- NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair.
Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD+, and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD+ reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD+ also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions.
- PHA-4 organogenesis
The
pha-4 locus encodes a forkhead box A (FoxA/HNF3) transcription factor homolog that specifies organ identity for Caenorhabditis elegans pharyngeal cells. We used microarrays to identify pharyngeal genes and analyzed those genes to determine which were direct PHA-4 targets. Our data suggest that PHA-4 directly activates most or all pharyngeal genes. Furthermore, the relative affinity of PHA-4 for different TRTTKRY (R = A/G, K = T/G, Y = T/C) elements modulates the onset of gene expression, providing a mechanism to activate pharyngeal genes at different developmental stages. We suggest that direct transcriptional regulation of entire gene networks may be a common feature of organ identity genes. A genotyping experiment design type classifies an individual or group of individuals on the basis of alleles, haplotypes, SNP's. Keywords: genotyping_design
- PQM-1 controls hypoxic survival via regulation of lipid metabolism.
Worms were exposed to 5 mM CoCl2 at the early day 1 of adulthood stage for 6 hr and 20 hr. Untreated worms were used as controls. Worms were collected, RNA isolated and hybridized on 4x44K C. elegans arrays (Agilent) at 60C overnight, as previously described 1). Three biological replicates were used. Significant differentially-expressed gene sets were identified using one or two-class SAM 2). 1) Shaw, W. M., Luo, S., Landis, J., Ashraf, J. & Murphy, C. T. The C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling. Curr Biol 17, 1635-1645, doi:10.1016/j.cub.2007.08.058 (2007). 2) Tusher, V. G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98, 5116-5121, doi:10.1073/pnas.091062498 (2001).
- Simplification and desexualization of gene expression in self-fertile nematodes.
This project defines the transcriptomes of XO (male) and XX (female or mutant pseudo-female) Caenorhabditis nematodes. The data allow the overall composition and sexual regulation of the transcriptome within a single species to be determined. In addition, the five related species studied allow meta-comparisons between them. Because two of the five (C. elegans and C. briggsae) produce a self-fertile XX hermaphrodite, while the XX sex in the remaining three (C. japonica, C. remanei, and C. brenneri) are true females, the data are particularly useful for inferring effects of sexual mode on genome-wide gene expression. Overall Design: L4 larvae and adults were pooled for each sex for five species (C. elegans, C. briggsae, C. japonica, C. brenneri, and C. remanei). Each of these 10 species-sex combinations was replicated three times, for a total of 30 samples.
- Simplification and desexualization of gene expression in self-fertile nematodes.
This project defines the transcriptomes of XO (male) and XX (female or mutant pseudo-female) Caenorhabditis nematodes. The data allow the overall composition and sexual regulation of the transcriptome within a single species to be determined. In addition, the five related species studied allow meta-comparisons between them. Because two of the five (C. elegans and C. briggsae) produce a self-fertile XX hermaphrodite, while the XX sex in the remaining three (C. japonica, C. remanei, and C. brenneri) are true females, the data are particularly useful for inferring effects of sexual mode on genome-wide gene expression. Overall Design: L4 larvae and adults were pooled for each sex for five species (C. elegans, C. briggsae, C. japonica, C. brenneri, and C. remanei). Each of these 10 species-sex combinations was replicated three times, for a total of 30 samples.
- Simplification and desexualization of gene expression in self-fertile nematodes.
This project defines the transcriptomes of XO (male) and XX (female or mutant pseudo-female) Caenorhabditis nematodes. The data allow the overall composition and sexual regulation of the transcriptome within a single species to be determined. In addition, the five related species studied allow meta-comparisons between them. Because two of the five (C. elegans and C. briggsae) produce a self-fertile XX hermaphrodite, while the XX sex in the remaining three (C. japonica, C. remanei, and C. brenneri) are true females, the data are particularly useful for inferring effects of sexual mode on genome-wide gene expression. Overall Design: L4 larvae and adults were pooled for each sex for five species (C. elegans, C. briggsae, C. japonica, C. brenneri, and C. remanei). Each of these 10 species-sex combinations was replicated three times, for a total of 30 samples.
- Simplification and desexualization of gene expression in self-fertile nematodes.
This project defines the transcriptomes of XO (male) and XX (female or mutant pseudo-female) Caenorhabditis nematodes. The data allow the overall composition and sexual regulation of the transcriptome within a single species to be determined. In addition, the five related species studied allow meta-comparisons between them. Because two of the five (C. elegans and C. briggsae) produce a self-fertile XX hermaphrodite, while the XX sex in the remaining three (C. japonica, C. remanei, and C. brenneri) are true females, the data are particularly useful for inferring effects of sexual mode on genome-wide gene expression. Overall Design: L4 larvae and adults were pooled for each sex for five species (C. elegans, C. briggsae, C. japonica, C. brenneri, and C. remanei). Each of these 10 species-sex combinations was replicated three times, for a total of 30 samples.