Effects of 6 months of moderate aerobic exercise training on immune function in the elderly

Abstract

The purpose of this study was to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and natural killer (NK) cell number and function. Previously sedentary elderly (age=65±0.8 years) subjects were randomly assigned to supervised 3 time/week exercise intervention group (EXC, n=14) or flexibility/toning control group (FT-CON, n=15). Fasting resting blood samples were drawn prior to and after the 6 month intervention. The EXC group exhibited a significant (P<0.05) 20% increase in VO₂ max, whereas the FT-CON group had a smaller non-significant (P=0.07) increase (9%). Immune results revealed that, in general, changes in immune function in response to 6 months of exercise training at an average intensity of 52% heart rate reserve (HRR) were similar when compared to FT-CON who exercised at ≈21% HRR. There were no intervention-induced changes in total white blood cell, neutrophil, lymphocyte, monocyte, eosinophil, or basophil blood counts. Furthermore, the percentage and number of CD3⁺, CD4⁺ and CD8⁺ T cells in the blood remained unchanged. There was a tendency for the percentage and number of CD4⁺ and CD8⁺ näive cells (CD45RA⁺) to increase and for CD4⁺ memory cells (CD45RO⁺) to decrease post-intervention, especially in FT-CON. Both groups exhibited a small intervention-induced increase in the T-cell proliferative response to mitogenic stimulation; the percentage change of which was higher in the EXC group at several doses of Con A. Unstimulated NK cell cytolysis versus K562 cells tended to increase (P<0.1) in the EXC group with little change in FT-CON. We conclude that 6 months of supervised exercise training can lead to nominal increases in some measures of immune function, while not affecting others, in previously sedentary elderly.

Introduction

One of the hallmarks of normal aging is the decline in several aspects of immune function (Miller, 1995). This decline is believed to be a contributing factor to the increased incidence and the aggressive course of various infections and cancers in the elderly (Mackinodan and Hirokawa, 1985). It is well known that T cell function declines with advancing age. The best characterized of these are the age-associated reductions in antigen- and mitogen-induced T cell proliferation and IL-2 synthesis and expression of high affinity IL-2 receptors (Ernst et al., 1995, Miller, 1995). Thymic atrophy and the accumulation of memory T cells (CD45RO⁺) at the expense of näive T cells (CD45RA⁺) seems to account for some of the decline in the proportion of cells that can produce and respond to IL-2 (Song et al., 1993, Miller, 1995). The effects of aging are not unique to the T lymphocyte, in that age-related effects have also been documented in other immune cells, including natural killer (NK) cells. There is a lack of consensus regarding the effects of aging on peripheral blood basal NK cell activity in elderly humans (Bloom, 1994). Basal NK cell activity in elderly humans has been reported to be higher (Krishnaraj, 1992), unchanged (Herberman and Holden, 1978), or lower (Vitale et al., 1992) than younger controls. It has recently been demonstrated that despite similar basal NK cell cytolytic ability, older people have greater numbers of NK cells than younger counterparts (Mariani et al., 1996, Woods et al., 1998) suggesting some intrinsic defect in the cytotoxic ability of NK cells obtained from the elderly.

The realization of dysregulated immune function and increased disease incidence in the elderly has been the impetus for several interventions designed to prevent, delay, or restore age-related dysregulation in immune function (Hirakowa and Utsuyama, 1989, Fagiolo et al., 1990, Yu, 1995). Unfortunately, pharmacologic/hormonal, genetic, and tissue grafting techniques have been impractical, costly to develop and administer, and most are accompanied by adverse side effects. Aside from dietary manipulation (i.e. caloric restriction, vitamin or anti-oxidant supplementation), which has been found to increase longevity and reduce cancer, attributable in part to better regulation of immune function (Meydani et al., 1995, Weindruch, 1995), research involving behavioral preventative or restorative therapies has been lacking. Alternatively, moderate aerobic exercise training has been shown to elicit beneficial outcomes in both the prevention and rehabilitation of many diseases of the elderly (Mazzeo et al., 1998) and limited preliminary evidence suggests that exercise training or a physically active lifestyle may enhance certain NK cell and T lymphocyte function in the elderly (Shinkai et al., 1997).

Several cross-sectional studies have demonstrated superior basal NK cell or T lymphocyte function in groups of elderly athletes or highly physically active people when compared to sedentary controls (Nieman et al., 1993, Shinkai et al., 1995, Gueldner et al., 1997). Unfortunately, only three prospective studies have been performed. Nieman et al. (1993) found that a 12 week moderate aerobic exercise program failed to significantly increase NK cell cytotoxicity or T lymphocyte mitogenesis in previously sedentary women. These authors suggested that this 12 week period may have been too brief to significantly alter immune function. Crist et al. (1989) found that NK cell function was higher in women who engaged in a 16 week exercise training program. However, this finding is difficult to interpret because pre-intervention measures were not taken. In addition, resistance exercise training has also failed to affect immune function in the elderly (Rall et al., 1996). As a result of the paucity of data and the overall importance to public health, we sought to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and NK cell number and function; two cell subtypes affected by aging.