The biological age linked to oxidative stress modifies breast cancer aggressiveness

Abstract

The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging.

Extraction Optimization and Effects of Extraction Methods on the Chemical Structures and Antioxidant Activities of Polysaccharides from Snow Chrysanthemum (Coreopsis Tinctoria)

“…Elevated level of ROS results in the generation of free radicals which can cause deleterious effects on protein, lipids, and deoxyribonucleic acid (DNA) [2]. Free radicals-induced oxidative stress plays an important role in the pathophysiology of various disease conditions, such as neurodegenerative disorders, cancer, cardiovascular, inflammatory diseases, and aging [3,4]. Antioxidants can alleviate the oxidative stress, which is beneficial for human health.…”

Evolutionary Origins of Metabolic Reprogramming in Cancer

“…It is likely that genetic variants related to metabolism and the changes they induce in immune activity are related to more effective wound repair, but in later stages in life also bestow greater tumor susceptibility or more efficient tumor growth. For example, Zbp-1 , essential for the response to viruses, has been related to a higher susceptibility to breast cancer in a mouse model [ 110 ].…”

“…Consequently, the possibility cannot be ruled out that these wound-healing- and cancer-related intermediate phenotypes are local and systemic. For example, changes in liver signaling pathways associated with tumor evolution [ 7 , 206 ] and a series of systemic metabolites related to it [ 7 , 110 , 206 ] have been described.…”

RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway

“…The incidence and mortality of BC are increasing each year [ 2 ]. The incidence of BC rises with age until menopause, and BC is more aggressive in younger females [ 3 ]. Despite the therapeutic strategies for BC have been improved greatly, patients still suffer from some adverse effects such as poor outcomes and drug-resistance [ 4 ].…”