Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors

Silvia Ravera, Tiziana Vigliarolo, Silvia Bruno, Fabio Morandi, Danilo Marimpietri, Federica Sabatini, Monica Dagnino, Andrea Petretto, Martina Bartolucci, Monica Muraca, Eleonora Biasin, Riccardo Haupt, Marco Zecca, Franca Fagioli, Daniela Cilloni, Marina Podestà, Francesco Frassoni

Research output: Contribution to journalArticlepeer-review


Survival rates of childhood cancer patients have improved over the past four decades, although cancer treatments increase the risk of developing chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in childhood cancer survivors (CCS). Biochemical, proteomic, and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, the results being compared with those obtained on MNCs of 154 healthy subjects. CCS-MNCs showed inefficient oxidative phosphorylation associated with low energy status, and increased lipid peroxidation and lactate fermentation compared with age-matched normal controls. According to a mathematical model based on biochemical parameters, CCS-MNCs showed significantly higher metabolic ages than their real ages. The dysfunctional metabolism of CCS-MNCs is associated with lower expression levels of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-alpha, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. In conclusion, our study identified some biochemical and molecular alterations possibly contributing to the pathophysiology of aging and metabolic deficiencies in CCS. These results identify new targets for pharmacological interventions to restore mitochondrial function, slowing down the aging-associated pathologies in CCS.

Original languageEnglish
Issue number20
Publication statusPublished - Oct 18 2021


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