Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol

Abstract Background Infectious diseases are among the most common causes of hospitalization in older adults and may lead to a high burden on the individual’s health and healthcare system. However, it is unclear whether and to which extent these events might affect frailty, fastening its development...

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Main Authors: Wenxiang Guo, Leonardo Bencivenga, Bruno Micael Zanforlini, Chiara Curreri, Maria Cristina Ferrara, Benedetta Maisano, Luca Tinelli, Laura Andreea Ceparano, Raffaella Merenda, Chiara Cosma, Lucia Manfron, Nicolò Gentili, Silvia Sturani, Monica Cardi, Alice Campion, Benedetta Berardi, Martina Lombardi, Elisabetta D’Aversa, Francesca Salvatori, Veronica Tisato, Joanne Vanessa Vargas, Grazia Daniela Femminella, Donato Gemmati, Giuseppe Sergi, Giuseppe Bellelli, Paolo Mazzola, Caterina Trevisan, Stefano Volpato, the INFRAGEN working group
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Language:English
Published: BMC 2025-07-01
Series:BMC Geriatrics
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Online Access:https://doi.org/10.1186/s12877-025-06194-z
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author Wenxiang Guo
Leonardo Bencivenga
Bruno Micael Zanforlini
Chiara Curreri
Maria Cristina Ferrara
Benedetta Maisano
Luca Tinelli
Laura Andreea Ceparano
Raffaella Merenda
Chiara Cosma
Lucia Manfron
Nicolò Gentili
Silvia Sturani
Monica Cardi
Alice Campion
Benedetta Berardi
Martina Lombardi
Elisabetta D’Aversa
Francesca Salvatori
Veronica Tisato
Joanne Vanessa Vargas
Grazia Daniela Femminella
Donato Gemmati
Giuseppe Sergi
Giuseppe Bellelli
Paolo Mazzola
Caterina Trevisan
Stefano Volpato
the INFRAGEN working group
author_facet Wenxiang Guo
Leonardo Bencivenga
Bruno Micael Zanforlini
Chiara Curreri
Maria Cristina Ferrara
Benedetta Maisano
Luca Tinelli
Laura Andreea Ceparano
Raffaella Merenda
Chiara Cosma
Lucia Manfron
Nicolò Gentili
Silvia Sturani
Monica Cardi
Alice Campion
Benedetta Berardi
Martina Lombardi
Elisabetta D’Aversa
Francesca Salvatori
Veronica Tisato
Joanne Vanessa Vargas
Grazia Daniela Femminella
Donato Gemmati
Giuseppe Sergi
Giuseppe Bellelli
Paolo Mazzola
Caterina Trevisan
Stefano Volpato
the INFRAGEN working group
author_sort Wenxiang Guo
collection DOAJ
description Abstract Background Infectious diseases are among the most common causes of hospitalization in older adults and may lead to a high burden on the individual’s health and healthcare system. However, it is unclear whether and to which extent these events might affect frailty, fastening its development or hampering its reversion. The aims of the INFRAGEN project are 1) to assess the impact of acute infections on frailty trajectories in older inpatients, and 2) to evaluate the modifying effect of sociodemographic, clinical, functional, and genetic/epigenetic factors on that association. Methods INFRAGEN is a multicenter prospective observational study that will be conducted in the acute Geriatric Units of four Italian centers (Ferrara, Padova, Monza, and Napoli). The project will involve individuals aged ≥ 70 with no or mild-to-moderate pre-admission frailty (Clinical Frailty Scale [CFS] < 6) and diagnosis of acute infectious diseases at the time of hospital admission or during hospitalization. For each participant, we will record data concerning the multidimensional geriatric assessment and the type and severity of infectious diseases (diagnosed according to ICD-9 codes). Blood samples will be collected to assess Global DNA methylation, Leukocyte Telomere Length (LTL), and levels of circulating markers associated with biological processes related to frailty (inflammatory state, dysmetabolism, brain modifications, and oxidative stress). Frailty status will be evaluated through the CFS and Frailty Index at admission (referring to the 2 weeks before hospitalization), hospital discharge, and after 3 months. In a subsample, genetic/epigenetic analyses will also be performed at the 3-month follow-up. Discussion INFRAGEN will contribute to exploring the complex pathophysiologic mechanisms of frailty in the context of infections in older adults through a translational approach. Trial registrations NCT06430073 (ClinicalTrials.gov); Registration date: 2024–05-28.
