In JoVE (1)

Other Publications (4)

Articles by Francis R. G. Amrit in JoVE

Other articles by Francis R. G. Amrit on PubMed

Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

PloS One. Apr, 2010  |  Pubmed ID: 20369008

Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin-like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species.

Younger for Longer: Insulin Signalling, Immunity and Ageing

Current Aging Science. Dec, 2010  |  Pubmed ID: 20735349

Genes, the environment and stochastic factors such as lifestyle are major contributors to the universally shared phenomenon of ageing. It is now clear that these different inputs act through evolutionarily conserved pathways to regulate lifespan in a wide range of animals. Among several such pathways, the IIS [Insulin/IGF (Insulin -like growth factor)- like signalling] pathway, initially identified in the roundworm, Caenorhabditis elegans, is the most significant modulator of ageing. Consisting of a PI 3 kinase-signalling cascade downstream of a transmembrane insulin-like growth factor receptor, this pathway ultimately regulates the activity of a transcription factor with a huge repertoire of transcriptional outputs. The effect of this is that the IIS pathway co-ordinately controls several processes, including immunity and stress resistance,which in tandem seem to regulate longevity. Since both the function and molecular architecture of the IIS pathway is conserved from yeast to mammals, this coordinate regulation appears to be a general feature of the ageing processes in animals. Here we review the evolutionary conservation of the IIS pathway and discuss this in relation to recent findings on the molecular basis of ageing. We also reflect on the impact and significance of the evolutionary diversification of this pathway and propose a model for how such differences could explain both inter and intra-species differences in ageing.

Germline Signals Deploy NHR-49 to Modulate Fatty-acid β-oxidation and Desaturation in Somatic Tissues of C. Elegans

PLoS Genetics. Dec, 2014  |  Pubmed ID: 25474470

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity.

X Chromosome Crossover Formation and Genome Stability in Caenorhabditis Elegans Are Independently Regulated by Xnd-1

G3 (Bethesda, Md.). Dec, 2016  |  Pubmed ID: 27678523

The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs, and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover (CO) distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understood. We have used the xnd-1 mutant of Caenorhabditis elegans to explore the relationship between genome integrity and crossover formation. Known for its role in ensuring X chromosome CO formation and germ line development, we show that xnd-1 also regulates genome stability. xnd-1 mutants exhibited a mortal germ line, high embryonic lethality, high incidence of males, and sensitivity to ionizing radiation. We discovered that a hypomorphic allele of mys-1 suppressed these genome instability phenotypes of xnd-1, but did not suppress the CO defects, suggesting it serves as a separation-of-function allele. mys-1 encodes a histone acetyltransferase, whose homolog Tip60 acetylates H2AK5, a histone mark associated with transcriptional activation that is increased in xnd-1 mutant germ lines, raising the possibility that thresholds of H2AK5ac may differentially influence distinct germ line repair events. We also show that xnd-1 regulated him-5 transcriptionally, independently of mys-1, and that ectopic expression of him-5 suppressed the CO defects of xnd-1 Our work provides xnd-1 as a model in which to study the link between chromatin factors, gene expression, and genome stability.

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