert De Niro) was administered a synthetic form of dopamine, it was like giving him a syringe filled with the Fountain of Youth. He suddenly awoke from his catatonia. He started smiling, walking, talking, wanting to fall in love—Sleeping Beauty responding to a kiss from Prince Dopamine.
This synthetic dopamine, biochemical royalty in the world of neuroscience, is called L-DOPA. (You can’t use real dopamine because it strangely refuses to jump into the brain.) L-DOPA has triggered at least two Nobel prizes, mainly for treating Parkinson’s disease. Studies have also shown positive effects on cognitive processes not associated with disease states but simply with typical aging.
Consider reward prediction, which withers with age. You can alter its fall from grace by taking L-DOPA, literally improving a complex cognitive process on the back of a simple synthetic. The effect isn’t small. The treated seniors’ laboratory performance becomes indistinguishable from that of younger, untreated controls.
L-DOPA increases your preference for looking on the Doris Day side of life, too. It elevates something called optimism bias, prejudices about which seniors know a great deal. But this experiment was not done with seniors. It was done with a younger generation, known more for loving snark than Singin’ in the Rain. It caused the author of the experiment to declare: “This study does show that optimism may be influenced by dopamine levels even in healthy people. And that’s a pretty glass-half-full kind of study.”
That’s especially good news for seniors. Optimism is not just emotional insulation against the freezing wastes of mortality. We now know that elders who have positive, even optimistic, attitudes toward their own aging live longer than those who don’t.
What do I mean by optimistic aging? A twenty-five-year-old who forgets somebody’s name seldom considers it a harbinger of Alzheimer’s disease. But if you’re older and your memory transmission slips a gear, you might very well worry about Alzheimer’s. You may become stressed, even depressed. As other roadside attractions of age come into view—from hearing loss to aching joints—your attitude may turn increasingly pessimistic. The data say: don’t go there. Seniors who take it in stride, convincing themselves the glass is still half-full, live a healthy 7.5 years longer than seniors who don’t. Optimism exerts a measurable effect on their brain. The volume of their hippocampus doesn’t shrink nearly as much as the glass-half-empty crowd’s does. That’s an important finding. The hippocampus, a sea-horse structure located just behind your ears, is involved in a wide variety