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Our immune response is usually characterized as the recognition of “self” from “non-self”, or as the response to “danger signals”. Although there are some subtle distinctions between the two, we will not concern ourselves with them here. Rather, we’ll examine how the immune response works, why it is important to our survival, and how we can boost its function.


How does immunity work?

There are two ways our immune response can protect us from foreign invaders like viruses and bacteria. One is through white blood cells known as T lymphocytes or T-cells. T-cells have the uncanny ability to tell a normal cell from a cell which had been invaded by pathogens. When T-cells find cells that are not normal, for example, cells that are infected, they eliminate the offending cells. This is called cell-mediated immunity or CMI.

The other way T lymphocytes protect us is by reacting with another type of white blood cell called B lymphocytes. These cells are veritable factories of antibodies, which are proteins that circulate in the blood looking for the infectious organisms, binding with them and “neutralizing” them.

The most amazing attribute of T lymphocytes or antibodies produced by the B lymphocytes is their exquisite specificity. That is to say, if a T lymphocyte or an antibody is designed to attack a flu virus of a certain strain, it will attack this strain, and only this strain. This is, by the way, why we have to get a different flu vaccine every year; the virus mutates and, therefore, requires an antibody with a different specificity to neutralize it.

Thymus.jpgThe T-cells are formed in the thymus, an organ that is prominent in the neck area of young people but shrinks to unnoticeable proportions in as we age. T lymphocytes get their name from the thymus.

In an early stage of their development, they are “naïve”. That means they have not yet acquired their specificity. As these lymphocytes mature, however, they acquire a specificity, for example, against a specific flu virus strain. This occurs because of an actual encounter with the virus or some part of it. The result of this interaction is an “educated” T lymphocyte, a lymphocyte that can perform its function in protecting us against the flu virus.

In the human body, as in the rest of life, no resource is infinite. This is true for the pool of naïve (or non-specific) lymphocytes as well. Starting at about age 30, the thymus, where the T lymphocytes are being formed, begins to shrink (this is called involution of the thymus). As a result, the supply of naïve T lymphocytes progressively diminishes.

What that means is that older people slowly lose their capacity to mount an immune defense against new pathogens if they have not already “educated” T Lymphocytes at a younger age. To give you a real-world example: 70-80% of people between the ages of 16 and 65 will be protected from the flu if they get vaccinated; but only 30-40% of elderly people will be protected.


So what does it have to do with longevity?

In a word: Everything. The main reason for the improved longevity since the 18th century (the age of Enlightenment) is the “discovery” of the scientific method. It started with the discovery of the microscope by the Dutch scientist von Leeuwenhoek. Then there was the discovery, by a French scientist, of the connection between bacteria and disease and ways to kill them by pasteurization (yes, you probably guessed his name was Pasteur). Another milestone was the discovery of antibiotics in the 1940’s by Fleming. He received the Nobel prize for the discovery of penicillin. These were the miracles of the 19th century. In those days, old people didn’t die of cancer, they died of infections. They simply did not live long enough to develop cancers that occur related to aging.

But, you might ask, didn’t our ancestors have an immune response to protect them? Yes, they did. And indeed younger people could survive their infectious disease surprisingly well. But as their immune response started to decline after age 30, they started to succumb. Does this have any relevance to longevity in the 21st century? Yes, because when we fail to mount an immune response due to age or disease (a condition called “immunodeficiency”), drugs alone are of limited utility.


How can we boost the immune response in the elderly?

The answer to that is still being investigated. But there is research, conducted by Richard Miller and his colleagues at the University of Michigan, showing that mice on caloric restriction suffer fewer infections and live significantly longer.

But this is mice. What about men (and women)? To do an experiment on humans will be tough, long, and expensive. But researchers at the Oregon National Research Primate Center reported in the Dec.4 issue of the Proceedings of the National Academy of Sciences ( that in calorie-restricted old monkeys (30% reduction of normal diet), 30-35% of the total T-cell pool were naïve T lymphocytes. Monkeys of the same age on a regular diet had only 20-25% of these lymphocytes. This is a 50% increase in naive lymphocyte in the calorie-restricted group which is very impressive. This experiment unequivocally demonstrates that caloric restriction slows down immunological aging.

Did the boost in immunity result in increased longevity? We don’t know yet because the monkeys are still alive and kicking—so the experiment will have to continue for a longer period of time. However, mouse data from the University of Michigan, that show an increased immune capacity coupled with increased longevity, are very intriguing.


Bottom line: What shall I do?

As far as I am concerned, calorie restriction (CR) to the degree used in these experiments may not be worth the pain for ordinary humans. CR may boost my immune response. I may even live longer, but you call that living? Starving for life??

I’d much rather exercise aerobically on a regular basis for the following reasons:

  • It makes me feel better.
  • It makes my brain work better.
  • It also might help me live healthier and longer.

In addition to a good diet and exercise, I also have a couple of glasses of red wine with dinner. It tastes great and it makes me feel great. It may also make my life on earth a bit longer. But certainly, it makes my life a lot more pleasant.

Le’chaim (to life)!