Lack of Immune-resilience negatively affects Physical-resilience. Results from the InCHIANTI follow-up study

: There is consistent evidence that immune response declines with aging, with wide inter-individual variability and a still unclear relationship with the development of frailty. To address this question we assessed the role of immune resilience (capacity to restore immune functions), operationalized as the neutrophil-to-lymphocytes ratio (NL-ratio) and monocytes-to-lymphocytes ratio (ML-ratio), in the pathway that from robust status shifts to pre-frailty and frailty, and finally to death. The InCHIANTI study enrolled representative samples from the registry lists of two towns in Tuscany, Italy. Baseline data were collected in 1998, with follow up visits every three years. The 1453 participants enrolled were assessed and followed for lifestyle, clinical condition, physical performance, clinical and physiological measures. For the purpose of this analysis we used only 1022 subjects aged 65 or older at baseline. Participants in the three highest deciles of distribution for NL-ratio (>2.44) were more likely to experience a transition from robust to pre-frail, and to overt frailty status. Moreover, NL-ratio (tenth decile >3.53) and ML-ratio (tenth decile>2.02) were both predictors of mortality. These results were independent from chronological age, sex, comorbidities, and chronic low-grade inflammation assessed by high sensitivity C-reactive protein measurement. The two leucocytes-derived ratios, NL-ratio and ML-ratio, represent markers of immune resilience and predict changes in physical resilience and mortality. These biomarkers are inexpensive since based on data routinely collected in clinical practice, and can be used to assess the risk of frailty progression and mortality.