Eli Hagedorn’s research while affiliated with University of Alabama and other places

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Publications (3)


Figure 2. Injection of D. melanogaster males with FHV decreases levels of organismal OCR in both young and aged flies, but OCR is also influenced by the time post-treatment in young flies and the time of the day during which measurements are performed. (A-D) Graphs showing pairwise comparisons of variables with significant main effect on OCR: 'Treatment' (A), 'Time PostTreatment' (B), and 'Zeitgeber Time' (C) and interaction effect: 'Age * Time Post-Treatment' (D). OCR measurement values for individual datapoints are plotted. Significant comparisons were determined by post hoc Tukey-Kramer tests within each panel as described in methods. Each symbol represents an individual OCR measurement on a fly.
Figure 3. FHV-injected cohorts display higher mortality compared to controls throughout the experiment, and mortality of young and aged cohorts is comparable among treatment groups. (A) Bar graphs showing the distribution of individual survival within each 'Treatment' group at 24 h, 48 h and 72 h post-treatment in both young and old flies (n = 40 starting in each age-by-treatment group). (B) Survival curves comparing mortality of Tris-and FHV-injected flies recorded during the respirometry experiment (n = 40 flies per experimental condition) and during an independent survival assay carried in parallel (n = 30 flies per experimental condition). A significant difference between 5-and 30-days-old flies is observed following FHV infection (p < 0.0001), but not Tris injection (p = 0.648) in the parallel survival assay, based on a log-rank test. At 3 days post-treatment, no significant difference is observed between young and aged FHVinfected flies in both the respirometry experiment (p = 0.827) and the parallel survival assay (p = 0.562) based on a log-rank test.
Figure 4. Differences in OCR could influence the outcome of FHV infection. (A, B) Graphs showing pairwise comparisons of variables with significant main effect on OCR at 24 h: 'Treatment' (A) and significant interaction effect on OCR: 'Treatment * Survival 48-and 72-hours' (B). OCR measurement values for individual datapoints are plotted. Significant comparisons were determined by post hoc Tukey-Kramer tests as described in methods. Each symbol represents an individual OCR measurement on a fly.
RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males
  • Article
  • Full-text available

March 2023

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57 Reads

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1 Citation

Aging

Eli Hagedorn

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Dean Bunnell

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Beate Henschel

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[...]

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Stanislava Chtarbanova

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due to impaired disease tolerance. Using this aged host-virus model, we conducted longitudinal, single-fly respirometry studies to determine if metabolism impacts infection outcomes. Analysis using linear mixed models on Oxygen Consumption Rate (OCR) following the first 72-hours post-infection showed that FHV modulates respiration, but age has no significant effect on OCR. However, the longitudinal assessment revealed that OCR in young flies progressively and significantly decreases, while OCR in aged flies remains constant throughout the three days of the experiment. Furthermore, we found that the OCR signature at 24-hours varied in response to both experimental treatment and survival status. FHV-injected flies that died prior to 48-or 72-hours measurements had a lower OCR compared to survivors at 48-hours. Our findings suggest the host's metabolic profile could influence the outcome of viral infections.

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Figure 1 A.
Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila

April 2021

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47 Reads

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4 Citations

G3 Genes Genomes Genetics

Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections with some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster is able to mount potent and evolutionarily conserved innate immune defenses against a variety of microorganisms including viruses and serves as an excellent model organism for studying host-pathogen interactions. With its relatively short lifespan, Drosophila also is an organism of choice for aging studies. Despite numerous advantages that this model offers, Drosophila has not been used to its full potential to investigate the response of the aged host to viral infection. Here we show that, in comparison to younger flies, aged Drosophila succumb more rapidly to infection with the RNA-containing Flock House Virus (FHV) due to an age-dependent defect in disease tolerance. Relative to younger individuals, we find that older Drosophila mount transcriptional responses characterized by differential regulation of more genes and genes regulated to a greater extent. We show that loss of disease tolerance to FHV with age associates with a stronger regulation of genes involved in apoptosis, some genes of the Drosophila Immune deficiency (IMD) NF-kB pathway and genes whose products function in mitochondria and mitochondrial respiration. Our work shows that Drosophila can serve as a model to investigate host-virus interactions during aging and furthermore sets the stage for future analysis of the age-dependent mechanisms that govern survival and control of virus infections at older age.


Figure 3
Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila

September 2020

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34 Reads

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1 Citation

Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections with some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster is able to mount potent and evolutionarily conserved innate immune defenses against a variety of microorganisms including viruses and serves as an excellent model organism for studying host-pathogen interactions. With its relatively short lifespan, Drosophila also is an organism of choice for aging studies. Despite numerous advantages that this model offers, Drosophila has not been used to its potential to investigate the response of the aged host to viral infection. Here we show that in comparison to younger flies, aged Drosophila succumb more rapidly to infection with the RNA-containing Flock House Virus (FHV) due to an age-dependent defect in disease tolerance. In comparison to younger individuals, we find that older Drosophila mount larger transcriptional responses characterized by differential regulation of more genes and genes regulated to a greater extent. Our results indicate that loss of disease tolerance to FHV with age possibly results from a stronger regulation of genes involved in apoptosis, activation of the Drosophila Immune deficiency (IMD) NF-kB pathway or from downregulation of genes whose products function in mitochondria and mitochondrial respiration. Our work shows that Drosophila can serve as a model to investigate host-virus interactions during aging and sets the stage for future analysis of the age-dependent mechanisms that govern survival and control of virus infections at older age.

Citations (2)


... Subsequently, we assessed the metabolic rate by monitoring the whole-body consumption rate of each fly using the Loligo Microplate (24-well plate) Respirometry System (Loligo ® Systems, Viborg, Denmark) at the University of Alabama at Birmingham Small Animal Phenotyping Core. The protocol details are reported in [43]. Briefly, oxygen concentration was measured in each well for 60 min, with the first 30 min of measurements excluded from the analysis to allow each fly to acclimate in a new environment and thereby minimize stress. ...

Reference:

The Impact of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Metabolic Rate in Drosophila melanogaster
RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males

Aging

... We previously used pathogenic infection of D. melanogaster with the Flock House virus (FHV) to investigate the changes in antiviral innate immune responses of aged hosts [19]. FHV is an Alphanodavirus that contains a bipartite, positive-sense, single-stranded RNA genome [20]. ...

Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila

G3 Genes Genomes Genetics