The Brain

  Overall, the hemoglobin in your blood does a decent job of regulating the oxygen levels near the individuals cells of your body so that your cells have the oxygen they need for respiration, that is, for the removal of carbon waste, but do not have so much as to kill them outright. Sometimes, however, a stray oxygen molecule does get loose from hemoglobin and must be captured before it can do any real damage to your cells or their precious cargo, the DNA.

  Cells also have evolved numerous antioxidant systems to defend you from the oxygen that you must breathe in; these antioxidant systems are so effective that they will allow you to live to be 100 years old, or older, if you are lucky. All species have had to deal with this challenge; the lifespan of virtually all species is highly correlated with how well they defend themselves from oxygen. Therefore, the best way to age slowly, and also be healthier while aging, is to expose your cells to as little oxygen as possible. One proven way to accomplish this is to need to eat as little food as possible. The most recent evidence suggests that you should focus your efforts on reducing the number of calories obtained as animal protein. The evidence to support this recommendation is overwhelming.

  During the past few decades, studies have shown that the single most important factor that determines when you will die is how long you have been alive. That sounds obvious, but it begs the question: what do you do every day that increases your chances of dying? The answer for all humans, as well as for every other respiring animal on the planet, is simple: we eat and breathe. If you consume fewer calories, namely, carbon bonds in the form of fats, proteins, and carbohydrates, you require less oxygen. However, we must eat and breathe to survive; the problem is that doing so makes us vulnerable to the consequences of oxygen. Consequently, our bodies and our brains age more rapidly because we keep eating and eating and breathing and eating and breathing all day, every day of our lives.

  Currently, scientists believe that restricting total calorie intake will not allow you to live longer; rather, reducing the total number of calories consumed each day by approximately one third will promote a healthier longevity and better quality of life.

  How does caloric restriction work?

  With normal aging, because you are eating and breathing, tissue-damaging molecules called oxygen free radicals are formed by the oxygen in your blood. Free radicals become more prevalent with age and may slowly overwhelm your natural antioxidant systems, destroying your neurons and just about every other cell in your body. According to another recent discovery, the overproduction of these oxygen free radicals may encourage cancer cells to metastasize and move around your body. Think about the unbelievable irony of this process: The biochemical processes that occur in every cell of your body are actively injuring those cells by the very process of trying to keep them alive. It turns out that each species’ maximum lifespan may be determined by how many free radicals are produced in each of their cells. To paraphrase Pogo, we have met the enemy and he is in us. There are intimate, complex, and not well-understood relationships among the actions of mitochondria within our cells, our general health, and how fast we age.

  This is worse for males. The combination of more muscle mass than women and the presence of testosterone makes men warmer than women. Testosterone alters how males metabolize food and increases the amount of heat their muscles produce during normal respiration. Testosterone turns the normal food-to-energy conversion process inefficient, that is, cells waste more energy as heat to make men feel warm. This is why it is so much easier for men to lose weight than for women; the male body, particularly the muscles, is capable of wasting a considerable number of consumed calories as body heat. Wasting calories to produce heat has negative consequences. Men need to consume more calories per day and thus produce more harmful oxygen free radicals than women do. Lacking both testosterone and significant muscle mass, women tend to produce less body heat from their food; consequently, it is much harder for women to lose weight than it is for men. In contrast, women waste less energy, need to consume fewer calories, and produce fewer oxygen free radicals—all of which benefit their overall longevity.

  In summary, because you must consume food and breathe oxygen to survive, you slowly age and die. Oxygen is the troublemaker in our lives. Species that produce fewer free radicals from the oxygen they breathe, or that have evolved better ways to handle these toxic molecules, live longer than species that have not evolved these methods. There is a strong correlation between dying and how long you have been alive. What underlies this correlation? What are you doing every day of your life that ages you? Eating and breathing. Do you have any other recourse to slow your aging process? Yes, consume foods that remove the oxygen free radicals. For obvious reasons these foods are called antioxidants.

  Antioxidant-rich foods include colorful fruit and vegetables, fish and olive oils, fruit juices, anti-inflammatory plants and drugs such as aspirin, some steroids, cinnamon and some other spices, nicotine, caffeine and chocolate, the fat-soluble vitamins, nuts, legumes, beer, and red wine. People who eat these foods do not report acute changes in their thoughts or moods (depending upon how much they consume!) but certainly benefit from consuming them regularly over their lifespan. In general, the benefit comes from the fact that all of these foods provide your brain and body with protection against the most deadly thing we expose ourselves to every day—oxygen. Thus, the lifestyles of people who live the longest are characterized by the consumption of foods rich in antioxidants as well as the consumption of far fewer calories overall. Both of these dietary approaches are healthy; when combined, they offer the best chance of a healthy life and slower aging.

  Which brain region suffers the most with aging?

