Biological Aspects of Inflamm-Aging in Childhood Cancer Survivors

Anti-cancer treatments improve survival in children with cancer. A total of 80% of children treated for childhood cancer achieve 5-year survival, becoming long-term survivors. However, they undergo several chronic late effects related to treatments. In childhood cancer survivors a chronic low-grade inflammation, known as inflamm-aging, is responsible for frailty, a condition characterized by vital organ failure and by premature aging processes. Inflamm-aging is closely related to chemotherapy and radiotherapy, which induce inflammation, accumulation of senescent cells, DNA mutations, and the production of reactive oxygen species. All these conditions are responsible for the onset of secondary diseases, such as osteoporosis, cardiovascular diseases, obesity, and infertility. Considering that the pathobiology of frailty among childhood cancer survivors is still unknown, investigations are needed to better understand frailty's biological and molecular processes and to identify inflamm-aging key biomarkers in order to facilitate the screening of comorbidities and to clarify whether treatments, normally used to modulate inflamm-aging, may be beneficial. This review offers an overview of the possible biological mechanisms involved in the development of inflamm-aging, focusing our attention on immune system alteration, oxidative stress, cellular senescence, and therapeutic strategies.