Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories. Reproducibility between test sites is high, whereas individual trial reproducibility is relatively low. Of ten pro-longevity chemicals tested, six significantly extend lifespan in at least one strain. Three reported dietary restriction mimetics are mainly effective across C. elegans strains, indicating species and strain-specific responses. In contrast, the amyloid dye ThioflavinT is both potent and robust across the strains. Our results highlight promising pharmacological leads and demonstrate the importance of assessing lifespans of discrete cohorts across repeat studies to capture biological variation in the search for reproducible ageing interventions.

The oilseed species Thlaspi arvense (pennycress)-a weed that was only recently removed from the wild-has the potential to provide new sources of food and bioproducts when grown as a winter cover crop. Domestication of wild species has historically taken hundreds to thousands of years, but by making use of large-scale high-throughput comparative gene and phenotype analyses, along with recently developed technological tools, it has been possible to greatly accelerate this process. By taking advantage of extensive gene and phenotype knowledge in the related plant Arabidopsis, mutations for early maturity, reduced pod shatter, reduced seed glucosinolates and improved fatty acid composition were identified. Progress has been made to rapidly stack these traits in order to domesticate the plant, allowing it to fit within current crop cycles and to have improved seed harvestability and nutritional content. Pennycress, domesticated as a winter cover crop, may provide new sources of food, animal feed and bioproducts-and solutions to food security.

Thlaspi arvense (pennycress) has the potential for domestication as a new oilseed crop. Information from an extensive body of research on the related plant species Arabidopsis can be used to greatly speed this process. Genome-scale comparisons in this paper documented that pennycress and Arabidopsis share similar gene duplication. This finding led to the hypothesis that it should be possible to isolate Arabidopsis-like mutants in pennycress. This proved to be true, as forward genetic screens identified floral and vegetative pennycress mutants that were similar to mutants found in Arabidopsis. Extending this approach, it was shown that most of the pennycress genes responsible for the formation of oxidized tannins could be rapidly identified. The causative mutations in the pennycress mutants could be identified either by PCR amplification of candidate genes or through whole-genome sequencing (WGS) analysis. In all, WGS was used to characterize 95 ethyl methane sulfonate mutants, which revealed a mutation rate of 4.09 mutations per megabase. A sufficient number of non-synonymous mutations were identified to create a mutant gene index that could be used for reverse genetic approaches to identify pennycress mutants of interest. As proof of concept, a Ta-max3-like dwarf mutant and Ta-kcs5/cer60-like wax mutants deficient in the biosynthesis of long chain fatty acids were identified. Overall, these studies demonstrate that translational genomics can be used to promote the domestication of pennycress. Furthermore, the ease with which important findings could be made in pennycress makes this species a new potential model plant.

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays. With an interest in increasing throughput, we explored automation with flatbed scanner-based Automated Lifespan Machines (ALMs). We used ALMs to measure survivorship of 22 Caenorhabditis strains spanning three species. Additionally, we tested five chemicals that we previously found extended lifespan in manual assays. Overall, we found similar sources of variation among trials for the ALM and our previous manual assays, verifying reproducibility of outcome. Survival assessment was generally consistent between the manual and the ALM assays, although we did observe radically contrasting results for certain compound interventions. We found that particular lifespan outcome differences could be attributed to protocol elements such as enhanced light exposure of specific compounds in the ALM, underscoring that differences in technical details can influence outcomes and therefore interpretation. Overall, we demonstrate that the ALMs effectively reproduce a large, conventionally scored dataset from a diverse test set, independently validating ALMs as a robust and reproducible approach toward aging-intervention screening.Electronic supplementary materialThe online version of this article (10.1007/s11357-019-00108-9) contains supplementary material, which is available to authorized users.

Field pennycress ( Thlaspi arvense L.) is currently being developed as a new cold‐tolerant oilseed crop. In natural populations, pennycress, like many Brassicaceae relatives, can exhibit either a winter or spring annual phenotype. Pennycress is a diploid relative of Arabidopsis thaliana, a model species that has been used to study many adaptive phenotypes, including flowering time and developmental timing. In Arabidopsis and other Brassicaceae species, mutations in negative regulators of flowering, including FLOWERING LOCUS C and FRIGIDA can cause the transition to a spring annual habit. The genetics underlying the difference between spring and winter annual pennycress lines are currently unknown. Here, we report the identification of four natural alleles of FLC in pennycress that confer a spring annual growth habit identified through whole genome sequencing, cosegregation analyses, and comparative genomics. The global distribution of these spring annual alleles of FLC suggests that the spring annual growth habit has arisen on several independent occasions. The two spring annual FLC alleles present in European accessions were only identified in North American accessions collected in southern Montana, which indicates accessions harboring these two alleles were introduced to North America, likely after pennycress became a widespread species on the continent. These findings provide new information on the natural history of the introduction and spread of spring annual pennycress accessions from Europe into North America. At the molecular level, these findings are important for the ongoing development of pennycress as a winter annual crop. An enhanced understanding of the regulation of flowering in this species should allow for the fine‐tuning of flowering in commercial varieties.

No abstract

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays. With an interest in increasing throughput, we explored automation with flatbed scanner-based Automated Lifespan Machines (ALMs). We used ALMs to measure survivorship of 22 Caenorhabditis strains spanning three species. Additionally, we tested five chemicals that we previously found extended lifespan in manual assays. Overall, we found similar sources of variation among trials for the ALM and our previous manual assays, verifying reproducibility of outcome. Survival assessment was generally consistent between the manual and the ALM assays, although we did observe radically contrasting results for certain compound interventions. We found that particular lifespan outcome differences could be attributed to protocol elements such as enhanced light exposure of specific compounds in the ALM, underscoring that differences in technical details can influence outcomes and therefore interpretation. Overall, we demonstrate that the ALMs effectively reproduce a large, conventionally scored dataset from a diverse test set, independently validating ALMs as a robust and reproducible approach towards aging-intervention screening.

BackgroundVariation in body size is thought to be a major driver of a wide variety of ecological and evolutionary patterns, including changes in development, reproduction, and longevity. Additionally, drastic changes in natural context often have profound effects on multiple fitness-related traits. Caenorhabditis inopinata is a recently-discovered fig-associated nematode that is unusually large relative to other members of the genus, including the closely related model system C. elegans. Here we test whether the dramatic increase in body size and shift in ecological context has led to correlated changes in key life history and developmental parameters within this species.ResultsUsing four developmental milestones, C. inopinata was found to have a slower rate of development than C. elegans across a range of temperatures. Despite this, C. inopinata did not reveal any differences in adult lifespan from C. elegans after accounting for differences in developmental timing and reproductive mode. C. inopinata fecundity was generally lower than that of C. elegans, but fitness improved under continuous-mating, consistent with sperm-limitation under gonochoristic (male/female) reproduction. C. inopinata also revealed greater fecundity and viability at higher temperatures.ConclusionConsistent with observations in other ectotherms, slower growth in C. inopinata indicates a potential trade-off between body size and developmental timing, whereas its unchanged lifespan suggests that longevity is largely uncoupled from its increase in body size. Additionally, temperature-dependent patterns of fitness in C. inopinata are consistent with its geographic origins in subtropical Okinawa. Overall, these results underscore the extent to which changes in ecological context and body size can shape life history traits.Electronic supplementary materialThe online version of this article (10.1186/s12862-019-1388-1) contains supplementary material, which is available to authorized users.