What to expect after a year in space: Space is the final frontier for understanding how extreme environments affect human physiology. Following twin astronauts, one of which spent a year-long mission on the International Space Station, Garrett-Bakelman et al. examined molecular and physiological traits that may be affected by time in space (see the Perspective by Löbrich and Jeggo). Sequencing the components of whole blood revealed that the length of telomeres, which is important to maintain in dividing cells and may be related to human aging, changed substantially during space flight and again upon return to Earth. Coupled with changes in DNA methylation in immune cells and cardiovascular and cognitive effects, this study provides a basis to assess the hazards of long-term space habitation. Science , this issue p. eaau8650 ; see also p. 127

Background: Muscle inactivity and low energy intake commonly occur in persons with acute or chronic disease, in astronauts during space flight, and during aging. Objective: We used a crossover design to investigate the effects of the interactions of inactivity and calorie restriction on whole-body composition and protein kinetic regulation in 9 healthy volunteers. Design: Lean body mass (LBM) was measured by using dual-energy X-ray absorptionmetry before and at the end of 14-d periods of bed rest (B) and controlled ambulation (A) in patients receiving eucaloric (E) or hypocaloric (H) (≈80% of total energy expenditure) diets. Whole-body leucine kinetics were determined at the end of the 4 study periods by using a standard stable-isotope technique in the postabsorptive state and during a 3-h infusion of a 0.13 g · kg LBM⁻¹ · h⁻¹ amino acid mixture. Results: In the postabsorptive state, we found a significant (P = 0.04) bed rest × hypocaloric diet interaction for the rate of leucine oxidation, an index of net protein catabolism (A+E: 0.23 ± 0.01; B+E: 25 ± 0.01; A+H: 0.23 ± 0.01; B+H: 0.28 ± 0.01 μmol · min⁻¹ · kg LBM⁻¹). Bed rest significantly (P < 0.01) decreased amino acid–mediated stimulation of nonoxidative leucine disappearance, an index of protein synthesis (A+E: 35 ± 2%; B+E: 30 ± 2%; A+H: 41 ± 3%; B+H: 32 ± 2%). B+H decreased LBM by 1.10 ± 0.1 kg, which is significantly (P < 0.01) greater than the decrease seen with A+E, A+H, or B+E. Conclusion: Calorie restriction enhanced the catabolic response to inactivity by combining greater protein catabolism in the postabsorptive state with an impaired postprandial anabolic utilization of free amino acids.