Normal Tissue Development, Homeostasis, Senescence, and the Sensitivity to Radiation Injury Across the Age Spectrum

Late effects in normal tissues following radiotherapy vary across the age spectrum. It seems that sensitivity to radiation injury is a function of the developmental dynamics and status of the organ, its regenerative potential, and ultimately the extent to which it has begun to senesce. For instance, organ maturational processes in children can be impaired or even disabled by radiation therapy, leading to a spectrum of effects that differ from those in adults, in which the capacity and means for tissues to repair damage are the predominant predictor for chronic injury. Thus, radiation-induced impairment of growth and maturation is unique to children, whereas organ damage, with tissue-specific dysfunction in repair processes, is common to both children and adults. Finally, the susceptibility to late effects in the elderly seems to involve not only a decline in their ability to repair damage, but also cell attrition, all intertwined with effects of comorbid illness that are frequent in this age group. The challenge for clinicians is to understand these differences in the sensitivity to radiation damage with respect to age to formulate a basis for modulating therapy that can rationally minimize late effects and maximize a survivor's quality of life.