Thomas E Johnson et al. (2005) International Worm Meeting "Stochastic Effects Make a Big Difference in How Long You Will Live (If You Are a Worm)"

Deqing Wu, Jim Cypser, Shane Rea, Thomas E Johnson

[International Worm Meeting, 2005]

The record for life extension is more than seven-fold and is held by the vanFleteren lab using a combination of environmental intervention (axenic survival medium) and genetic alteration (daf-2 hypomorph). However, neither genes nor environment account for the huge variation in life span typically found within almost every longevity study performed in worms over the last 25 years. This variation is due to chance effects and is largely intractable. We have begun to address this issue using an HSP-16::GFP reporter strain and a Union Biometrica worm sorter. We grow this isogenic strain under liquid culture conditions to minimize environmental variance and induce it using one or two hours of heat. We monitor GFP expression in tens of thousands of individual worms several hours later. We see a huge amount of variance that is entirely non-genetic. When we select the brightest and the dimmest 1 2 % of the population, we find that these worms form two distinct groups with regard to life expectancy and ability to survive additional heat stresses. Other differential effects, as well as causal mechanisms are being sought.

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.

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.

Tax FE et al. (1994) Worm Breeder's Gazette "Some Notes on Mapping Contigs Using Molecular Analysis of Deficiences"

Thomas JH, Tax FE

[Worm Breeder's Gazette, 1994]

Some notes on mapping contigs using molecular analysis of deficiencies Frans Tax and Jim Thomas, Dept. of Genetics, University of Washington, Seattle WA 98195

Thomas JH et al. (1994) Worm Breeder's Gazette "lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein"

Thomas JH, Horvitz HR

[Worm Breeder's Gazette, 1994]

lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein Jeffrey H. Thomas and H. Robert Horvitz, HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA

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

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

[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.

Burglin TR et al. (1993) Worm Breeder's Gazette "ceh-6 Expression and Generation of a Knock-Out"

Plasterk RHA, Ruvkun GB, Burglin TR

[Worm Breeder's Gazette, 1993]

ceh 6 expression and generation of a knock-out Thomas Burglin, Ron Plasterk*, Gary Ruvkun Dept. of Molecular Biology, Wellman 8, Massachusetts General Hospital, Boston, MA, 02114, USA, and *Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.

Park, Sang-Kyu et al. (2009) International Worm Meeting "Novel Pathways Mediating Dietary-Restriction-Induced Longevity in C. elegans: NLP-7 Signaling and Endocytosis by Coelomocytes."

Park, Sang-Kyu, Johnson, Thomas

[International Worm Meeting, 2009]

Dietary restriction (DR) is the most widely used intervention to promote longevity in a diverse range of organisms. Despite this, the mechanisms underlying efficacy of dietary restriction still remain elusive. The SKN-1 transcription factor mediates life extension under DR in Caenorhabditis elegans. We identified downstream targets of SKN-1 using genomic transcriptional profiling (Park et al., in press). Two SKN-1-dependent genes, nlp-7 and cup-4, were required for both resistance to oxidative stress and normal longevity. nlp-7 encodes a neuropeptide-like protein and cup-4 encodes a coelomocyte-specific ion-channel. Here, we report that nlp-7 and cup-4 are specifically required for DR-induced longevity in C. elegans. RNAi of nlp-7 or cup-4 significantly reduces the lifespan of a genetic model of DR, the eat-2 mutant, but has no effect on the lifespan of long-lived mutants having reduced insulin/IGF-1 signaling or dysfunctional mitochondrial electron transport chain. There are several methods for imposing DR in the worm and we found that bacterial dilution also fails to increase the lifespan of nlp-7 or cup-4 mutants. RNAi of genes encoding candidate receptors of NLP-7 and genes involved in coelomocyte endocytosis also specifically shortens the extended lifespan of eat-2 mutant. Based on these results, we conclude that two novel pathways, NLP-7 signaling and endocytosis in coelomocytes, are required for life extension under dietary restriction in C. elegans (supported by grants from the NIA).

Reilly, Molly et al. MicroPubl Biol

Hobert, Oliver, Reilly, Molly

[MicroPubl Biol, 2020]

We have previously described the expression patterns of all but one of the 102 homeobox genes present in the C. elegans genome, using either fosmid-based reporter transgenes or CRISPR/Cas9-engineered gfp reporter alleles (Reilly et al., 2020). The last remaining homeobox gene for which we were initially not able to generate a reporter reagent for is ceh-84 (Reilly et al., 2020). As previously recognized by Thomas Brglin (Hench et al., 2015), ceh-84 codes for an unusual homeodomain protein with two divergent homeodomains (Fig.1D). It likely is a tandem duplicate of the ceh-85 gene, which has been classified as a pseudogene (Fig.1B). ceh-84 has no recognizable homologs in other Caenorhabditis species (Hench et al., 2015). Together with its duplicate, ceh-85, localizes to a large cluster of extensively duplicated genes on chromosome II, described by James Thomas (Thomas, 2006). Most of the duplicated genes code for MATH and BTB type proteins (Fig.1A). The entire cluster seems to be C. elegans-specific (Thomas, 2006) and, apart from a number of pseudogenes, it also contains the C. elegans-specific ceh-81, ceh-82 and ceh-83 homeobox genes (Fig.1A).

Tissenbaum HA et al. (1995) International C. elegans Meeting "GENETIC AND MOLECULAR ANALYSIS OF daf-2 AND daf-16."

Gottlieb S, Lee L, Tissenbaum HA, Ruvkun GB, Lam F

[International C. elegans Meeting, 1995]

We have been studying the genetic interactions between the genes daf-2, daf-23 and daf-16 (Gottlieb and Ruvkun 1994). These genes either act in a branch separate from the daf-11/daf-21 and daf-7 group of the genetic epistasis pathway for dauer formation or further downstream in the pathway ( Riddle et al. 1981; Vowels and Thomas 1992; Thomas et al. 1993; Gottlieb and Ruvkun 1994). Molecular analysis of daf-2, daf-16 as well as daf-23 (see abstract by Morris et al. this meeting) will help to elucidate function (e.g. neurons vs. target tissues) as well as shed light on the complex genetic interactions of these genes.