de Lisio, Laura (2026) Circulating biomarkers of aging: focus on frailty and survival. [Tesi di dottorato]

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Abstract

Aging is a complex and heterogeneous process characterized by a progressive decline in physiological reserves, increased vulnerability to adverse outcomes and it is strongly linked to functional impairment, disability, and mortality. Understanding the biological mechanisms that correlate with frailty can help early identification of high-risk patients and informs personalized interventions. In our study, a total of 248 older adults were enrolled and underwent a Comprehensive Geriatric Assessment; frailty was quantified using a Frailty Index, based on Rockwood's deficit accumulation model. Blood samples were collected, and plasma levels FGF21, GDF15, sRAGE, BDNF, and NfL were measured with EllaTM Automated Immunoassay. The relationships between circulating biomarkers and frailty were analyzed using multivariable regression models adjusted for age and sex. In addition, survival analyses were performed to investigate the association between frailty, biomarker, and mortality. The analysis showed that higher levels of FGF21, GDF15, and NfL were associated with increased frailty, while only NfL and sRAGE remained independently associated with frailty even after adjustment. The survival analysis showed a significantly statistical correlation between elevated levels of GDF15 and sRAGE and mortality. Overall, these results highlight a close relationship between frailty, biological pathways related to inflammation, metabolic stress, and neuronal damage, and adverse clinical outcomes in older adults. The integration of circulating biomarkers with multidimensional clinical assessment may contribute to a more accurate characterization of frailty and help identify individuals at higher risk within aging populations.

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