Circadian regulation in aging: Implications for spaceflight and life on earth.

Alterations in the circadian system are characteristic of aging on Earth. With the decline in physiological processes due to aging, several health concerns including vision loss, cardiovascular disorders, cognitive impairments, and muscle mass loss arise in elderly populations. Similar health risks are reported as "red flag" risks among astronauts during and after a long-term Space exploration journey. However, little is known about the common molecular alterations underlying terrestrial aging and space-related aging in astronauts, and controversial conclusions have been recently reported. In light of the regulatory role of the circadian clock in the maintenance of human health, we review here the overlapping role of the circadian clock both on aging on Earth and spaceflight with a focus on the four most affected systems: visual, cardiovascular, central nervous, and musculoskeletal systems. In this review, we briefly introduce the regulatory role of the circadian clock in specific cellular processes followed by alterations in those processes due to aging. We next summarize the known molecular alterations associated with spaceflight, highlighting involved clock-regulated genes in space flown Drosophila, nematodes, small mammals, and astronauts. Finally, we discuss common genes that are altered in terms of their expression due to aging on Earth and spaceflight. Altogether, the data elaborated in this review strengthen our hypothesis regarding the timely need to include circadian dysregulation as an emerging hallmark of aging on Earth and beyond.