Shoyama T et al. (2007) Mech Ageing Dev "Basic principle of the lifespan in the nematode C. elegans."

Shoyama T, Ishii N, Suda H, Yokota S, Ozaki T

[Mech Ageing Dev, 2007]

We present a biophysical model based on the principles of fluctuation and regulation to explain the effect of stochastics on survival. The model is a good fit for the survivorship and mortality rates observed in the nematode Caenorhabditis elegans. A parameter included in the theory, which is called the fluctuation constant, correlates well with a change (or declining rate) of respiration with age, which we term the physiological decline rate. The square of the physiological decline rate is proportional to the reciprocal of the fluctuation constant as revealed in a diffusion equation. In addition, the maximum and mean life spans are proportional to the reciprocal of the decline rate. The framework involved in the fluctuation theory is compatible with the existence of a regulatory system such as that acting in the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway during adulthood, and that sensing, switching, and memorizing the rate of mitochondrial respiration early in life.

Shoyama T et al. (2009) Exp Gerontol "Decline in oxygen consumption correlates with lifespan in long-lived and short-lived mutants of Caenorhabditis elegans."

Shoyama T, Shimizu Y, Suda H

[Exp Gerontol, 2009]

In humans, the basal energy metabolism is thought to decline linearly with age. On the other hand, in the nematode Caenorhabditis elegans, two research groups reported independently that it declined exponentially. In this study, furthermore, we used various lifespan-mutant strains to determine whether the previous conclusion is more likely to be true. We can indirectly estimate the metabolic energy by conveniently measuring the oxygen consumption rates of C. elegans using an optical apparatus. From the profile of respiratory rates as a function of age, we can quantitatively isolate the physiological decline rate, lambda, that exponentially represents the decay rate of respiratory activity with age. In addition, quantitative analysis indicates that the respiratory activity of worms has a finite value in advanced age. We also show that the maximum and mean lifespans strongly correlate with the reciprocal of the lambda. These findings offer crucial biochemical evidence for a molecular mechanism at work in biological aging. Consequently, we here propose a mechanism based on a chemical reaction and offer a definition of the physiological decline rate and the finiteness of respiratory activity in advanced age.

Shimizu, Y. et al. (2009) International Worm Meeting "How is the onset of biodemographic aging determined?"

Shimizu, Y., Suda, H., Shoyama, T., Hyodo, M.

[International Worm Meeting, 2009]

We have derived the equation of lifespan including the regulation system of aging such as a switching, timing, and memory. Indeed, in our model, two important parameters (t0 and z) are contained (Shoyama et al., Mech. Ageing Dev. 128 (2007) 529-537). The one represents the onset of demographic aging. We have proved that another is proportional to the reciprocal of physiological decline rate. However, the biological meaning of the former parameter remains unclear. Thus, to address this issue, we approach from understanding the regulation mechanism at the molecular level. In this work, we used the long-lived daf-2 mutant strain. Interestingly, when we quantitatively analyzed the survival curve of this mutant using the equation of lifespan, it was composed of two distinct components. The first component was close to that of daf-16 or wild-type. This specific feature has to become a crucial key to perform our aim. On the other hand, we observed a periodic fluctuation in metabolism energy and body size after maturation. The heterogeneity revealed in biodemographic data seems to be concerned with this finding. Thus, to investigate how the onset of biodemographic aging is determined, we quantitatively analyze the survival curves obtained by varing the timing of daf-16-RNAi feeding, using the equation of lifespan.

Suda H et al. (2009) Biophysics (Nagoya-shi) "Analyzing observed or hidden heterogeneity on survival and mortality in an isogenic C. elegans cohort."

Shimizu Y, Suda H, Shoyama T

[Biophysics (Nagoya-shi), 2009]

It is generally difficult to understand the rates of human mortality from biological and biophysical standpoints because there are no cohorts or genetic homogeneity; in addition, information is limited regarding the various causes of death, such as the types of accidents and diseases. Despite such complexity, Gompertz's rule is useful in humans. Thus, to characterize the rates of mortality from a demographic viewpoint, it would be interesting to research a single disease in one of the simplest organisms, the nematode C. elegans, which dies naturally under identically controlled circumstances without predators. Here, we report an example of the fact that heterogeneity on survival and mortality is observed through a single disease in a cohort of 100% genetically identical (isogenic) nematodes. Under the observed heterogeneity, we show that the diffusion theory, as a biophysical model, can precisely analyze the heterogeneity and conveniently estimate the degree of penetrance of a lifespan gene from the biodemographic data. In addition, we indicate that heterogeneity models are effective for the present heterogeneous data.

