Natural Killer Cell Activity in Older Adults of Varying Fitness Levels

Abstract

1060 While there is a lack of consensus regarding the effect of aging on basal (unstimulated) natural killer cell cytolytic activity (NKCA), aging reduces NKCA in response to interferon-α (IFN-α). PURPOSE: To determine if older adults of high fitness have higher NKCA than low fit elderly. We hypothesized that high-fit elderly subjects will have a higher basal and IFN-α stimulated NKCA when compared to low-fit older adults. METHODS: Twenty-three older adults (mean age 68.3 ± 5.6years) of varying fitness were recruited for this cross-sectional study. VO2max scores were obtained in response to a graded exercise treadmill test and ranged from 11.5ml/kg/min to 65.3ml/kg/min. Based upon VO2max scores, subjects were classified into high fit (n = 12, VO2max = 46.1 ± 10.9 ml/kg/min) and low fit (n = 11, 22.5 ± 4.5ml/kg/min) groups. At least one week later, peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. PBMCs were incubated for 3 hours in a 5% CO2 incubator without or with suboptimal (62.5 units/ml) and optimal (250 units/ml) concentrations of IFN-α. NK-sensitive K562 and NK-insensitive Daudi target cells were pre-labeled with 51Cr (300ìCi/10 × 106 cells) and then added to the PBMC cultures for 4 hrs. Differences in percent killing were compared for the high- and low-fit groups using t-tests. Pearson correlation coefficients between VO2max and NKCA were also calculated. RESULTS: Basal (no IFN-α) NKCA against K562 cells was 14.6 ± 5.6 and 17.3 ± 12.9, while basal NKCA against Daudi cells was 3.8 ± 5.3 and 3.2 ± 3.6 for low- and high-fit respectively. Suboptimal IFN-α stimulated NKCA against K562 cells was 24.6 ± 7.1 and 28.5 ± 11.6, while NKCA against Daudi cells was 10.4 ± 8.7 and 14.7 ± 9.8 for low- and high-fit respectively. Optimal IFN-α stimulated NKCA against K562 cells was 31.2 ± 10.6 and 33 ± 15.7, while NKCA against Daudi cells was 15.6 ± 12.5 and 20.7 ± 11.9 for low-fit and high-fit, respectively. CONCLUSION: Our results indicate that while high-fit older adults demonstrated consistently higher basal and IFN-α stimulated NKCA against K562 and Daudi targets when compared to low-fit, these values were not statistically different in t-test analyses likely due to low subject number. We also found no significant correlations between VO2max and NKCA indicating that factors other than fitness may account for higher NKCA in the high-fit group. It is unknown at this time whether the higher NKCAs seen in the high-fit group were the consequence of greater numbers of NK cells in the samples or higher NKCA on a per cell basis. Supported by NIH Grant AG-18661 to J.A. Woods