Age and space irradiation modulate tumor progression: implications for carcinogenesis risk

Area of Science:

• Oncology
• Radiation Biology
• Gerontology

Background:

• Cancer incidence typically rises with age due to accumulated DNA damage.
• However, cancer incidence decelerates and can decrease in older age groups.
• The role of host capacity in tumor progression and radiation effects is crucial for astronaut cancer risk assessment.

Purpose of the Study:

• Investigate if reduced host capacity in older mice explains decelerated tumor progression.
• Determine if high atomic number (Z), high energy (E) radiation differentially affects tumor progression in young versus middle-aged mice.
• Identify molecular mechanisms underlying radiation's impact on age-dependent tumor dynamics.

Main Methods:

• Injected Lewis lung carcinoma (LLC) cells into young (143 days) and middle-aged (551 days) syngeneic mice.
• Exposed mice to whole-body iron-56 ((56)Fe) irradiation (1 GeV/amu).
• Analyzed tumor progression, growth rates, and global gene expression.

Main Results:

• Unirradiated middle-aged mice exhibited significantly inhibited tumor progression compared to young mice.
• (56)Fe irradiation suppressed tumor progression in both age groups, with a greater effect in younger mice.
• Irradiation's effect on young mice approximated the transition to middle-aged tumor progression, suggesting radiation mimics aging.

Conclusions:

• Middle-aged hosts have a diminished capacity to support tumor progression.
• (56)Fe irradiation modulates tumor progression similarly to aging.
• FASN, AKT1, and the CXCL12/CXCR4 complex are key molecular factors in age-dependent radiation effects on tumors.