Antioxidants · Nov 10, 2026
Biomarkers of Premature Biological Aging in Hodgkin Lymphoma Survivors: Advanced Glycation End Products, Oxidative Stress, Inflammation and Cellular Senescence
By Aimaretti E, Rubeo C, Levis M et al.
Childhood, adolescent, and young adult cancer survivors (CAYACS) are at increased risk of late morbidity, potentially reflecting premature biological aging. Cellular senescence, oxidative stress, and chronic inflammation may contribute via interconnected pathways, including signaling mediated by advanced glycation end products (AGEs) and their receptor, RAGE. This study investigated biomarkers related to these pathways in CAYACS-treated Hodgkin lymphoma (HL) patients, comparing their biological profile with that of age-matched (Controls 1) and older (aged 50–65) healthy controls (Controls 2). HL survivors exhibited accumulation of AGEs, higher expression of their receptor RAGE and lower circulating levels of soluble RAGE compared to age-matched Controls 1. A similar profile of AGE-RAGE signaling was observed in Controls 2. HL survivors and Controls 2 showed an altered oxidative status. Moreover, HL survivors reported higher plasma levels of IL-6 than age-matched controls. Furthermore, HL survivors and Controls 2 showed alterations in autophagy and mitophagy. Finally, CAYACS had higher plasma MMP9 levels and higher p16 mRNA levels than age-matched Controls 1. Data show that CAYACS exhibit a biological profile consistent with premature cellular senescence, with several features resembling those observed in older healthy individuals. Alterations in AGE-RAGE signaling, oxidative stress-related pathways, and chronic inflammation may lead to the onset of this phenotype. Further longitudinal studies are needed to clarify the potential role of these biological alterations in the development of long-term treatment-related complications.