Pickett, Christopher L. et al. (2009) International Worm Meeting "Increasing wild type hermaphrodite brood size does not affect life span."

Kornfeld, Kerry, Pickett, Christopher L., Collier, Sara, Armstead, Brinda L.

[International Worm Meeting, 2009]

Aging is characterized by a progressive decline of tissue organization and function that correlates with chronological age. The link between aging, progeny production, and reproductive decline, however, is controversial. Antagonistic pleiotropy was proposed in the 1950s and theorized that extending life span required a reduction in progeny production, and vice versa. Consistent with this theory, loss- or reduction-of-function mutations in insulin signaling, mitochondrial electron transport, or caloric intake extend life span and often reduce progeny production in a number of organisms. However, the effects of increasing progeny production on life span have not been adequately investigated. To address this, we conducted longitudinal studies using C. elegans N2 hermaphrodites mated to N2 males, and we analyzed brood size, reproductive span, fast body movement span, pharyngeal pumping span, and life span. In addition, hermaphrodites were unmated or mated to sterile fer-6(hc6) males-these animals mate but do not transfer viable sperm. The brood sizes and reproductive spans of mated hermaphrodites were nearly double those of unmated or fer-6(nc6) mated hermaphrodites. We also observed that the fast body movement, pharyngeal pumping, and life spans did not significantly differ among unmated hermaphrodites or those mated to N2 males or fer-6(hc6) males. These data suggest that doubling brood size and extending the reproductive period does not decrease life span, contrary to the predictions of antagonistic pleiotropy. Additionally, our preliminary data suggest that different E. coli strains can increase cross brood size. Animals grown on HT115 have larger cross brood sizes than those grown on OP50. We draw two conclusions from these data. First, animals grown on OP50 are not maximizing their reproductive potential. Second, brood size and life span are not involved in a trade-off in hermaphrodites grown on food that does not maximize their reproductive potential. We are currently testing other bacterial strains and species to determine the maximal level of cross progeny production and the effect on life span. Furthermore, in order to analyze reproduction and life span in C. elegans populations, we are validating a liquid culture system where we control food, predation, and the environment.

Murphy, John Thomas et al. (2009) International Worm Meeting "Identification of Mutations in Caenorhabditis elegans That Cause Resistance to High Levels of Dietary Zinc and Analysis Using a Genomewide Map of Single Nucleotide Polymorphisms Scored by Pyrosequencing."

Armstead, Brinda L., Kornfeld, Kerry, Murphy, John Thomas, Schneider, Daniel L., Bruinsma, Janelle J., Davis, Diana E.

[International Worm Meeting, 2009]

Zinc plays many critical roles in biological systems: zinc bound to proteins has structural and catalytic functions, and zinc is proposed to act as a signaling molecule. Because zinc deficiency and excess result in toxicity, animals have evolved sophisticated mechanisms for zinc metabolism and homeostasis. However, these mechanisms remain poorly defined. To identify genes involved in zinc metabolism, we conducted a forward genetic screen for chemically induced mutations that cause Caenorhabditis elegans to be resistant to high levels of dietary zinc. Nineteen mutations that confer significant resistance to supplemental dietary zinc were identified. To determine the map positions of these mutations, we developed a genomewide map of single nucleotide polymorphisms (SNPs) that can be scored by the high-throughput method of DNA pyrosequencing. This map was used to determine the approximate chromosomal position of each mutation, and the accuracy of this approach was verified by conducting three-factor mapping experiments with mutations that cause visible phenotypes. This is a generally applicable mapping approach that can be used to position a wide variety of C. elegans mutations. The mapping experiments demonstrate that the 19 mutations identify at least three genes that, when mutated, confer resistance to toxicity caused by supplemental dietary zinc. It is notable that some zinc metabolism genes function in the metabolism of other metals. Preliminary genetic analysis with physiologically relevant metals such as iron, copper and selenium has confirmed that the mutations are specific to zinc metabolism. This research fills a critical need in the field of metal research, since there is a lack of understanding of how organisms cope with high levels of dietary zinc. These genes are likely to be involved in zinc metabolism, and the analysis of these genes will provide insights into mechanisms of zinc toxicity.

Scharf, Andrea et al. (2021) International Worm Meeting "A population state shift supports aging as a cause of adult death"

Tan, Chieh-Hsiang, Scharf, Andrea, Brady, Brian, Wilson, Andrea, Schneider, Daniel, DiAntonio, Gabe, Sanchez, Francesca, Ram, Natasha, Jin, He, Armstead, Brinda, Kocsisova, Zuzana, Kornfeld, Kerry

[International Worm Meeting, 2021]

Birth and death drive population dynamics and determine whether a population survives or is doomed for extinction. Individual traits that influence development, diapause, reproduction, aging and lifespan must impact the age structure and survival of a population. However, the relationships between individual traits and population dynamics are still a major challenge in the emerging field of ecology-development (eco-devo), because wild populations exist in complex ecosystems that are challenging to investigate and undesirable to manipulate. Here, we introduce a laboratory ecosystem based on the model organism C. elegans that can be used to measure and manipulate worm populations over hundreds of generations. To complement this experimental system, we developed a computational simulation that realistically models the ecosystem and makes it possible to monitor the life history of every single worm in the population. With this integrated systems approach, we investigated the role of aging in population dynamics. The first question we addressed was why some populations support old animals whereas, in other populations, all animals die young. We discovered that old age as a cause of death is influenced by three conditions: maximum lifespan, rate of adult culling, and progeny number/food stability. More specifically, the populations displayed an unexpected tipping point for aging as the primary cause of adult death. In populations with high progeny survival and regular starvation almost all adults died young. In contrast, a reduction of progeny survival over the tipping point caused a dramatic shift in the population with the consequence that nearly all adults died of old age. By defining these conditions, we establish a conceptual framework that explains why animals as different as mayflies and elephants die of old age in the wild. In conclusion, we created a powerful experimental platform to investigate the relationships between individual developmental processes, developmental plasticity, and population dynamics including extinction.