Revisiting the Walburg hypothesis that radiation affects only tumor deaths but not non-tumor deaths in mice.

Abstract

Starting in the 1950s or earlier, irradiation was found to shorten lifespans in mice, which raised the possibility that radiation science might contribute to an understanding of the nature of aging. However, in 1975, Walburg published a review paper to express his hypothesis that radiation exposure increases the risk of tumor deaths but not for non-tumor deaths. Subsequently, it became a mainstream belief that irradiation induces oncogenic mutations and thereby increases the risk of cancer and thus life shortening. However, we now think that the Walburg's hypothesis is not tenable as it did not include contradictory studies that were available before 1975, and additional contradictory papers were published after 1975; namely, all irradiated individuals are affected. If we accept the notion that irradiation shortens the lifespan of all individuals regardless of the cause of death, it suggests that irradiation may accelerate general aging. Based on these considerations and other available evidence in the field, the mutation induction theory appears untenable as the sole mechanism in radiation carcinogenesis. Under such conditions, the old hypothesis that radiation induces accelerated aging should be revived. Current knowledge in the field of natural aging supports the hypothesis that radiation causes DNA breaks, most of which are correctly repaired, but not at the chromatin level (chromatin fatigue) which leads to accelerated aging. The critical difference from the traditional mutagenesis model is that no stem cell mutagenesis is necessary to consider.