Johnson, Christina K. et al. (2021) MicroPubl Biol

Bianchi, Laura, Johnson, Christina K., Miller III, David M.

[MicroPubl Biol, 2021]

For Johnson, CK; Miller, DD; Bianchi, L (2021). Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d). microPublication Biology. 10.17912/micropub.biology.000412.

Johnson TE (2005) J Gerontol A Biol Sci Med Sci "Genes, phenes, and dreams of immortality: the 2003 Kleemeier Award lecture."

Johnson TE

[J Gerontol A Biol Sci Med Sci, 2005]

The 2002 Kleemeier Award from the Gerontological Society of America was awarded to Thomas E. Johnson, PhD, of the University of Colorado at Boulder. Dr. Johnson was the pioneer who first applied genetic analyses to the study of the aging processes in Caenorhabditis elegans and who introduced the nematode as an aging model. Longer life span was chosen as a surrogate marker for slowed aging. Here Dr. Johnson describes his role(s) in the isolation of age-1, the first longevity mutant, which can more than double the life span and which slows the rate of aging more than twofold. He also reviews research suggesting conservation of function and applicability to intervention by pharmacological targeting of the Age-1 pathway. Current work by biotechnology companies targets this and other basic discoveries in an attempt to postpone human aging.

Coleman-Hulbert, Anna L et al. MicroPubl Biol

Sedore, Christine A, Banse, Stephan A, Guo, Max, Coleman-Hulbert, Anna L, Driscoll, Monica, Phillips, Patrick C, Lithgow, Gordon J, Johnson, Erik

[MicroPubl Biol, 2019]

The authors, Coleman-Hulbert, AL; Johnson, E; Sedore, CA; Banse, SA; Guo, M2; Driscoll, M3; Lithgow, GJ; and Phillips, PC, submit the following correction. The first reference in the methods paragraph should be (Lucanic et al., 2017; Plummer et al., 2017) and should not be letteredaccordingly. We assayed lifespan in response to imatinib mesylate exposure in three Caenorhabditis species in triplicate using our previously published workflow (Lucanic et al. 2017a; b). should be corrected to: We assayed lifespan in response to imatinib mesylate exposure in three Caenorhabditis species in triplicate using our previously published workflow (Lucanic et al., 2017; Plummer et al., 2017).

Woodruff, Gavin et al. (2021) International Worm Meeting "Widespread changes in gene expression accompany body size evolution in nematodes"

Phillips, Patrick, Johnson, Erik, Woodruff, Gavin, Willis, John

[International Worm Meeting, 2021]

Body size is a fundamental trait that drives multiple evolutionary and ecological patterns. Caenorhabditis inopinata is a fig-associated nematode that is exceptionally large relative to other members of the genus, including C. elegans. We previously showed that C. inopinata is large primarily due to postembryonic cell size expansion that occurs during the larval-to-adult transition. Here, we describe gene expression patterns in C. elegans and C. inopinata throughout this developmental period to understand the transcriptional basis of body size change. We performed RNAseq in both species across the L3, L4, and adult stages. Most genes are differentially expressed across all developmental stages, consistent with C. inopinata's divergent ecology and morphology. We also used a model comparison approach to identify orthologs with divergent dynamics across this developmental period between the two species. Notably, among such genes were two transcription factors previously shown in C. elegans to be important for body size that are regulated by the TGF-beta signaling pathway. Multiple hypodermal collagens were also observed to harbor divergent developmental dynamics across this period. C. elegans-specific ontology enrichment reveals genes with divergent developmental dynamics tend to be expressed in neurons and regulate behavior; they also include genes important for molting and body morphology. A comparison of such genes with previous C. elegans experiments reveals overlap with stress response, developmental timing, and small RNA/chromatin regulation. These results have identified candidate genes that will be further investigated to test their roles in cell size divergence and broaden our understanding of the genetic bases of body size evolution.

Murakami S et al. (1996) West Coast Worm Meeting "LIFE-EXTENSION PATHWAY IN C.ELEGANS"

Dames SA, Johnson TE, Murakami S, Tedesco PM, Duhon SA

[West Coast Worm Meeting, 1996]

Life extension is conferred either by mutants extending adult life (Age), including age-1, daf-2, daf-23, daf-28, spe-26, and an allele of clk-1. Another mode of life extension is conferred by mutants delaying developmental stage (Clk), including clk-1, clk-2, clk-3, gro-1(Wong et al., 1995; Lakowski and Hekimi, 1996). Three groups have identified a life-extension pathway formed by some Daf mutations (Dorman et al., 1995; Larsen et al., 1995; Murakami and Johnson, 1996). We found that the pathway is not limited to Daf mutations but includes other types of the Age mutants (Murakami and Johnson, 1996). Interestingly, the pathway confers UV resistance, suggesting that UV resistance is a good indicator of Age. It is also consistent with the hypothesis that stress resistance is a rate limiting factor determining longevity. We are also testing whether the Age-pathway can confer other types of stress such as H2O2 and heat.

Hooper C (1991) The Journal of NIH Research "Old-aged mutant ninja nematodes' cool anti-age gene."

Hooper C

[The Journal of NIH Research, 1991]

Cowabugna, dudes! Those lean, gene-revealing machines have scored a most totally excellent victory in the battle to understand aging. We are, of course, talking about mutant ninja nematodes here. At a conference on aging in January at Cold Spring Harbor's Banbury Center, Thomas Johnson of the Institute for Behavioral Genetics at the University of Colorado in Boulder brought some dudes and dudettes from Capitol Hill up to date on the latest awesome achievements of the bodacious beasts know as Caenorhabditis elegans.

