While man’s eternal search for “the fountain of youth” continues, a study published recently in the Proceedings of the National Academy of Sciences suggests that we (at least the gourmands among us) may not like what we find. Scientists have known for decades that reducing the amount of food consumed can extend the lifespan of multiple organisms, ranging from yeast to rats. Exactly how reducing the number of calories consumed prolongs life is unknown, but theories abound. Some researchers believe that ingesting fewer calories slows down the rate at which our bodies metabolize, or break down, food and turn it into energy, thereby slowing the aging process. Others believe that decreased calorie consumption sets loose fewer free radicals, the harmful particles generated as a side effect of metabolism. The most recent theory, proposed by researchers at the National Institute on Aging (NIA), is that long term calorie cutting, or caloric restriction (CR), prolongs life in part by delaying the aging of the immune system.

One of the major health problems affecting the elderly is an increased susceptibility to infections and greater severity of disease. For instance, the yearly flu epidemic is rarely more than an inconvenience for a healthy young adult, while to an elderly person it can be life threatening. One of the many possible reasons why the elderly become more frequently and more seriously ill than the young is a gradual decline in the effectiveness of the immune system as the body ages.

What is the immune system and what does it do for us?

Your body’s immune system is responsible for fending off pathogens, or organisms that cause disease, such as bacteria, viruses and parasites. This complex and finely tuned system employs many different strategies to keep pathogens from gaining a foothold in the body and causing disease. The NIA study focused on a particular branch of the immune system, a population of immune cells called T cells, which circulate in the blood stream searching for invading pathogens. So-called “naïve T cells” are those that have never interacted with a pathogen. When a naïve T cell finds a pathogen, it signals for the destruction and clearance of the invader. The naïve T cell then turns into a “memory T cell”, which is capable of remembering and responding to that particular pathogen forever, enabling a swifter and more powerful response than can be provided by a naïve T cell.

T cells are made in a gland called the thymus. The thymus is largest in size and most active at birth, pumping out many T cells. As we age, the size and T cell-making capacity of the thymus gradually and steadily shrinks. The thymus of an elderly person generates far fewer naïve T cells than that of younger one. Additionally, the immune system of an elderly person has encountered many different pathogens over a lifetime, and more naïve T cells have become memory T cells. Since fewer naïve T cells are made by the thymus and a large portion of T cells have been converted into memory cells, the variety of new pathogens that the immune system of an elderly person can recognize is reduced. This slow decline in the ability to fight off new infections, or immune senescence, may be partly responsible for the increase in the frequency and severity of infections later in life.

The effect of reduced calorie intake on the immune system

To determine whether the life-prolonging effects of caloric restriction (CR) in monkeys were due in part to a delay in the onset of immune senescence, researchers at the NIA fed young adult monkeys either a normal diet or 30% less of the same diet, thereby decreasing caloric intake while maintaining adequate nutrition. Both sets of monkeys were maintained on their respective diets for 10 to 14 years, at which time, the monkeys’ immune systems were comparable to those of 60 to 70 year-old humans. The functioning of the monkeys’ immune systems, specifically of their T cells, was then tested over a period of three years.

In every test performed, T cells from CR monkeys showed fewer signs of aging than those of monkeys maintained on a normal diet. The CR monkeys had a higher level of naïve T cells than monkeys on the normal diet and these T cells responded to pathogens like those of a younger animal. A healthier immune system may mean that the CR monkeys can fend off pathogens and stay free of disease better than monkeys on a normal diet, although this has yet to be directly tested.

Why do we need to worry about aging and disease right now?

Aging and age-related diseases are a big concern for the medical and general communities alike. Statistics show that the number of people aged 65 and over is increasing at a faster rate than the rest of the population. It is anticipated that by 2029, people 65-74 years of age will make up 10% of the population. While 10% does not sound terribly alarming, we should keep in mind that facilities and professionals, such as nursing homes and health care providers, will have to grow in step with the aging population. Projections show that in the future, there is likely to be a shortage of health professionals, such as nurses and pharmacists, needed to take care of the elderly population. Additionally, occupancy rates for nursing home beds are already over 90% in a number of states. Looking ahead to the next few decades, it becomes clear that certain adjustments will have to be made to accommodate the elderly.

Scientific advances that can either delay or decrease immune senescence may one day enhance both quality and duration of life by helping the immune system fight off disease. So, is CR the path to a long, healthy life? While the results of this and other studies suggest that caloric restriction may be beneficial to long term health, cleaning out the fridge and going hungry may be premature. Waiting for scientists to unravel the mechanism responsible for maintaining the immune system in a youthful state while leading a healthy lifestyle, seems a more attractive option.

— Anna Kushnir, Harvard Medical School

For More Information:

Coverage of this story in “The Scientist” magazine includes quotes from the researchers involved in the immunity study. <www.the-scientist.com/news/display/37246>

For a discussion of the open question of whether caloric restriction would have any benefits for humans, see <www.harvardmagazine.com/on-line/110474.html>

Primary Literature:

Heilbronn, L.K. and E. Ravussin. 2003. Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr 78:361-369

Masoro, E.J. 2005. Overview of caloric restriction and ageing. Mech Ageing Dev 126:913-922

Messaoudi et al. 2006. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates. PNAS 103:19448-19453

National Center for Health Statistics. 2006 Health, United States, 2006 With Chartbook on Trends in the Health of Americans. Hyattsville, MD

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