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Background <p>Aging is accompanied by chronic low-grade inflammation ("inflammaging"), which contributes to increased morbidity and mortality in older adults. This study evaluated the prognostic value of circulating inflammatory biomarkers, i.e. interleukin-6 (IL-6), interleukin-10 (IL-10), and CXCL9, and their integration with frailty for long-term risk stratification.</p> Methods <p>We analyzed 1,009 patients (median age, 84&#xa0;years) hospitalized in acute care wards of three Italian geriatric hospitals as part of the ReportAGE cohort. Frailty was assessed using a deficit accumulation–based Frailty Index (FI), and serum cytokines were measured by immunoassay. Cytokine-specific risk categories were combined into a composite I3 score (range, 3–9). Cox proportional hazards models adjusted for age, sex, comorbidity burden, polypharmacy, and laboratory variables were used to assess associations with 10-year mortality. In a subset of 237 patients, DNA methylation–based estimates of cytokine levels were also analyzed.</p> Results <p>Higher I3 scores were independently associated with increased mortality (hazard ratio [HR] 2.42, 95% CI 1.74–3.37 for high vs. low scores), with CXCL9 as the strongest individual predictor (HR 1.69, 95% CI 1.30–2.19). The I3 score improved risk prediction beyond FI alone, and their combination identified four distinct risk groups, with the highest mortality observed among patients with both elevated FI and I3 scores. The integrated model (Clinical variables + FI + I3) achieved the greatest discrimination during the first seven years of follow-up. Serum IL-6 and CXCL9 correlated with their DNA methylation–based estimates, supporting an epigenetic contribution to chronic inflammation.</p> Conclusions <p>The I3 score complements frailty assessment and enhances long-term mortality prediction in hospitalized older adults.</p>

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Association of an inflammaging score based on IL-6, IL-10 and CXCL9, and frailty with long-term mortality in hospitalized older adults

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月19日

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  • Matilde Sbriscia,
  • Sonia Fantone,
  • Mirko Di Rosa,
  • Francesca Marchegiani,
  • Rina Recchioni,
  • Giulia Matacchione,
  • Chiara Giordani,
  • Francesco Piacenza,
  • Robertina Giacconi,
  • Davide Gentilini,
  • Luciano Calzari,
  • Carlo Fortunato,
  • Gretta Veronica Badillo Pazmay,
  • Monia Cecati,
  • Sara Caccese,
  • Emanuele Francini,
  • Rosanna Maniscalco,
  • Maurizio Cardelli,
  • Elena Tortato,
  • Federica Lenci,
  • Yuri Rosati,
  • Maurizio Burattini,
  • Roberto Antonicelli,
  • Andrea Corsonello,
  • Luca Soraci,
  • Leonardo Biscetti,
  • Massimiliano Fedecostante,
  • Riccardo Sarzani,
  • Marco Malavolta,
  • Tiziana Casoli,
  • Maria Conte,
  • Silvia Di Valerio,
  • Angelica Giuliani,
  • Antonio Domenico Procopio,
  • Fabrizia Lattanzio,
  • Anna Rita Bonfigli,
  • Antonio Cherubini,
  • Claudio Franceschi,
  • Jacopo Sabbatinelli,
  • Fabiola Olivieri

摘要

Background

Aging is accompanied by chronic low-grade inflammation ("inflammaging"), which contributes to increased morbidity and mortality in older adults. This study evaluated the prognostic value of circulating inflammatory biomarkers, i.e. interleukin-6 (IL-6), interleukin-10 (IL-10), and CXCL9, and their integration with frailty for long-term risk stratification.

Methods

We analyzed 1,009 patients (median age, 84 years) hospitalized in acute care wards of three Italian geriatric hospitals as part of the ReportAGE cohort. Frailty was assessed using a deficit accumulation–based Frailty Index (FI), and serum cytokines were measured by immunoassay. Cytokine-specific risk categories were combined into a composite I3 score (range, 3–9). Cox proportional hazards models adjusted for age, sex, comorbidity burden, polypharmacy, and laboratory variables were used to assess associations with 10-year mortality. In a subset of 237 patients, DNA methylation–based estimates of cytokine levels were also analyzed.

Results

Higher I3 scores were independently associated with increased mortality (hazard ratio [HR] 2.42, 95% CI 1.74–3.37 for high vs. low scores), with CXCL9 as the strongest individual predictor (HR 1.69, 95% CI 1.30–2.19). The I3 score improved risk prediction beyond FI alone, and their combination identified four distinct risk groups, with the highest mortality observed among patients with both elevated FI and I3 scores. The integrated model (Clinical variables + FI + I3) achieved the greatest discrimination during the first seven years of follow-up. Serum IL-6 and CXCL9 correlated with their DNA methylation–based estimates, supporting an epigenetic contribution to chronic inflammation.

Conclusions

The I3 score complements frailty assessment and enhances long-term mortality prediction in hospitalized older adults.