  An unhealthy diet has many negative long-term consequences for brain function as we age. One of these is degeneration of the hippocampus in the temporal lobe, leading to the symptoms of dementia. There are two major consequences of the degeneration of the hippocampus: one is wandering and the other is memory loss. Sixty percent of elderly humans with dementia will wander; they forget their own name or address and become disoriented even in familiar places. Why? Recall from Chapter 1 that the hippocampus forms maps and informs you of where you are and where you live and where you parked your car. Aging alters hippocampal function; consequently, mental maps do not form correctly. Studies on mice, rats, nonhuman primates, and humans have allowed scientists to investigate what changes occur in the hippocampus during normal aging, as well as when and how they occur.

  Young rats, similar to young humans, create a map of their immediate world and store it for future use. If they find themselves in this familiar environment again, they go to the correct map drawer in their brain and use it to find their way around. In contrast, when aged rats find themselves in a familiar environment, they either fail to retrieve the correct map, or they attempt to re-map the environment from scratch. This is the main problem: errors occur in the redrawing of their map. Due to these errors, aged rats and humans alike behave as though an environment they have visited on many previous occasions is an unfamiliar one.

  Elderly humans often report similar feelings even when a spouse or friend informs them that they are in a familiar environment; this experience can be disorienting and frightening. Recall that anything that is unfamiliar will activate the amygdala (see Chapter 2) and produce a fear response. Why does the aged hippocampus fail to make accurate maps? It was once thought that the failure of the hippocampus to function normally with aging was due to massive cell loss and deterioration of neuronal connections. Today we know that the changes occurring during normal aging are far more subtle and selective. In fact, the problem with the hippocampus is due mainly to degenerative changes in a small region called the dentate gyrus.

  In elderly humans and primates, the dentate gyrus of the hippocampus shows the greatest age-related loss of function. Why is the dentate gyrus so vulnerable to aging? Research published during the past 20 years suggests that this hippocampal region experiences far more age-related infl
ammation, and inflammation-induced pathology, than any other brain region. Inflammation that develops with normal aging is not well understood, but it may be initiated by obesity, poor diet, brain trauma, diabetes, or mutant proteins. The long-term exposure of the neurons in the dentate gyrus to brain inflammation impairs normal function and prevents the brain from making new memories or new spatial maps of the environment. Brain inflammation is also present in the earliest stages of dementia. Long-term brain inflammation greatly reduces the size of the hippocampus; this leads to serious problems with learning and individuals’ ability to find their way around both new and unfamiliar environments.

  How can I reduce inflammation in my brain?

  Given the critical role of inflammation underlying these symptoms of dementia, it should not be surprising that long-term treatment with anti-inflammatory drugs, such as ibuprofen and aspirin, may protect against many of these age-related changes in brain health. Many epidemiological studies have discovered that daily use of high doses of nonsteroidal anti-inflammatory drugs, such as ibuprofen, for at least two years was associated with a significantly reduced risk of Alzheimer’s disease. Unfortunately, anti-inflammatory drugs cannot effectively treat the symptoms of Alzheimer’s disease once they have appeared nor can they reduce the extent of brain pathology associated with this disease. Furthermore, daily dosage with any of the anti-inflammatory drugs currently on the market would produce significant bleeding and discomfort in the gut.

  In addition to ibuprofen, a modest amount of alcohol every day also may help to protect your brain from developing dementia. Researchers followed 3,069 people for six years and reported that people who drank one to two drinks a day were 37% less likely to develop dementia than teetotalers. It did not matter whether their drink of choice was wine, beer, or hard liquor. The reduction in risk due to regular beer consumption was similar to that associated with exercising three times a week or more. In contrast, for people 75 years of age and older with mild cognitive impairment any amount of alcohol accelerates the rate of memory decline. Alcohol provides a good example of what scientists have learned about drugs that slow brain aging: the sooner you begin the treatment, the better the outcome.

  In spite of claims in the popular press or on the Internet, currently there is no treatment capable of stopping the deterioration of brain cells associated with normal aging. The most prevalent age-related disease associated with cognitive decline is Alzheimer’s disease; therefore, I will focus upon what you need to know about treating this disease. For most patients, the diagnosis of Alzheimer’s disease is made late in the progression of the disease. This is unfortunate because it prevents the patient from taking advantage of treatments that might slow the progression of the dementia. In addition, a better understanding of the risk factors for Alzheimer’s disease might one day reduce the incidence of the disease.

  So what are the major risk factors for Alzheimer’s disease? A family history, particularly on the female side; the presence of specific genes; major head trauma after age 50; and depression and diabetes are all well-established risk factors. A maternal history, in particular, is related to a higher risk for developing Alzheimer’s disease. A 65-year-old woman has a one-in-six chance of developing Alzheimer’s disease as compared with a one-in-eleven chance for a man of the same age. In addition, the symptoms of dementia progress more quickly in women as compared with men. Finally, elderly women are more likely than elderly men to suffer long-lasting cognitive impairments after experiencing surgical anesthesia. Women also show an additional peak onset of schizophrenia at age 50 years, which is the average age for the onset of menopause in the United States. The significant changes in body and brain physiology associated with menopause appear to place women at risk of many neurological disorders.

