Highlights d Multi-omics analysis and techniques with NASA's GeneLab platform d The largest cohort of astronaut data to date utilized for analysis d Mitochondrial dysregulation driving spaceflight health risks d NASA Twin Study data validates mitochondrial dysfunction during space missions

The circadian clock is a cellular machine composed of proteins with regulated expression that gives rise to circadian rhythms. Two main new concepts have arisen from recent research in the field in the last few years: (i) at least three to five key genes are involved in maintaining the basic circadian cellular rhythms, and (ii) their expression is fairly ubiquitous, extending beyond the traditionally considered pacemaker in mammals, the suprachiasmatic nucleus. We have demonstrated the expression of two circadian clock genes, clock and period1, in human skin cells. Reverse transcriptase polymerase chain reaction revealed the presence of clock and period1 mRNA in cultured human keratinocytes, melanocytes, and dermal fibroblasts, as well as in the human keratinocyte cell line HaCaT and the human melanoma line A375. In addition, antibodies to these two proteins produced immuno-positive staining in these cell types. Our investigations demonstrate for the first time that skin cells express circadian clock proteins constitutively although regulation of their expression and activity has not been elucidated. These proteins may have a role in cutaneous and/or systemic circadian biology and the skin and skin cells may provide an attractive model for the study of circadian rhythms.

PurposeTo compare ocular outcomes in healthy subjects undergoing 14- and/or 70-day head-down-tilt (HDT) bed rest (BR).MethodsParticipants were selected by using NASA standard screening procedures. Standardized NASA BR conditions were implemented. Subjects maintained a 6° HDT position for 14 and/or 70 consecutive days. Weekly ophthalmologic examinations were performed in the sitting (pre/post-BR only) and HDT positions. Mixed-effects linear models compared pre- and post-HDT BR observations between 14- and 70-day HDT BR in best-corrected visual acuity, spherical equivalent, intraocular pressure (IOP), Spectralis OCT retinal nerve fiber layer thickness, peripapillary and macular retinal thicknesses.ResultsSixteen and six subjects completed the 14- and 70-day HDT BR studies, respectively. The magnitude of HDT BR–induced changes was not significantly different between the two studies for all outcomes, except the superior (mean pre/post difference of 14- vs. 70-day HDT BR: +4.69 μm versus +11.50 μm), nasal (+4.63 μm versus +11.46 μm), and inferior (+4.34 μm versus +10.08 μm) peripapillary retinal thickness. A +1.42 mm Hg and a +1.79 mm Hg iCare IOP increase from baseline occurred during 14- and 70-day HDT BR, respectively. Modified Amsler grid, red dot test, confrontational visual field, color vision, and stereoscopic fundus photography were unremarkable.ConclusionsSeventy-day HDT BR induced greater peripapillary retinal thickening than 14-day HDT BR, suggesting that time may affect the amount of optic disc swelling. Spectralis OCT detected retinal nerve fiber layer thickening post BR, without clinical signs of optic disc edema. A small IOP increase during BR subsided post HDT BR. Such changes may have resulted from BR-induced cephalad fluids shift. The HDT BR duration may be critical for replicating microgravity-related ophthalmologic changes observed in astronauts on ≥6-month spaceflights.

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