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spelling doaj-art-11dc1d6b56b945da9c42e24e07e039012025-08-20T03:06:04ZengBMCBMC Geriatrics1471-23182025-07-012511710.1186/s12877-025-06194-zEffect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocolWenxiang Guo0Leonardo Bencivenga1Bruno Micael Zanforlini2Chiara Curreri3Maria Cristina Ferrara4Benedetta Maisano5Luca Tinelli6Laura Andreea Ceparano7Raffaella Merenda8Chiara Cosma9Lucia Manfron10Nicolò Gentili11Silvia Sturani12Monica Cardi13Alice Campion14Benedetta Berardi15Martina Lombardi16Elisabetta D’Aversa17Francesca Salvatori18Veronica Tisato19Joanne Vanessa Vargas20Grazia Daniela Femminella21Donato Gemmati22Giuseppe Sergi23Giuseppe Bellelli24Paolo Mazzola25Caterina Trevisan26Stefano Volpato27the INFRAGEN working groupSchool of Medicine and Surgery, University of Milano-BicoccaDepartment of Translational Medical Sciences, University of Naples “Federico II”Department of Medicine (DIMED), University of PaduaDepartment of Medicine (DIMED), University of PaduaSchool of Medicine and Surgery, University of Milano-BicoccaSchool of Medicine and Surgery, University of Milano-BicoccaSchool of Medicine and Surgery, University of Milano-BicoccaDepartment of Translational Medical Sciences, University of Naples “Federico II”Department of Translational Medical Sciences, University of Naples “Federico II”Department of Medicine (DIMED), University of PaduaDepartment of Medicine (DIMED), University of PaduaDepartment of Medicine (DIMED), University of PaduaDepartment of Medicine (DIMED), University of PaduaDepartment of Medical Science, University of FerraraDepartment of Medical Science, University of FerraraDepartment of Medical Science, University of FerraraDepartment of Medical Science, University of FerraraDepartment of Translational Medicine, University of FerraraDepartment of Translational Medicine, University of FerraraDepartment of Translational Medicine, University of FerraraDepartment of Translational Medicine, University of FerraraDepartment of Translational Medical Sciences, University of Naples “Federico II”Department of Translational Medicine, University of FerraraDepartment of Medicine (DIMED), University of PaduaSchool of Medicine and Surgery, University of Milano-BicoccaSchool of Medicine and Surgery, University of Milano-BicoccaDepartment of Medical Science, University of FerraraDepartment of Medical Science, University of FerraraAbstract Background Infectious diseases are among the most common causes of hospitalization in older adults and may lead to a high burden on the individual’s health and healthcare system. However, it is unclear whether and to which extent these events might affect frailty, fastening its development or hampering its reversion. The aims of the INFRAGEN project are 1) to assess the impact of acute infections on frailty trajectories in older inpatients, and 2) to evaluate the modifying effect of sociodemographic, clinical, functional, and genetic/epigenetic factors on that association. Methods INFRAGEN is a multicenter prospective observational study that will be conducted in the acute Geriatric Units of four Italian centers (Ferrara, Padova, Monza, and Napoli). The project will involve individuals aged ≥ 70 with no or mild-to-moderate pre-admission frailty (Clinical Frailty Scale [CFS] < 6) and diagnosis of acute infectious diseases at the time of hospital admission or during hospitalization. For each participant, we will record data concerning the multidimensional geriatric assessment and the type and severity of infectious diseases (diagnosed according to ICD-9 codes). Blood samples will be collected to assess Global DNA methylation, Leukocyte Telomere Length (LTL), and levels of circulating markers associated with biological processes related to frailty (inflammatory state, dysmetabolism, brain modifications, and oxidative stress). Frailty status will be evaluated through the CFS and Frailty Index at admission (referring to the 2 weeks before hospitalization), hospital discharge, and after 3 months. In a subsample, genetic/epigenetic analyses will also be performed at the 3-month follow-up. Discussion INFRAGEN will contribute to exploring the complex pathophysiologic mechanisms of frailty in the context of infections in older adults through a translational approach. Trial registrations NCT06430073 (ClinicalTrials.gov); Registration date: 2024–05-28.https://doi.org/10.1186/s12877-025-06194-zFrailtyInfectionsEpigenetic factorsGeneticsInflammation mediatorsLongitudinal study
spellingShingle Wenxiang Guo
Leonardo Bencivenga
Bruno Micael Zanforlini
Chiara Curreri
Maria Cristina Ferrara
Benedetta Maisano
Luca Tinelli
Laura Andreea Ceparano
Raffaella Merenda
Chiara Cosma
Lucia Manfron
Nicolò Gentili
Silvia Sturani
Monica Cardi
Alice Campion
Benedetta Berardi
Martina Lombardi
Elisabetta D’Aversa
Francesca Salvatori
Veronica Tisato
Joanne Vanessa Vargas
Grazia Daniela Femminella
Donato Gemmati
Giuseppe Sergi
Giuseppe Bellelli
Paolo Mazzola
Caterina Trevisan
Stefano Volpato
the INFRAGEN working group
Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol
BMC Geriatrics
Frailty
Infections
Epigenetic factors
Genetics
Inflammation mediators
Longitudinal study
title Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol
title_full Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol
title_fullStr Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol
title_full_unstemmed Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol
title_short Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol
title_sort effect of infections dna methylation and telomere length on frailty trajectories in hospitalized older patients the infragen study protocol
topic Frailty
Infections
Epigenetic factors
Genetics
Inflammation mediators
Longitudinal study
url https://doi.org/10.1186/s12877-025-06194-z
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