NK Cells

Natural Killer (NK) cells are of significant interest in relation to ageing, health and exercise, whereby their functions are severely impaired by age but with exercise and physical activity functions are often improved [49]. NK cells are predominantly associated with recognition and elimination of transformed malignant cells. However, their role has expanded to include modulation of adaptive immune responses, anti-microbial activity and resolution of inflammation [50]. Therefore, reduced NK cell function may play a pivotal role in the development of malignancy and increased viral infections seen in the old.

The majority of NK cell and exercise research has been conducted in younger individuals, with few studies assessing age or disease in relation to exercise. Increased NK cell cytotoxicity (NKCC) against the tumor cell line K562 was evident in response to 6 months of moderate intensity (50-65 % VO2max) aerobic training in old individuals [15]. However, no differences for NKCC were observed for 12 months of moderate-intensity (40-75 % VO2max) aerobic training in post-menopausal women [51]. No differences in NKCC or NK cell numbers were evident following 12 weeks of walking exercises in older sedentary women, although a highly active age-matched group had better NKCC than the sedentary women [52] . No differences were observed between physically active and inactive men, although total numbers of NK cells were higher in active men [10,53]. These results are unexpected given the relationship with increased physical fitness and cancer survivorship [54]. NK cells are highly responsive and mobile cells, rapidly mobilized during periods of homeostatic imbalance. Therefore, it is plausible that NK-cell function is not being assessed to its fullest potential. For example, baseline NK cell function may not give the full picture and instead an acute bout of exercise may be required to assess global NK cell function.

NK-cells consist of multiple sub-types which appear to mirror that of the T-cell arm, with distinct cytotoxic and regulatory properties [55]. NK cells are highly responsive to acute exercise, being mobilized from the marginal to the peripheral compartments rapidly [56]. Bigley and colleagues have recently improved the potential for assessing NK cell function using acute bouts of exercise to mobilize NK-cells, giving a more comprehensive picture of functional capacity [57,58]. Acute exercise is associated with a redistribution of NK cells with altered phenotypes and results in increased NKCC towards a number of HLA-deficient tumor cell lines [58]. A recent study by Pedersen and colleagues showed that 30 days of wheel running in mice was associated with an exercise dependent mobilization of NK cells which reduced tumor burden in 5 cancer models [59]. Unfortunately neither of these studies was conducted in older humans or animals. Until these studies are conducted in old animals or humans it remains unclear whether exercise and physical activity can override the effects of NK cell dysfunction in the old.

 
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