Shouyama, T. et al. (2009) International Worm Meeting "Quantitatively analyzing the respiratory activity with age in a C. elegans cohort."

Shouyama, T., Suda, H., Horikoshi, T.

[International Worm Meeting, 2009]

Metabolic energy in humans is thought to linearly decline with age and to become zero at maximum lifespan. However, in C. elegans, it has been reported that it exponentially decays (B. P. Braeckman et al., 2002; T. Shoyama et al., 2007). To clarify a relationship between lifespan and aging from an energetic view, we measure oxygen consumption rates, or metabolic energy, as a function of age by using an optical oxygen-concentration-measurement apparatus that was originally developed in our laboratory. In this work, furthermore, we demonstrate whether this conclusion is established against various C. elegans mutant strains. As the present experimental condition, worms were grown on a UV-killed-bacterial lawn from hatching. We carefully improved the experimental condition to remove live bacteria as thoroughly as possible. As a result, we find that oxygen consumption rates exponentially decays after maturity, and those are closely related to mean and maximum lifespans. Here, we defined the physiological decline rate,l. We also confirm that the respiratory activity is maintained in a finite value even at older age. We quantitatively analyze using the equation of lifespan and discuss in more details about this difference between humans and C. elegans. References B. P. Braeckman et al., 2002. Assaying metabolic activity in ageing Caenorhabditis elegans. Mech. Ageing Dev. 123, 105-119. T. Shoyama et al., 2007. Basic principle of the lifespan in the nematode C. elegans. Mech. Ageing Dev. 128, 529-537.

Samuel ADT et al. (2003) J Neurosci "Synaptic activity of the AFD neuron in Caenorhabditis elegans correlates with thermotactic memory."

Murthy VN, Samuel ADT, Silva RA

[J Neurosci, 2003]

Thermotactic behavior in Caenorhabditis elegans is sensitive to both a worm's ambient temperature (T-amb) and its memory of the temperature of its cultivation (T-cult). The AFD neuron is part of a neural circuit that underlies thermotactic behavior. By monitoring the fluorescence of pH-sensitive green fluorescent protein localized to synaptic vesicles, we measured the rate of the synaptic release of AFD in worms cultivated at temperatures between 15 and 25degreesC, and subjected to fixed, ambient temperatures in the same range. We found that the rate of AFD synaptic release is high if either T-amb > T-cult or T-amb > T-cult, but AFD synaptic release is low if T-amb congruent to T-cult. This suggests that AFD encodes a direct comparison between T-amb and T-cult.

Bommireddy R et al. (2007) Trends Mol Med "TGFbeta1 and Treg cells: alliance for tolerance."

Bommireddy R, Doetschman T

[Trends Mol Med, 2007]

Transforming growth factor beta1 (TGFbeta1), an important pleiotropic, immunoregulatory cytokine, uses distinct signaling mechanisms in lymphocytes to affect T-cell homeostasis, regulatory T (T(reg))-cell and effector-cell function and tumorigenesis. Defects in TGFbeta1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases. TGFbeta1 prevents abnormal T-cell activation through the modulation of Ca(2+)-calcineurin signaling in a Caenorhabditis elegans Sma and Drosophila Mad proteins (SMAD)3 and SMAD4-independent manner; however, in T(reg) cells, its effects are mediated, at least in part, through SMAD signaling. TGFbeta1 also acts as a pro-inflammatory cytokine and induces interleukin (IL)-17-producing pathogenic T-helper cells (T(h) IL-17 cells) synergistically during an inflammatory response in which IL-6 is produced. Here, we will review TGFbeta1 and its signaling in T cells with an emphasis on the regulatory arm of immune tolerance.

Agulnik SI et al. (1995) Genomics "Conservation of the T-box gene family from Mus musculus to Caenorhabditis elegans."

