Conway, R. | Search bioRxiv

bioRxiv2024

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.

pharmacology and toxicology↗

bioRxiv2022

Aspects of flow variability and spatial context predict temporal beta diversity in river metacommunities

O_LIRiver catchments are dynamic networks that contain multiple levels of spatial and temporal complexity. Benthic macroinvertebrates are key indicator taxa throughout catchments and beta diversity has been used as a metric to explore determinants of community composition at the catchment scale. Commonly explored drivers of beta diversity include environmental and spatial variables such as flow, temperature, and spatial distance. While factors influencing spatial beta diversity have been explored, factors explaining temporal beta diversity have been understudied. Temporal beta diversity is predicted to also be important since community assembly mechanisms are not stable over time, and more studies are needed to determine which factors most strongly determine temporal beta diversity patterns. C_LIO_LIWe investigated the effects of local environmental variables, flow variability, and spatial context on temporal beta-diversity using a large, publicly available biomonitoring dataset from river networks in California. Data included benthic macroinvertebrate community composition and environmental data from multiple locations and years, allowing us to explore temporal changes in these communities as a function of site-specific environmental and spatial factors. Associated gage data were used to calculate hydrograph metrics and contextualize the flow regime at each location over long timescales. We then used beta regression to model the relationship between benthic macroinvertebrate temporal beta-diversity, environmental variables, flow regimes, and spatial network context. C_LIO_LIFlow and spatial catchment-related predictors were the strongest predictors of temporal beta diversity, while changes in environmental variables were much weaker. Channel slope, drainage density, and upstream catchment area were the most significant spatial factors. Channel slope showed a negative relationship with temporal beta diversity, while drainage density and upstream catchment area showed positive ones. Temporal beta diversity was also higher when the rate and magnitude of rises and falls in flow was higher in the hydrograph as well as when the number of zero-flow days and the duration of flow rises and falls was higher. C_LIO_LIOverall, our results indicate that temporal beta diversity of freshwater benthic macroinvertebrates is shaped by both long-term hydrological context and spatial context, and that these factors may serve as better predictors of long term community variability than variability in point estimates of environmental measurements. Flow regimes and spatial metrics may provide more environmental context than point-estimate environmental measurements, as the latter may not accurately capture the dynamic conditions that drive variability in metacommunity responses. C_LIO_LIOur study supports the need for biomonitoring efforts at long spatial and temporal timescales, and highlights the need to consider metacommunity change in the management of freshwater systems. C_LI

ecology↗