IFN production ability and healthy ageing: mixed model analysis of a 24 year longitudinal study in Japan

Objective: To track changes in interferon (IFN) production in healthy individuals to shed light on the effect these changes have on the course of healthy ageing. Design: Study is based on data that were collected over 24 years from a cohort of individuals whose IFN-alpha production was quantified as a part of their annual routine health check-up. Setting: All individuals in this study underwent regular health check-ups at Louis Pasteur Center for Medical Research. Participants: 295 healthy individuals (159 males and 136 females) without a history of cancer, autoimmune diseases and hepatitis C virus (HCV) whose IFN-alpha production was quantified more than five times within 24 years were selected. Finally, 29 males and 4 females whose IFN-alpha production was quantified more than 25 times were selected and their data were analysed using a mixed model. Main outcome measures: HVJ stimulated IFN-alpha production was quantified. Healthy individual's periodical log transformed IFN-alpha values (y) were plotted versus age (x) and fitted to linear (y=mx+n) and quadratic formula (y=ax(2)+bx+c) expressions to reveal changes in the IFN-alpha production in these healthy individuals. Results: The linear expression showed that log (IFN-alpha) had a slight tendency to decline (3% over 10 years). However, the quadratic formula analysis showed the quadratic expression to be more positive than negative (a concave U-shaped pattern) which means that individuals' once declining IFN production recovered as they aged. Conclusions: Although we observed a marginal decline in IFN-alpha production, we also observed that IFN production recovered even in individuals in their mid50s to early 60s. These results combined with our previous cross-sectional studies of patients with various diseases suggest that in healthy individuals, the impairment of IFN production is triggered more by the onset of disease (notwithstanding the cause) rather than by ageing.