A5084035153- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- Adipose Tissue and Metabolism
- Dietary Effects on Health
- Spaceflight effects on biology
- Agriculture Sustainability and Environmental Impact
- Tryptophan and brain disorders
- Diet and metabolism studies
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Education Systems and Policy
- Physiological and biochemical adaptations
- Olfactory and Sensory Function Studies
- Genetic Neurodegenerative Diseases
- Nursing Education, Practice, and Leadership
University of Michigan
2017-2024
Michigan United
2019-2022
University of Washington
2012-2015
Seattle University
2012
Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity individuals genetically heterogeneous populations is not well characterized. Here, we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses DR. The was determined for 166 single gene deletion strains Saccharomyces cerevisiae. Resulting changes mean ranged from reduction 79% an increase 103%. Vacuolar pH...
Stabilization of the hypoxia-inducible factor 1 (HIF-1) increases life span and health in nematodes through an unknown mechanism. We report that neuronal stabilization HIF-1 mediates these effects Caenorhabditis elegans a cell nonautonomous signal to intestine, which results activation xenobiotic detoxification enzyme flavin-containing monooxygenase-2 (FMO-2). This prolongevity requires serotonin biosynthetic TPH-1 neurons receptor SER-7 intestine. Intestinal FMO-2 is also activated by...
As the demographics of modern world skew older, understanding and mitigating effects aging is increasingly important within biomedical research. Recent studies in model organisms demonstrate that process frequently modified by an organism's ability to perceive respond changes its environment. Many well-studied pathways influence involve sensory cells, neurons, signal peripheral tissues promote survival during presence stress. Importantly, this activation stress response often sufficient...
Abstract An organism’s ability to perceive and respond changes in its environment is crucial for health survival. Here we reveal how the most well-studied longevity intervention, dietary restriction, acts in-part through a cell non-autonomous signaling pathway that inhibited by presence of attractive smells. Using an intestinal reporter key gene induced restriction but suppressed smells, identify three compounds block food odor effects C. elegans , thereby increasing as mimetics. These...
Abstract Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans , fmo-2 expression increases lifespan and healthspan downstream multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as xenobiotic enzyme, leads to rewiring endogenous metabolism principally changes in one carbon (OCM). These likely relevant, find that genetically modifying OCM enzyme...
Abstract Caenorhabditis elegans is an instrumental research model used to advance our knowledge in areas including development, metabolism, and aging. However, on metabolism and/or other measures of health/aging are confounded by the nematode’s food source lab, live E. coli bacteria. Commonly treatments, ultraviolet irradiation antibiotics, successful preventing bacterial replication, but bacteria can remain metabolically active. The purpose this study develop a inactive for worms that will...
Chronological and replicative aging have been studied in yeast as alternative paradigms for post-mitotic mitotic aging, respectively. It has known more than a decade that cells of the S288C background aged chronologically rich medium reduced lifespan relative to young cells. Here we report replication this observation diploid BY4743 strain background. We further show reduction from chronological is accelerated when are under standard conditions synthetic complete rather medium. The loss...
Summary As in other poikilotherms, longevity C. elegans varies inversely with temperature; worms are longer‐lived at lower temperatures. While this observation may seem intuitive based on thermodynamics, the molecular and genetic basis for phenomenon is not well understood. Several recent reports have argued that lifespan changes across temperatures genetically controlled by temperature‐specific gene regulation. Here, we provide data both corroborate those studies suggest more rule than...
There is growing evidence that stochastic events play an important role in determining individual longevity. Studies model organisms have demonstrated genetically identical populations maintained under apparently equivalent environmental conditions display variation life span can be modeled by the Gompertz-Makeham law of mortality. Here, we report within haploid and diploid wild-type populations, shorter-lived cells tend to arrest a budded state, while unbudded state are significantly...
Abstract Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans , fmo-2 expression increases lifespan and healthspan downstream multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, contrary to its classification as xenobiotic enzyme, leads rewiring endogenous metabolism principally changes in one carbon (OCM). Using computer modeling, identify decreased methylation the...
Abstract An organism’s ability to perceive and respond changes in its environment is crucial for health survival. Here we reveal how the most well-studied longevity intervention, dietary restriction (DR), acts in-part through a cell non-autonomous signaling pathway that inhibited by perception of attractive smells. Using an intestinal reporter key gene induced DR but suppressed smells, identify three compounds block food C. elegans , thereby increasing as mimetics. These clearly implicate...
Abstract The ability of organisms to perceive and respond their environment is crucial long-term survival. Recent studies in model identify signaling pathways that environmental stress cell non-autonomously modify systemic physiology. These often originate the neurons, where key cells monitor external for changes including food availability, air-quality, presence dangerous toxins. Our previous work identified a role serotonin induction flavin-containing monooxygenase-2 (fmo-2) downstream...
Recent studies in multiple organisms identify pathways that link the perception of stress by nervous system with signaling networks modify health and longevity. Several these longevity involve monoamine neurotransmitter serotonin as a key molecule. With knowledge plays critical role regulating aging, our current research focuses on using C. elegans to understand map how neuronal signal improve long-term health. Our previous work showed induction flavin -containing monooxygenase-2 (fmo-2),...
Abstract HIF-1-mediated adaptation to changes in oxygen availability is a critical aspect of healthy physiology. HIF regulated by conserved mechanism whereby EGLN/PHD family members hydroxylate an oxygen-dependent manner, targeting it for ubiquitination Von-Hippel-Lindau (VHL) members, leading its proteasomal degradation. The activity the only C. elegans PHD member, EGL-9, also hydrogen sulfide sensing cysteine-synthetase-like protein, CYSL-1, which is, turn, RHY-1/acyltransferase. Over last...
Abstract An organism’s ability to perceive and respond changes in its environment is crucial for health survival. Our approach identify molecular mechanisms of aging focus on common downstream multiple pathways. This led our discovery a gene, flavin-containing monooxygenase (fmo)-2, that both necessary sufficient increase lifespan healthspan several longevity interventions, including dietary restriction hypoxia. Surprisingly, we also find hypoxia models, fmo-2 induced by cell non-autonomous...
Abstract An organism’s ability to respond stress is crucial for long-term survival. These responses are coordinated by distinct but overlapping pathways, many of which also regulate longevity across taxa. Our previous work identified a cell non-autonomous signaling pathway led the hypoxia-inducible factor and resulting in induction flavin-containing monooxygenase-2 (fmo-2) promote health longevity. current identifies downstream dietary restriction (DR) that relies on fmo-2 We now find these...