Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization

Abstract

While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.

Keywords: DNA damage; Mars mission; longevity; radioresistance; space exploration.

Figure 1. Major sources of space radiation

The space radiation comes from three major sources including galactic cosmic rays, sun radiation and Van Allen radiation belts of the Earth.

Figure 2. Comparative diagram on DNA damage induced by Low- and High-LET radiation

HZE particles, also called “densely ionizing radiation” typically deposit a large amount of their energy along linear tracks referred to as cores, while the remaining energy is deposited radially and uniformly by secondary electrons (i.e. Delta-rays). In contrast, low-LET deposit their energy uniformly and are often referred as “sparsely ionizing radiation”.

Figure 3. Ways to reduce health risks from space radiation during deep space travels

Multiple approaches from medical selection of radioresistant individuals to gene therapy may be proposed.

Figure 4. Common molecular mechanisms involved in the response to the effects of space radiation and the geroprotectors affecting the regulation of those

Space radiation induces cellular response through the direct DNA damage, ROS accumulation and non-targeted effects. These types of damage provoke distinct signalling mechanisms that may be regulated by the small molecules.

Figure 5. Conceptual diagram of a genetic system for elimination of radiation-damaged cells and subsequent inducible stem cell activation and regeneration of affected tissues

A variety of specific genetic elements that could be used in such system have previously been described (see text for further detail).