Cowden C et al. (1986) Worm Breeder's Gazette "a CCK-like neuropeptide in Ascaris."

Stretton AOW, Cowden C

[Worm Breeder's Gazette, 1986]

Our aim is to obtain peptides of known sequence from Ascaris in order to determine their mode of action using electrophysiological methods. Since McIntire and Horvitz (C. elegans CSH Abstracts 1985) showed that cholecystokinin-like immunoreactivity (CCK-LI) is present in certain neurons in C. elegans, we are initially investigating the role of a CCK-like peptide (CCK-LP) in the nervous system of Ascaris using anti-CCK8 antisera to detect and localize CCK-LI. Using the methods developed by Johnson (see Johnson and Stretton, Soc. Neurosci. Abstr. 9: 302; Sithigorngul, Johnson and Stretton, C. elegans CSH Abstracts 1985) we find that in Ascaris, CCK-LI is concentrated in 2 cells (AVF cells) in the ventral nerve cord, in 3 cells in the ventral ganglion, in 4 processes in the ventral cord, and in 2 processes in the lateral line. Thus the CCK-LP is concentrated in a small minority of the 180 neurons present in the anterior region of adult Ascaris.We have developed a procedure for extracting the CCK- LP from C. elegans and fractionating the extract on a C18 cartridge. High voltage paper electrophoresis shows that added radioiodinated CCK8 is chemically intact after this extraction and after fractionation. The CCK-LP was separated from more hydrophilic components with a 20-40% gradient of acetonitrile on reversed phase HPLC. RIA's detected CCK-LI associated with a peak of optical density. Addition of authentic CCK8 (non-sulfated) to the sample showed that the RIA-positive peak was close to, but distinctly separate from, CCK8. Assuming that the specific immunoreactivity of nematode CCK-LP and mammalian CCK8 is the same, we can obtain 100 pmoles from 60g of C. elegans. From this crude estimate, it seems that the levels of recoverable peptide are sufficient for amino acid sequence determination which is now our top priority.

Banse, Stephen et al. (2019) International Worm Meeting "The role of FMRFamide-like signaling in regulating lifespan in C. elegans."

Johnson, Erik, Sedore, Christine, Phillips, Patrick, Banse, Stephen, Robinson, Kristin, Coleman-Hulbert, Anna

[International Worm Meeting, 2019]

Neuronal control of behavior is potentiated through many different classes of signaling molecules. In vitro characterization of one such class, FMRFamide-like peptides (flp), has identified numerous peptides that can regulate the rate of pumping of the C. elegans feeding organ, the pharynx. Because slowed pumping can induce dietary restriction, a widely conserved intervention that extends lifespan, we performed a survey of the available flp-gene mutants to identify regulators of lifespan. Of the 22 mutants examined, three strains were long lived, defined by lifespans greater than 120% of N2. Four strains were short lived, defined by lifespans shorter than 90% of N2. Of the seven genes with biochemical data showing efficacious alteration of pump frequency at ?100nM, six exhibited altered lifespans. The one exception, flp-8, appears to have a developmentally restricted expression pattern and may not be expressed in adulthood. This analysis suggests that modulation of neuronal flp signaling is a candidate for pharmacological interventions seeking to extend lifespan.

Johnson TE (2013) Exp Gerontol "25 years after age-1: genes, interventions and the revolution in aging research."

Johnson TE

[Exp Gerontol, 2013]

This communication will briefly review more than 30 years of research on aging using the nematode Caenorhabditis elegans ("The Worm") as carried out in the labs of Tom Johnson. We will highlight research directions initiated in the 1980's, which were exciting for those of us trying to turn over a new leaf in aging research. In this narrative, I will discuss primarily the science that I and my lab have been involved with for the last 30 years. This area has been fascinating to those studying the sociology of science as modern aging research has moved to replace the simplistic, poorly controlled and outright fictitious approaches seen in much of the previous aging research.

Banse, Stephen et al. (2021) International Worm Meeting "All trans retinoic acid extends C. elegans lifespan in an aak-2 and hsf-1 dependent manner by modulating metabolism."

Coleman-Hulbert, Anna, Banse, Stephen, Phillips, Patrick, Segerdell, Erik, Willis, John, Jones, E Grace, Sedore, Christine, Johnson, Erik

[International Worm Meeting, 2021]

Aging is a pan-metazoan phenotype that significantly impacts human health and society. Across metazoans, the rate of aging is influenced by a zero-sum allocation of resources between maintenance and growth. We therefore sought to manipulate signaling components from conserved resource allocation systems to identify potential anti-aging interventions. Here we present the exploration of the endogenous vitamin A derivative all trans Retinoic Acid (atRA), and its role promoting gluconeogenesis, as a modulator of aging in Caenorhabditis elegans. We found that supplementation with atRA extends lifespan in a concentration dependent manner. As predicted based on the conserved pathway, atRA acts independently of daf-16, but it does require the conserved AMP sensor aak-2, consistent with a change in metabolism and energy storage. The observed shift in metabolism comes at a reproductive cost, consistent with a redirection of energy resources to somatic maintenance. This approach shows that the manipulation of a conserved metabolic regulatory circuit by co-opting endogenous signaling molecules can extend lifespan.