This study explored whether three biomarkers from different biological pathways (ie, lipid peroxidation, platelet activation, and inflammation) were associated with the onset of (severe) mobility disability and mortality in a large sample of community-dwelling older persons. We found that IL-6 concentrations were consistently associated with major health-related events, even after adjustment for several potential confounders. Independent associations were also reported between urinary concentrations of 8-iso-PGF2α and 11-dehydro-TXB2 with mortality.
Overall, our study confirms the importance of IL-6 as a valuable and clinically meaningful biomarker for gerontology and geriatric medicine (25
). In fact, IL-6 concentrations have shown to significantly predict subclinical (eg, sarcopenia, body composition modifications, insulin resistance) (26
) as well as clinical (eg, physical impairment, disability, mortality) (28
) conditions in older persons. Interestingly, the strength of the association we reported between IL-6 and mortality was not significantly modified by the inclusion of potential confounders in the adjusted models. This finding suggests this proinflammatory cytokine is related to mortality independent of the presence of common clinical conditions and disease risk factors (thus, strengthening the clinical relevance of IL-6 as prognostic indicator).
To our knowledge, this is the first study testing lipid peroxidation and platelet activation biomarkers for the prediction of incident mobility disability and mortality events in older persons. Several studies have previously reported that 8-iso-PGF2α
are particularly elevated in selected populations, such as subjects with increased cardiovascular risk (10
). It is noteworthy that cardiovascular disease is not only the leading cause of death in Western countries, but also detrimental to successful aging (36
). Moreover, both 8-iso-PGF2α
have been shown to be closely related to a wide spectrum of subclinical (eg, body composition modifications, insulin resistance, inflammation) (10
) and clinical (eg, obesity, diabetes, pulmonary diseases, hypercholesterolemia, hypertension) (10
) conditions potentially contributing to the onset of disability and mortality. Whereas we found statistically significant relationships between both 8-iso-PGF2α
and mortality, no significant associations were reported for the mobility outcomes. However, given the novelty of the study, our results cannot still be considered as definitive. In fact, although we cannot exclude these biological pathways as unrelated to the disabling process, a large amount of evidence still supports the involvement of increased oxidative damage and platelet activity in several age-related modifications responsible for negative health-related events (including physical decline) (16
). Therefore, it may simply be that 8-iso-PGF2α
do not directly influence the onset of disability, although different biomarkers from the same biological pathways may still be predictive of the outcomes we tested. Our negative results for 8-iso-PGF2α
may also be due to the older age of our sample compared with previous studies examining these biomarkers. It is possible that aging may decrease the prognostic value of these biomarkers through the increasing number of endogenous and exogenous confounders that accompany age. It is also possible, taking into account the lack of significant age interactions on the studied relationships and the Health ABC study inclusion/exclusion criteria, that our sample may be composed by successful agers and not representative of the general older population.
Some limitations of the present study need to be mentioned. It might be that our sample population may not be representative of older persons and potentially departure from normal aging. Differently from 8-iso-PGF2α and 11-dehydro-TXB2, significant results have already been obtained for IL-6 on the mobility outcomes. This statistical significance for IL-6 may suggest that the nonsignificant findings obtained by the other two biomarkers are indeed true negative results. Our analyses are based on single time-point assessments of the studied biomarkers. This might not be sufficient to adequately represent the participants’ true underlying stress state. Moreover, these are single biomarkers of extremely complex (and interacting) pathways. Thus, we cannot categorically exclude that lipid peroxidation and platelet activation may still be involved in the pathophysiological mechanisms underlying the onset of mobility disability.
In conclusion, our findings confirm the strong association of IL-6 concentrations with the onset of major negative health-related events in older persons. Increased urinary concentrations of 8-iso-PGF2α and 11-dehydro-TXB2 are associated with a higher mortality risk. Further studies confirming our findings and exploring the predictive value for health-related events of other biomarkers of oxidative damage and platelet activation in older persons are needed.