Leader: Patrizia Rovere-Querini (UNISR); Other collaborator(s):
DAMPs as novel targets to interfere with aging trajectories. The investigation of sarcopenia, a multifactorial determinant of age-related morbidity, and of underlying inflammaging circuits may disclose pathomechanisms and tools for risk stratification. Damage-associated molecular patterns (DAMPs), released by damaged/dying cells, are key mediators of sterile inflammation that hold potential as novel biomarkers, e.g., HMGB1, implicated in muscle waste in cancer patients, but still unexplored in age-related sarcopenia. We plan to study DAMPs as serum biomarkers, in association with functional and imaging-related correlates to stratify clinical phenotypes and predict sarcopenia, disability and frailty in a large cohort of geriatric patients.
Brief description of the activities and of the intermediate results: In November and December 2023 we participated in coordination meetings with the other Spoke 3 partners. Organization of the activities. Performance of the multidimensional geriatric evaluations and blood biobank. From January we performed the multidimensional geriatric evaluations and biobank of the community dwelling volunteers previously enrolled in the FRASNET study. This is the cohort in which we are going to study the biomarkers of inflammation.
Main policy, industrial and scientific implications: Better definition of targets that could interfere with ageing trajectories.
Due to budget constraints, we shifted from the initial plan to measure damage-associated molecular patterns (DAMPs) for stratifying aging trajectories. Instead, we will measure GDF-15 in conjunction with multidimensional geriatric evaluations to stratify clinical phenotypes and predict sarcopenia, disability, and frailty in a large cohort of older individuals.
We continue to perform multidimensional geriatric evaluations (including blood sample collection and biobanking) in a large cohort of geriatric and neurologic patients.
We continue to perform multidimensional geriatric evaluations (including blood sample collection and biobanking) in a large cohort of geriatric and neurologic patients. We have now completed 222 visits of participants previously enrolled in the FRASNET study and 51 patients affected by cognitive impairment.
We have started the dosage of GDF15 though the Ella method in 144 patients.
We continue to perform multidimensional geriatric evaluations (including blood sample collection and biobanking) in a large cohort of geriatric and neurologic patients.
We have completed the dosage of GDF15 though the Ella method in both geriatric and neurologic patients.
The dosage of GDF-15 was performed in a group of 52 individuals whose samples were collected in both 2017-2019 and 2023-2024. The median age of this subgroup was 76 years, with 38.5% being male. The median Body Mass Index was 26.7, and the prevalence of frailty was 21%, with a median frailty index of 0.13. Cognitive performance in this group was generally high, with a median Mini-Mental State Examination score of 29, while nutritional status was good, indicated by a median Mini Nutritional Assessment Short Form score of 14. Among participants, 54.55% were classified as robust, 13.5% as pre-sarcopenic, and 4.55% as sarcopenic and obese. GDF15 determination was conducted using the ELLA method. No significant sex-based differences were observed in GDF-15 levels.
GDF15 levels were found to be cross-sectionally associated with an increased risk of physical frailty (as defined by the frailty phenotype), greater fatigue, and poorer physical performance at baseline. Additionally, during follow-up visits, GDF15 levels were cross-sectionally associated with poorer balance and lower physical activity levels in older adults. Longitudinally, elevated GDF15 levels were linked to an increased risk of sarcopenia, lower physical activity levels, and poorer physical performance.
These findings support the potential use of GDF-15 for the early prediction of sarcopenia risk in aging populations and for guiding personalized preventive interventions aimed at mitigating functional decline.
From April to July 2025, the team made steady progress in advancing the scientific validation and dissemination of emerging GDF15 as biomarker associated with aging-related conditions, particularly frailty, sarcopenia, and malnutrition. In April 2025 the team prepared an abstract titled “GDF-15, sRAGE, FGF21, and NfL: Novel Biomarkers in Malnutrition” for submission to the International Congress on Sarcopenia, Cachexia and Wasting Disorders. This work highlights the relevance of specific circulating biomarkers—identified within the FRASNET study—in detecting malnutrition among older adults, and underscores the potential clinical utility of molecular profiling in geriatric risk stratification. In May, efforts were dedicated to writing a full scientific manuscript entitled “Mitokine Signatures of Aging: GDF-15 and FGF21 Predict Frailty, Sarcopenia, and Malnutrition in the FRASNET Study”, submitted to Mechanisms of Ageing and Development. The paper reports novel associations between mitokines and common geriatric syndromes, strengthening the evidence base for their role as early biomarkers of biological aging and functional decline. In June 2025 results from this line of research were also presented at the national level in June, during the 13th Congresso I.S.Mu.L.T., held in Milan. The oral presentation, titled “Biomarkers per la sarcopenia: come prevenire il declino della massa e della funzione muscolare”, was aimed at a clinical and scientific audience, with the goal of translating biomarker research into practical insights for preventing muscle loss and functional impairment in older adults.
Publications
Dissemination