Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD + can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD + precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD + metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD + boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

TIME-seq reduces time and cost of DNA methylation measurement for epigenetic clock construction.

Epigenetic 'clocks' based on DNA methylation have emerged as the most robust and widely used aging biomarkers, but conventional methods for applying them are expensive and laborious. Here we develop tagmentation-based indexing for methylation sequencing (TIME-seq), a highly multiplexed and scalable method for low-cost epigenetic clocks. Using TIME-seq, we applied multi-tissue and tissue-specific epigenetic clocks in over 1,800 mouse DNA samples from eight tissue and cell types. We show that TIME-seq clocks are accurate and robust, enriched for polycomb repressive complex 2-regulated loci, and benchmark favorably against conventional methods despite being up to 100-fold less expensive. Using dietary treatments and gene therapy, we find that TIME-seq clocks reflect diverse interventions in multiple tissues. Finally, we develop an economical human blood clock (R > 0.96, median error = 3.39 years) in 1,056 demographically representative individuals. These methods will enable more efficient epigenetic clock measurement in larger-scale human and animal studies.

Is barium esophagram enough? Comparison of esophageal motility found on barium esophagram to high resolution manometry.

BACKGROUND: The aim of the study is to determine if barium esophagram (BE) alone is sufficient to diagnose esophageal dysmotility when compared to the gold standard, high-resolution manometry (HRM). METHODS: This is a retrospective review of patients that underwent laparoscopic fundoplication by two surgeons at a single institution from 10/1/2015-6/29/2019. Patients with large paraesophageal hernias and patients without both BE and HRM were excluded. RESULTS: Forty-six patients met the inclusion criteria. BE was found to be concordant with HRM for esophageal motility in only 21 patients (46%). Setting HRM as the gold standard, BE had a sensitivity of 14% (95% CI: 5%-35%), specificity of 72% (95% CI: 52%-86%), PPV of 30% (95% CI: 11%-60%), and NPV of 50% (95% CI: 35%-66%). The accuracy was 46%, while a McNemar test showed p = 0.028. CONCLUSION: Traditional BE should not be used in place of HRM for assessing pre-operative motility in patients undergoing anti-reflux surgery.

When fiberoptic intubation fails in patients with unstable craniovertebral junctions.

Fiberoptic intubation (FOI) is generally regarded as the preferred method to achieve endotracheal intubation in patients with cervical spine instability. When performed electively, FOI has a very high level of success. Nevertheless, rarely, FOI may fail. Recently, using the fiberoptic scope to obtain a view of the glottis, with the endotracheal tube being inserted independently, guided by the fiberoptic view has been described. In this report, we describe our experience with a variation of this technique in both adults and children with occipito-cervical instabilities in whom FOI failed.