Table 2.

Specific hallmarks of aging and evidence in cancer survivors

Hallmark of Aging	Evidence in cancer survivors
Genomic instability	Chromosomal abnormalities are documented in Hodgkin Lymphoma survivors [59–63]
Telomere attrition	Relative telomere shortening is documented in survivors of childhood leukemia, high risk neuroblastoma and is associated with chronic disease in survivors of childhood cancer [31, 64, 65]
Epigenetic alterations	DNA methylation patterns differ between survivors of Hodgkin Lymphoma and their monozygotic twins, are altered in T-cells and associated with over-activated cytokine signaling pathways of survivors of childhood cancer treated with hematopoietic stem cell transplantation, and are associated with obesity in survivors of childhood onset acute lymphoblastic leukemia. [66–68]
Loss of proteostasis	Differences in mitochondrial protein content are documented in survivors of childhood acute lymphoblastic leukemia when compared to healthy controls.[69]
Dysregulated nutrient sensing	Growth hormone deficiency is common in cancer survivors whose hypothalamic-pituitary axis is exposed to radiation.[70, 71] Downregulation of metabolism in cancer survivors is thought to be a protective mechanism to spare cellular damage.[47]
Mitochondrial dysfunction	Differential expression of genes related to mitochondrial function are reported in breast cancer survivors with peripheral neuropathy and cardiomyopathy.[75, 112]Children treated with anthracyclines dexrazoxane, a cardio protectant) have higher mitochondrial content per cell than those who had anthracycline exposure with no dexrazoxane.[76]
Cellular senescence	Markers of cellular senescence and associated inflammatory cytokines are evident in breast cancer survivors, survivors of childhood acute lymphoblastic leukemia, and those treated with hematopoietic stem cell transplant.[77–80]
Altered intercellular communication	Increased tumor cell levels of advanced glycation end products (AGEs), reactive metabolites produced during normal metabolism, are documented among women with estrogen receptor positive (ER+) breast cancer when compared to those with ER- breast cancer.[82]