Radiation Hormesis Studied in Flies

Hormesis is the process whereby a little damage leads to a lasting increase in the activities of cellular repair mechanisms, with the outcome of a net gain in systems integrity and function. Hormesis is involved in a majority of the interventions shown to modestly slow aging in at least some short-lived species, such as low level radiation treatment. Here researchers add to the data on radiation hormesis and life span in flies, showing life extension of 3% to 7% that varied by gender but, perhaps surprisingly, not by dose:

Although there are many common mechanisms of response of organism and cell to irradiation and other stresses (thermal, oxidative, etc.), their principal difference is a significant role of DNA damage on the biological effects of ionizing radiation. However, these differences are attributed mostly to high dose rates. In the case of low dose radiation, direct effects of irradiation such as clustered DNA damage and DNA double strand breaks are minimal, whereas indirect DNA damages caused by the induction of reactive oxygen species become the primary result. In high doses, adverse effects accumulate in the tissues in a deterministic manner that depends linearly on the dose, but in low doses the effects are stochastic, non-linear on the dose, and depend mainly on the efficiency of the stress response's protective mechanisms.

Therefore, low doses of radiation can be regarded as moderate stress, which is known to induce hormesis. Indeed, in our previous work, and in the work of other authors it has been revealed, that relatively low dose exposure (20-75 cGy) of fruit flies on immature preimaginal stages in some cases has long-term effects that lead to an increased life span and resistance to other stresses, such as hyperthermia. It is known that preimaginal stages of Drosophila have comparable radiosensitivity to mammals. At the same time, adult individuals, due to the postmitotic state of most tissues, are about 100 times more radioresistant. Other researchers have revealed that irradiation of Drosophila individuals in the imago stage in doses from 0.1 to 400 Gy causes a statistically significant effect on lifespan and gene expression only if the dose is higher than 100 Gy. At the same time, in our recent work on comparing the effects of irradiation in the adult Drosophila male and female at the 20 cGy dose rate, we observed some differentially expressed genes.

Although some changes in life extensity in males were identified (the effect of hormesis after the exposure to 5, 10 and 40 cGy) as well as in females (the effect of hormesis after the exposure to 5 and 40 cGy), they were not caused by the organism "physiological" changes. This means that the observed changes in life expectancy are not related to the changes of organism physiological functions after the exposure to low doses of ionizing radiation. The identified changes in gene expression are not dose-dependent, there is not any proportionality between dose and its impact on expression. These results reflect nonlinear effects of low dose radiation and sex-specific radio-resistance of the postmitotic cell state of Drosophila melanogaster imago.

Link: http://dx.doi.org/10.1371/journal.pone.0133840


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