  Being well educated complicates the situation. First, the good news: two different studies of Catholic nuns have demonstrated that being college educated increases lifespan by about eight years, as compared with nuns who only finished high school. Being educated also delays the onset of symptoms of dementia associated with Alzheimer’s disease. However, if you do develop Alzheimer’s disease, your mental and physical decline will be accelerated, as compared with people who develop Alzheimer’s disease but did not go to college. This counterintuitive finding may be due to an imbalance in neurochemistry that is beyond the coverage of this book. Next, let us turn to another age-related disease that often coexists in many patients with Alzheimer’s disease, and which may be triggered by mutated genes as well as by an age-associated increase in brain inflammation: Parkinson’s disease.

  What is Parkinson’s disease?

  The symptoms of what is today known as Parkinson’s disease were first described in ancient texts dating back to about 2,000 B.C.E. Much later, the physician Galen called it a “shaking palsy.” Galen’s depiction was maintained by Dr. James Parkinson, a practitioner of general medicine in London who is credited with the first complete description of the symptoms and progression of the disease in 1817 in a monograph titled, “Essay on the Shaking Palsy.” The symptoms include the following: tremor or shaking that usually begins unilaterally in the hands and fingers when at rest; slowed movements with short shuffling steps; stiffness in the muscles of any part of the body, which can sometimes be quite painful; a stooped posture and balance problems with the typical risks associated with falls; an impaired ability to initiate or perform unconscious movements such as blinking, smiling, or swinging the arms when walking; and problems with speech, such as speaking too softly or hesitantly, or lacking emotional inflections. Dr. Parkinson identified nearly all of these signs and symptoms in the six patients who were discussed in his original essay, but he overlooked their muscle stiffness. Medical historians claim that Dr. Parkinson preferred not to touch his patients; instead, he used his long cane to poke at them during physical examinations and thus missed one of the critical diagnostic criteria for the disease.

  The major risk factors for Parkinson’s disease suggest the mechanisms that underlie the cause of the disease. Once again, both genes and environment play a role in this disorder. In the United States, a major risk factor is growing up in a rural environment; the cause is thought to be the early and prolonged exposure to pesticides. Other risks include exposure to heavy metals and use of an illicit opiate-like drug. A genetic risk has been identified for some families but plays little or no role for the vast majority of patients. Animal models of Parkinson’s disease have provided detailed evidence on the role of brain inflammation and subsequent oxidative stress in the death of vulnerable neurons throughout the brainstem. Although it is challenging to assign specific symptoms to the death of single neurotransmitter systems, in general, the loss of dopamine neurons underlies the motor impairments, the loss of norepinephrine neurons underlies the lethargy and low arousal levels, the loss of serotonin neurons may lead to the presence of visual hallucinations that are often reported following the cessation of some dream sleep episodes, and the loss of basal forebrain acetylcholine neurons may underlie the symptoms of dementia. This last association with acetylcholine cell loss is important because a recent study suggested that within 10 years of diagnosis almost all patients with Parkinson’s disease show some degree of dementia. Today, standard therapy involves administering drugs designed to enhance dopamine function within the synapse. Other more invasive therapies involve stimulating or lesioning specific components of the brain’s motor control systems. As we learn more about how the disease develops and progresses, safe interventional therapies likely will become more effective. Next, let us turn away from pathological aging and look at normal aging—something we all hope to experience.

  How does my nervous system change as I get older?

  Your brain loses weight. When you were born, it weighed about 360 grams; when you were 20 years old, it weighed about 1,375 grams; and, on average, it will decline to about 1,265 grams by the time you reach 80 years of age. Most of these changes are not due to cell loss but rather to the simpl
e dehydration of your brain and the subsequent shrinkage of neurons in vulnerable regions. Neurons lose their ability to function when they shrink. A minor contributor to the brain’s decrease in size is the loss of myelin insulation around axons. The loss of myelin slows down the flow of information between neurons across the brain.

  What happens to my vision?

  The visual system, which provides so much essential information to your brain, shows use-dependent age-related declines in function. The eyes develop farsightedness due to the loss of lens elasticity and the subsequent flattening of the shape of the lens, reducing the ability of the lens to accommodate focusing on close objects. The increased density, as well as opacity, of the lens also increases the minimal amount of energy needed to elicit a visual response. These changes in the lens often are accelerated by long-term exposure to bright sunlight. Due to the age-associated increasing opacity of the lens, you tend to lose sensitivity to blue light; this is most noticeable to people who undergo removal of the lens and often report that blue objects are more brilliant. The retina is a thin network of neurons at the back of the eye that detects incoming light and transduces this information into electrical impulses that are transferred to the brain for processing into images. The retina is vulnerable to many of the same age-related degenerative changes that occur in the brain, such as oxidative stress and various toxins.