Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration

Aging is a prominent risk factor for neurodegenerative disorders (NDDs); however, the molecular mechanisms rendering the aged brain particularly susceptible to neurodegeneration remain unclear. Here, we aim to determine the link between physiological aging and NDDs by exploring protein turnover using metabolic labeling and quantitative pulse-SILAC proteomics. By comparing protein lifetimes between physiologically aged and young adult mice, we found that in aged brains protein lifetimes are increased by ~20% and that aging affects distinct pathways linked to NDDs. Specifically, a set of neuroprotective proteins are longer-lived in aged brains, while some mitochondrial proteins linked to neurodegeneration are shorter-lived. Strikingly, we observed a previously unknown alteration in proteostasis that correlates to parsimonious turnover of proteins with high biosynthetic costs, revealing an overall metabolic adaptation that preludes neurodegeneration. Our findings suggest that future therapeutic paradigms, aimed at addressing these metabolic adaptations, might be able to delay NDD onset

Realistic Earth escape strategies for solar sailing

With growing interest in solar sailing comes the requirement to provide a basis for future detailed planetary escape mission analysis by drawing together prior work, clarifying and explaining previously anomalies. Previously unexplained seasonal variations in sail escape times from Earth orbit are explained analytically and corroborated within a numerical trajectory model. Blended-sail control algorithms, explicitly independent of time, which providenear-optimal escape trajectories and maintain a safe minimum altitude and which are suitable as a potential autonomous onboard controller, are then presented. These algorithms are investigated from a range of initial conditions and are shown to maintain the optimality previously demonstrated by the use of a single-energy gain control law but without the risk of planetary collision. Finally, it is shown that the minimum sail characteristic acceleration required for escape from a polar orbit without traversing the Earth shadow cone increases exponentially as initial altitude is decreased