Department of Scientific Research, Campus Ludes, Off-Campus Semmelweis University, Lugano-Pazzallo, Switzerland.
Santa Chiara Institute, Lecce, Italy.
J Gerontol A Biol Sci Med Sci. 2024 May 1;79(5). doi: 10.1093/gerona/glae076.
There is consistent evidence that immune response declines with aging, with wide interindividual 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 2 towns in Tuscany, Italy. Baseline data were collected in 1998, with follow-up visits every 3 years. The 1 453 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 1 022 subjects aged 65 or older at baseline. Participants in the 3 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 of chronological age, sex, comorbidities, and chronic low-grade inflammation assessed by high sensitivity C-reactive protein measurement. The 2 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 because they are based on data routinely collected in clinical practice and can be used to assess the risk of frailty progression and mortality. Clinical Trials Registration Number: NCT01331512.
有确凿的证据表明，免疫反应随着年龄的增长而下降，个体间差异很大，与虚弱的发展关系仍不清楚。为了解决这个问题，我们评估了免疫弹性（恢复免疫功能的能力）的作用，其表现为中性粒细胞与淋巴细胞比值（NL-ratio）和单核细胞与淋巴细胞比值（ML-ratio），在从强壮状态向衰弱前期和衰弱状态转变，最终向死亡的途径中发挥作用。InCHIANTI 研究从意大利托斯卡纳的两个城镇的登记名单中抽取了有代表性的样本。1998 年收集了基线数据，并每 3 年进行一次随访。共纳入了 1453 名参与者，对他们的生活方式、临床状况、身体机能、临床和生理指标进行了评估和随访。为了进行这项分析，我们仅使用了基线时年龄在 65 岁或以上的 1022 名参与者。NL-ratio（分布的前 3 个十分位数>2.44）较高的参与者更有可能从强壮状态转变为衰弱前期，并且出现明显的衰弱状态。此外，NL-ratio（第 10 个十分位数>3.53）和 ML-ratio（第 10 个十分位数>2.02）均为死亡的预测因素。这些结果独立于年龄、性别、合并症和通过高敏 C 反应蛋白测量评估的慢性低度炎症。这两个白细胞衍生的比值，NL-ratio 和 ML-ratio，代表免疫弹性的标志物，可预测身体弹性的变化和死亡率。这些生物标志物价格低廉，因为它们基于临床实践中常规收集的数据，可以用于评估衰弱进展和死亡的风险。临床试验注册号：NCT01331512。
