As it turns out, judging by the reaction strength of their immune system to an unknown, but harmless, protein antigen, it’s possible for men over 70 to mount an immune response similar to that produced by much younger men -- if they get regular moderate physical activity of about six hours a week.

Previous studies show that the aging immune system suffers from a progressive decrease in function that can lead to several negative situations including increased risk of infectious disease and ineffective response to vaccination. It’s been shown that regular moderate cardiovascular exercise such as walking or cycling may offset some of the immune function decline in healthy older people. However most earlier studies tested the effect of exercise on immune function using in vitro measures of immunity, which aren’t always predictive of in vivo responses. Furthermore many earlier studies depended on antigenic challenges that weren’t novel to the subjects, which stimulated secondary or tertiary responses.

Colorado researchers use KLH for true primary immune response

Researchers at the University of Colorado-Boulder wanted to test the popularly accepted notion that people who maintain a physically active lifestyle will enjoy the benefits a stronger immune system into older age. They designed a novel in vivo challenge to the immune system. To get clean, comprehensive results, they used KLH (keyhole limpet hemocyanin), a benign T cell-dependent protein isolate that has been used extensively with animals in the past, that also is safe for humans.

The study, entitled “Influence of age and physical activity on the primary in vivo antibody and T cell-mediated responses in men,” appears in the August 2004 issue of the Journal of Applied Physiology, one of 14 peer-reviewed journals published by the American Physiological Society.

The investigative team was lead by Monika Fleshner and included Taro P. Smith and Sarah L. Kennedy, all from the Department of Integrative Physiology, University of Colorado at Boulder.

Method and results

The researchers tested almost 50 healthy, young (20-35 years of age) and older (60-79) men, some physically active and some sedentary. Using KLH overcame a major problem in many earlier age vs. exercise studies which typically utilized in vitro tests or vaccine or recall antigens to elicit an immune response. In the first stage, all subjects were “immunized” with KLH with blood collected on day one and then each week for a month. The samples were comprehensively tested by ELISA (enzyme-linked immunoabsorbent assay) for anti-KLH IgM, IgG, IgG1 and IgG2.

The second phase was three weeks later. Subjects received an intradermal injection, or skin test, of KLH with inflammation measured each day for five days to assess anti-KLH delayed-type hypersensitivity response (DTH). There was significant reduction in all anti-KLH measures with aging except for anti-KLH IgG2. The physically active older group had significantly higher anti-KLH IgM, IgG, IgG1 and DTH but not IgG2 compared with the sedentary older group.

Experiment one found that the anti-KLH IgM and IgG titers were elevated three weeks after immunization, showing that the ELISA successfully detected KLH-specific Ig and that KLH immunization induced a primary antibody response. Moreover, the KLH skin test resulted in a DTH reaction that peaked after two days, persisting up to five days. Non-immunized subjects had no inflammation, showing that the DTH reaction was specific to KLH recognition.

Discussion and conclusion

The researchers said this was the “first study to clearly demonstrate in humans by use of a novel in vivo antigenic challenge that a physical active lifestyle is associated with preventing age-associated declines in the generation of a primary antigen-specific T cell-dependent antibody and DTH responses in aging humans.”

The study found that there is an age-related decline in the primary antibody response to the novel antigen KLH as well as an age-related decline in the memory T cell response to KLH. The older physically active subject had an improved antibody and DTH response compared with older sedentary subjects that is equal to that of younger subjects. The changes in anti-KLH IgG production are primarily of the IgG1 isotype. This suggests that aging produces declines one specific T cell sub-type (Th1) that is essential for the generation of IgG1 in humans and that a physically active lifestyle in the older subjects selectively maintained the function of that specific T cell subset.

Importantly, antigen-driven responses, but not total antigen nonspecific Ig, were affected by age or exercise, suggesting this measure is truly reflecting alterations in the in vivo function of T and B-cells.

In conclusion they said the results provide in vivo evidence that physical activity is associated with maintaining a more optimal T cell-mediated response and that the DTH measure could have an important clinical implication because reductions in DTH is a predictor of mortality in the elderly and is a determinant of infectious disease risk. Furthermore, the researchers said “maintaining a physically active lifestyle improves health throughout the life span, but especially during times of immunocompromise, such as advancing age.”

They noted that although most of the regular exercisers were runners, that the type of exercise didn’t seem to matter.

Source and funding: The study, entitled “Influence of age and physical activity on the primary in vivo antibody and T cell-mediated responses in men,” appears in the August 2004 issue of the Journal of Applied Physiology, one of 14 peer-reviewed journals published by the American Physiological Society.

This study was supported by National Institutes of Health (A148557 and 2M01-RR-00051 from the General Clinical Research Center Program of the National Center for Research Resources).

Editors’ note: A copy of the research paper by Smith, Kennedy and Fleshner is available to the media. Members of the media are encouraged to obtain an electronic version and to interview members of the research team. To do so, please contact Mayer Resnick at APS 301.634.7209, cell 301.332.4402 or mresnick@the-aps.org.

APS Intersociety meeting on the INTEGRATIVE BIOLOGY OF EXERCISE

Co-sponsored by the American Physiological Society, Canadian Society for Exercise Physiology and the American College of Sports Medicine Oct. 6-9, 2004, Austin, Texas
http://www.the-aps.org/meetings/aps/austin/index.htm

The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has more than 10,000 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

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