Potential role of senescence in radiation-induced damage of the aged skeleton

Human aging-related changes are exacerbated in cases of disease and cancer, and conversely aging is a catalyst for the occurrence of disease and multimorbidity. For example, old age is the most significant risk factor for cancer and among people who suffer from cancer, >60% are above the age of 65. Oxidative stress and DNA damage, leading to genomic instability and telomere dysfunction, are prevalent in aging and radiation-induced damage and are major cellular events that lead to senescence. Human exposures from nuclear fallout, cosmic radiation and clinical radiotherapy (RT) are some common sources of irradiation that affect bone tissue. RT has been used to treat malignant tumors for over a century, but the effects of radiation damage on tumor-adjacent normal tissue has largely been overlooked. There is an increase in the percent survivorship among patients post-RT, and it is in older survivors where the deleterious synergy between aging and radiation exposure conspires to promote tissue deterioration and dysfunction which then negatively impacts their quality of life. Thus, an aging skeleton is already pre-disposed to architectural deterioration, which is further worsened by radiation-induced bone damage. Effects of senescence and the senescence associated secretory phenotype (SASP) have been implicated in age-associated bone loss, but their roles in radiation-associated bone damage are still elusive. RT is used in treatment for a variety of cancers and in different anatomical locations, the sequelae of which include long-term morbidity and lifelong discomfort. Therefore, consideration of the growing evidence that implicates the role of senescence in radiation-induced bone damage argues in favor of exploiting current senotherapeutic approaches as a possible prevention or treatment.