Bollag RJ, Silver LM, Agulnik SI

[Genomics, 1995]

Recently, a novel family of genes with a region of homology to the mouse T locus, which is known to play a crucial, and conserved, role in vertebrate development, has been discovered. The region of homology has been named the T-box. The T-box domain of the prototypical T locus product is associated with sequence-specific DNA binding activity. In this report, we have characterized four members of the T-box gene family from the nematode Caenorhabditis elegans. All lie in close proximity to each other in the middle of chromosome III. Homology analysis among all completely sequenced T-box products indicates a larger size for the conserved T-box domain (166 to 203 residues) than previously reported. Phylogenetic analysis suggests that one C. elegans T-box gene may be a direct ortholog of the mouse Tbx2 and Drosophila omb genes. The accumulated data demonstrate the ancient nature of the T-box gene family and suggest the existence of at least three separate T-box-containing genes in a common early metazoan ancestor to nematodes and vertebrates.

Ju T et al. (2006) Glycobiology "Identification of core 1 O-glycan T-synthase from Caenorhabditis elegans."

Ju T, Zheng Q, Cummings RD

[Glycobiology, 2006]

The common O-glycan core structure in animal glycoproteins is the core 1 disaccharide Galbeta1-3GalNAcalpha1-Ser/Thr, which is generated by addition of Gal to GalNAcalpha1-Ser/Thr by core 1 UDP-Gal:GalNAcalpha1-Ser/Thr beta1,3-galactosyltransferase (core 1 beta3-Gal-T or T-synthase, EC2.4.1.122)(2). Although O-glycans play important roles in vertebrates, much remains to be learned from model organisms such as the free-living nematode Caenorhabditis elegans, which offer many advantages in exploring O-glycan structure/function. Here we report the cloning and enzymatic characterization of T-synthase from C. elegans (Ce-T-synthase). A putative C. elegans gene for T-synthase, C38H2.2, was identified in GenBank by a BlastP search using the human T-synthase protein sequence. The full-length cDNA for Ce-T-synthase, which was generated by PCR using a C. elegans cDNA library as the template, contains 1,170 bp including the stop TAA. The cDNA encodes a protein of 389 amino acids with typical type-II membrane topology and a remarkable 42.7% identity to the human T-synthase. Ce-T-synthase has 7 Cys residues in the lumenal domain including 6 conserved Cys residues in all of the orthologs. The Ce-T-synthase has 4 potential N-glycosylation sequons, whereas the mammalian orthologs lack N-glycosylation sequons. Only one gene for Ce-T-synthase was identified in the genome-wide search and it contains 8 exons. Promoter analysis of the Ce-T-synthase using green fluorescent protein constructs show that the gene is expressed at all developmental stages and appears to be in all cells. Unexpectedly, only minimal activity was recovered in the recombinant, soluble Ce-T-synthase secreted from a wide variety of mammalian cell lines, whereas robust enzyme activity was recovered in the soluble Ce-T-synthase expressed in Hi-5 insect cells. Vertebrate T-synthase requires the molecular chaperone Cosmc, but our results show that Ce-T-synthase does not require Cosmc, and might require invertebrate-specific factors for formation of the optimally active enzyme. These results show that the Ce-T-synthase is a functional ortholog to the human T-synthase in generating core 1 O-glycans and opens new avenues to explore O-glycan function in this model organism.

Muir RE et al. (2007) Int J Syst Evol Microbiol "Leucobacter chromiireducens subsp. solipictus subsp. nov., a pigmented bacterium isolated from the nematode Caenorhabditis elegans, and emended description of L. chromiireducens."

Muir RE, Tan MW

[Int J Syst Evol Microbiol, 2007]

A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming, irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell-wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number of shared biochemical characteristics, strain TAN 31504(T) was placed in the genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG 22506(T) indicating that these two strains belong to the same species, when the recommended threshold value of 70 % DNA-DNA relatedness for the definition of a bacterial species by the ad hoc committee on reconciliation of approaches to bacterial systematics is considered. Based on distinct differences in morphology, physiology, chemotaxonomic markers and various biochemical characteristics, it is proposed to split the species L. chromiireducens into two novel subspecies, Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L-1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp. solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).