Editors' ChoiceCancer

Some things get better with age

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Science Translational Medicine  11 Mar 2015:
Vol. 7, Issue 278, pp. 278ec39
DOI: 10.1126/scitranslmed.aaa9863

Genetics, diet, and environmental factors all influence cancer susceptibility, but advancing age usually dominates the risk profile. With rare exceptions, most common cancers occur in older adults. In the United States, among individuals age 65 years and older, cancer is the second leading cause of death after heart disease. In accord with these trends, clinical and radiographic screening for cancer generally does not start until individuals have reached their 40s or 50s.

Why older adults are more prone to cancer remains a complex and largely unanswered question. The trend may reflect cumulative exposure to risk factors, the burden of spontaneous mutations, the number of cell divisions in stem cells, or a delay between precancerous lesions and invasive malignancy. Some studies have implicated age-associated changes in epigenetic alterations, telomere attrition, mitochondrial dysfunction, or genomic instability.

Beheshti et al. have supplemented these observations by focusing not on cancer incidence but rather on cancer progression. In a syngeneic model, they injected Lewis Lung Cancer cells into groups of C57BL/6 male mice aged 68 days (young adult), 143 days (adolescent), 551 days (middle-aged), and 736 days (old). Tumors were evaluated for genome-wide expression profiling and growth dynamics. Among the 2596 genes evaluated in tumor samples, 571 common genes showed age-dependent changes (304 up-regulated, 267 down-regulated). Older animals had dysregulated angiogenesis, metabolism, and apoptosis. TGFβ1, a central player in these processes, was consistently down-regulated in older mice. Although older mice had higher rates of genomic instability, tumors grew more slowly in the oldest cohort.

The results present a mixed but hopeful message for older adults. Higher rates of genomic instability could account for greater cancer incidence. But once cancer develops, host-related factors may render it less aggressive. These preclinical findings are consistent with clinical observations that in younger patients, common cancers such as breast, colorectal, and lung have worse outcomes.

A. Beheshti et al., Host age is a systematic regulator of gene expression impacting cancer progression. Cancer Res. 10.1158/0008-5472.CAN-14-1053 (2015). [Abstract]

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