Spontaneous p53 activation in middle-aged C57BL/6 mice mitigates the lifespan-extending adaptive response induced by low-dose ionizing radiation.

Abstract

Abstract Understanding the biological effects of low-dose (< 100 mGy) ionizing radiation (LDIR) is technically challenging. We aimed to understand age-dependent LDIR effects using adaptive response experiments in young (7–12 weeks) and middle-aged (40–62 weeks) C57BL/6 mice. Compared with 3 Gy irradiation, 0.02 Gy pre-IR followed by 3 Gy had life-prolonging effects on young mice but not middle-aged mice. 53BP1 repair foci in the small intestines of young mice, but not middle-aged mice, induced by 3 Gy were suppressed at 4 h by 0.02 Gy pre-IR. Consistently, splenic apoptosis and p53 activity were decreased by 0.02 Gy + 3 Gy compared with 3 Gy in young mice but not middle-aged mice. Interestingly, p53 activations in middle-aged mice were spontaneously increased by approximately 4.5-fold compared to that in young mice. Such chronic p53 activation in middle-aged mice may mask the adaptive responses induced by LDIR, which are essential for lifespan extension after high-dose IR.