Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors
Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors
ABSTRACT PurposeSurvival rates of Childhood Cancer Patients have improved tremendously over the past four decades. However, cancer treatments are associated with an increased risk of developing an anticipated onset of chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in Childhood Cancer Survivors (CCS). Patients and MethodsBiochemical, proteomic and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, comparing the results with those obtained on MNCs of 154 healthy subjects. ResultsData demonstrate that CCS-MNCs show: i) inefficient oxidative phosphorylation associated with low energy status and a metabolic switch to lactate fermentation compared with age-matched normal controls; ii) increment of lipid peroxidation due to an unbalance among the oxidative stress production and the activation of the antioxidant defenses; (iii) significantly lower expression of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-α, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. The application of a mathematical model based on biochemical parameters predicts that CCS have a biological age significantly increased by decades compared to the chronological age. Overall, the results show that the impact of chemo/chemoradiotherapy on mitochondria efficiency in 196 CCS was rather homogeneous, irrespective of cancer type, treatment protocols, and time elapsed from the end of the curative period. ConclusionsOur study identifies some biochemical and molecular alterations possibly contributing to the pathophysiology of anticipated aging and metabolic deficiency described in CCS. These results may be useful in identifying approaches to restore the mitochondrial function, slowing down the aging and the associated pathological conditions in CCS.
Haupt Riccardo、Ravera Silvia、Muraca Monica、Bartolucci Martina、Vigliarolo Tiziana、Morandi Fabio、Dagnino Monica、Biasin Eleonora、Podest¨¤ Marina、Frassoni Francesco、Marimpietri Danilo、Bruno Silvia、Sabatini Federica、Zecca Marco、Fagioli Franca、Cilloni Daniela、Petretto Andrea
Epidemiology and Biostatistics Unit and DOPO Clinic, IRCCS Istituto Giannina GasliniStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini||Department of Experimental Medicine, University of GenoaEpidemiology and Biostatistics Unit and DOPO Clinic, IRCCS Istituto Giannina GasliniCore Facilities-Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina GasliniStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina GasliniStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina GasliniStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina GasliniDepartment of Pediatric Onco-Haematology, Regina Margherita Children?ˉs Hospital, University of Turin - TurinStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina GasliniStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini||Department of Clinical and Biological Sciences, School of Medicine, University of Turin||Department of Mathematics (DIMA), University of GenoaStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina GasliniDepartment of Experimental Medicine, University of GenoaStem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina GasliniPediatric Hematology OncologyDepartment of Pediatric Onco-Haematology, Regina Margherita Children?ˉs Hospital, University of Turin - TurinDepartment of Clinical and Biological Sciences, School of Medicine, University of TurinCore Facilities-Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini
医学研究方法基础医学分子生物学
Haupt Riccardo,Ravera Silvia,Muraca Monica,Bartolucci Martina,Vigliarolo Tiziana,Morandi Fabio,Dagnino Monica,Biasin Eleonora,Podest¨¤ Marina,Frassoni Francesco,Marimpietri Danilo,Bruno Silvia,Sabatini Federica,Zecca Marco,Fagioli Franca,Cilloni Daniela,Petretto Andrea.Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2021.04.01.438017.点此复制
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