Wallis, G. | Search bioRxiv

bioRxiv2019

Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial

NAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

clinical trials↗

bioRxiv2019

Rapid recalibration of temporal order judgements: Response bias accounts for contradictory results

Recent findings indicate that timing perception is systematically changed after only a single presentation of temporal asynchrony. This effect is known as rapid recalibration. In the synchrony judgement task, similar timing relationships in consecutive trials seem more synchronous (positive rapid recalibration; Van der Burg et al., 2013, 2015). Interestingly, the direction of this effect is reversed for temporal order judgements (negative rapid recalibration; Roseboom, 2019). We aimed to determine whether negative rapid recalibration of temporal order judgements (TOJs) reflects genuine rapid temporal recalibration, or a choice-repetition bias unrelated to timing perception. In our first experiment we found no evidence of rapid recalibration of TOJs, but positive rapid recalibration of associated confidence. This suggests that timing perception had rapidly recalibrated, but that this was undetectable in TOJs, plausibly because the positive recalibration effect was obfuscated by a large negative bias effect. In our second experiment, we dissociated participants previous TOJ from the most recently presented timing relationship, mitigating the choice-repetition bias effect, and found evidence of positive rapid recalibration of TOJs. We therefore conclude that timing perception is rapidly recalibrated positively for both synchrony and temporal order judgements. It remains unclear whether rapid recalibration occurs at the level of sensory processing, leading to similar effects in all subsequent judgements, or reflects a generalised decision-making strategy.

neuroscience↗