Chapter 103
Maintaining the Immune System
One of the generally accepted consequences of aging is a weakening immune system. This is reflected in an increased susceptibility to acute viral and bacterial infections such as influenza and pneumococcal pneumonia. In industrialized countries, infectious diseases are the fourth most common cause of death among older people, who, compared with younger adults, die three times more often from acute infections. Compounding the problem, they respond relatively poorly to vaccinations, something known since the earliest days of vaccine development. For example, whereas influenza vaccinations can build adequate antibody protection in 50 to 75 percent of younger people, this proportion drops in older people—who need the protection most urgently—to 10 to 30 percent.
At the same time, we have known for almost 30 years that the immune cells of 80-year-olds produce significantly more proinflammatory signals. As I discuss in the chapter on inflammation, two ills come together here—a decline in the part of the immune system that fights specific infections, and an amplification of nonspecific overreactions that can trigger inflammation. We experienced this with Covid 19. Of course, older adults are more likely to live in high-risk settings such as nursing homes and have preexisting conditions that make an infection more likely and more severe, but part of their susceptibility could be due both to the waning immune system and to the potential for a hyperinflammatory “cytokine storm,” a violent immune reaction associated with worse outcomes. I have already covered inflammaging, so here I focus on immunosenescence, the decline in immune defense with increasing age, and what we can do about it. (A truly incredible overview of how the immune system works can be found in the chapter on infections in How Not to Die.)
Lifestyle
How can our daily habits influence the immune system?
Losing Weight
Obesity can impair the effectiveness of vaccinations, so that people with obesity, despite vaccination, are twice as likely to come down with influenza or flu-like infections as people of normal weight. The fact that people with obesity have more cancer could be due to impairment of their antitumor immunity.
The SOS Study (Swedish Obese Subjects, “Swedish obese subjects”) was the first controlled long-term study comparing the effects of bariatric surgery in several thousand people with the health trajectories of people who had the same weight at the start of the study but did not undergo surgery. For ten to twenty years, the weight of the control group stayed about the same, while the surgery group maintained a weight loss of about 20 percent and also suffered significantly fewer heart attacks and strokes, developed 80 percent less diabetes, and—unsurprisingly—had lower all-cause mortality. They also developed cancer less often.
Obesity significantly impairs the function of our natural killer cells, crucial members of the rapid-response unit of our immune system that fight cancer cells and virus-infected cells. In people with obesity who were randomized to a weight-loss program, there was a significant reactivation of natural killer cell function after just 90 days. The weight-loss program also had the participants exercise, so it is difficult to determine the precise effects of weight loss, because physical activity also stimulates natural killer cells.
Exercise
Physical activity can strengthen our immune system so much that the number of our sick days can be reduced by 25 to 50 percent. Natural killer cells taken after 30 minutes of cycling killed 60 percent more cancer cells in a petri dish. This could be one reason why exercise contributes both to cancer prevention and to higher cancer survival rates. Men and women over 64 who were randomized, before an influenza vaccination, to do vigorous exercise three days a week for 25 to 30 minutes for ten months achieved significantly better protection. But that does not mean you can lounge on the couch all year and then, shortly before getting vaccinated against influenza or pneumonia, jump up and take a brisk walk to get extra protection. More on how exercise strengthens the immune system and which infections exercise helps prevent according to intervention studies can be found at see.nf/exerciseimmunity.
Breathing in the Forest
Another method of lowering cortisol levels is forest bathing—going among trees can also increase natural killer cell activity, as shown in a series of randomized controlled trials that I have documented at see.nf/forestbathing. The video see.nf/treefragrance covers the volatile organic compounds produced by trees, so-called phytoncides such as pinenes, which you inhale in the forest. They enter the bloodstream and increase natural killer cell activity.
A combination of wood aromas improved recovery from stress-induced immunosuppression in mice, but is it really only the scent of the forest? Scientists investigated whether natural killer cells are activated just as much if you simply spray essential tree oil in a hotel room overnight—and it worked! These phytoncides are actually part of the tree’s own immune system, but we can use them for ourselves. Researchers suspect that these substances play a role in the fact that fewer people die of breast and prostate cancer in more heavily forested regions of Japan. It has long been known that nature helps cancer patients cope with their illness, but now it turns out that with the scent of trees it does more than just provide emotional support.
Sleep
Depending on the study, sleep deprivation in mice reduces the effectiveness of vaccines, has no effect on it, or enhances it, but consistent with the prevailing view, there is “surprisingly clear evidence” that sleep strengthens immune defenses in humans. Those who do not get enough sleep in the days immediately before and after a vaccination against hepatitis B or influenza—for example, less than six instead of seven hours—formed significantly fewer protective antibodies. This was confirmed in intervention studies with enforced sleep deprivation.
In one study, half the participants had to stay up all night after a hepatitis A vaccination. Those who were allowed to sleep normally the night after the same vaccination had twice as many antibodies in their blood a month later. Even a year later they were still significantly better protected—and because of the sleep of one night. Can’t one try to make up for this by sleeping longer on the following nights? Even then, the course has already been set. Those who were vaccinated against influenza in a week in which they were allowed only four hours of sleep per night, but then tried to catch up with twelve hours of sleep per night, still had less than half as many antibodies ten days later as a group that had gotten enough sleep from the start. Sleep deprivation, whether because you go to bed too late or get up too early, also impairs natural killer cell activity.
What about infection rates? In the Harvard Nurses’ Health Study II, it turned out that those who slept an average of only five hours per night had about a 40 percent higher risk of getting pneumonia than those who slept eight hours. People with overweight who slept too little had a risk more than 80 percent higher. Researchers at the Mayo Clinic demonstrated this even more clearly by dripping cold viruses directly into subjects’ noses: Those who reported sleeping less than seven hours per night had about a threefold higher risk of catching a cold than others who slept eight hours or more. Because self-reported sleep duration tends to be underestimated, the study was repeated using an accelerometer on the wrist for objective measurements. Participants who slept at most six hours per night had a fourfold higher risk of getting sick than others who slept seven hours or more. And that with the same infection rate, after all, the virus had been dripped directly into their noses. But the well-rested fought off the virus so quickly that the likelihood of developing symptoms was four times lower.