scholarly journals The genetic paradigms of dietary restriction fail to extend life span in cep-1(gk138) mutant of C. elegans p53 due to possible background mutations

2020 ◽  
Author(s):  
Anita Goyala ◽  
Aiswarya Baruah ◽  
Arnab Mukhopadhyay
Keyword(s):  
Life Span ◽  
Dietary Restriction ◽  
Model Systems ◽  
Regulation Of Expression ◽  
Life Span Extension ◽  
Phenotypic Differences ◽  
C Elegans ◽  
Xenobiotic Detoxification ◽  
Organismal Biology ◽  
Extend Life Span

AbstractDietary restriction (DR) increases life span and improves health in most model systems tested, including non-human primates. In C. elegans, as in other models, DR leads to reprogramming of metabolism, improvements in mitochondrial health, large changes in gene expression, including increase in expression of cytoprotective genes, better proteostasis etc. Understandably, multiple global transcriptional regulators like transcription factors FOXO/DAF-16, FOXA/PHA-4, HSF1/HSF-1 and NRF2/SKN-1 are important for DR longevity. Considering the wide-ranging effects of p53 on organismal biology, we asked whether the C. elegans ortholog, CEP-1 is required for DR-mediated longevity assurance. We employed the widely-used TJ1 strain of cep-1(gk138). We show that cep-1(gk138) suppresses the life span extension of two genetic paradigms of DR, but two non-genetic modes of DR remain unaffected in this strain. We find that in cep-1(gk138), two aspects of DR, increased autophagy and the up-regulation of expression of cytoprotective xenobiotic detoxification program (cXDP) genes are dampened. Importantly, we find that background mutation(s) in the strain may be the actual cause for the phenotypic differences that we observed and cep-1 may not be directly involved in genetic DR-mediated longevity assurance in worms. Identifying these mutation(s) may reveal a novel regulator of longevity required specifically by genetic modes of DR.

scholarly journals The genetic paradigms of dietary restriction fail to extend life span in cep-1(gk138) mutant of C. elegans p53 due to possible background mutations

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241478
Author(s):  
Anita Goyala ◽  
Aiswarya Baruah ◽  
Arnab Mukhopadhyay
Keyword(s):  
Life Span ◽  
Dietary Restriction ◽  
Transcriptional Regulators ◽  
Model Systems ◽  
Life Span Extension ◽  
Phenotypic Differences ◽  
C Elegans ◽  
Xenobiotic Detoxification ◽  
Organismal Biology ◽  
Extend Life Span

Dietary restriction (DR) increases life span and improves health in most model systems tested, including non-human primates. In C. elegans, as in other models, DR leads to reprogramming of metabolism, improvements in mitochondrial health, large changes in expression of cytoprotective genes and better proteostasis. Understandably, multiple global transcriptional regulators like transcription factors FOXO/DAF-16, FOXA/PHA-4, HSF1/HSF-1 and NRF2/SKN-1 are important for DR longevity. Considering the wide-ranging effects of p53 on organismal biology, we asked whether the C. elegans ortholog, CEP-1 is required for DR-mediated longevity assurance. We employed the widely-used TJ1 strain of cep-1(gk138). We show that cep-1(gk138) suppresses the life span extension of two genetic paradigms of DR, but two non-genetic modes of DR remain unaffected in this strain. We find that two aspects of DR, increased autophagy and up-regulation of the expression of cytoprotective xenobiotic detoxification program (cXDP) genes, are dampened in cep-1(gk138). Importantly, we find that background mutation(s) in the strain may be the actual cause for the phenotypic differences that we observed and cep-1 may not be directly involved in genetic DR-mediated longevity assurance in worms. Identifying these mutation(s) may reveal a novel regulator of longevity required specifically by genetic modes of DR.

scholarly journals Life‐span extension by dietary restriction is mediated by NLP‐7 signaling and coelomocyte endocytosis in C. elegans

2009 ◽  
Vol 24 (2) ◽  
pp. 383-392 ◽  
Author(s):  
Sang‐Kyu Park ◽  
Christopher D. Link ◽  
Thomas E. Johnson
Keyword(s):  
Life Span ◽  
Dietary Restriction ◽  
Life Span Extension ◽  
C Elegans

scholarly journals CBP-1 Acts in GABAergic Neurons to Double Life Span in Axenically Cultured Caenorhabditis elegans

2017 ◽  
Vol 74 (8) ◽  
pp. 1198-1205 ◽  
Author(s):  
Huaihan Cai ◽  
Ineke Dhondt ◽  
Lieselot Vandemeulebroucke ◽  
Caroline Vlaeminck ◽  
Madina Rasulova ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Life Span ◽  
Dietary Restriction ◽  
Gabaergic Neurons ◽  
Creb Binding Protein ◽  
Axenic Medium ◽  
Life Span Extension ◽  
Gene Functions ◽  
Key Genes

Abstract When cultured in axenic medium, Caenorhabditis elegans shows the largest life-span extension compared with other dietary restriction regimens. However, the underlying molecular mechanism still remains elusive. The gene cbp-1, encoding the worm ortholog of p300/CBP (CREB-binding protein), is one of the very few key genes known to be essential for life span doubling under axenic dietary restriction (ADR). By using tissue-specific RNAi, we found that cbp-1 expression in the germline is essential for fertility, whereas this gene functions specifically in the GABAergic neurons to support the full life span–doubling effect of ADR. Surprisingly, GABA itself is not required for ADR-induced longevity, suggesting a role of neuropeptide signaling. In addition, chemotaxis assays illustrate that neuronal inactivation of CBP-1 affects the animals’ food sensing behavior. Together, our results show that the strong life-span extension in axenic medium is under strict control of GABAergic neurons and may be linked to food sensing.

scholarly journals Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

2016 ◽  
Vol 113 (40) ◽  
pp. 11277-11282 ◽  
Author(s):  
Jason G. Wood ◽  
Brian C. Jones ◽  
Nan Jiang ◽  
Chengyi Chang ◽  
Suzanne Hosier ◽  
...  
Keyword(s):  
Life Span ◽  
Dietary Restriction ◽  
Fat Body ◽  
Transcriptase Inhibitor ◽  
Dna Double Strand Breaks ◽  
Expression Of Genes ◽  
Age Related ◽  
Extend Life Span ◽  
Genetic Interventions ◽  
Heterochromatin Structure

Transposable elements (TEs) are mobile genetic elements, highly enriched in heterochromatin, that constitute a large percentage of the DNA content of eukaryotic genomes. Aging in Drosophila melanogaster is characterized by loss of repressive heterochromatin structure and loss of silencing of reporter genes in constitutive heterochromatin regions. Using next-generation sequencing, we found that transcripts of many genes native to heterochromatic regions and TEs increased with age in fly heads and fat bodies. A dietary restriction regimen, known to extend life span, repressed the age-related increased expression of genes located in heterochromatin, as well as TEs. We also observed a corresponding age-associated increase in TE transposition in fly fat body cells that was delayed by dietary restriction. Furthermore, we found that manipulating genes known to affect heterochromatin structure, including overexpression of Sir2, Su(var)3–9, and Dicer-2, as well as decreased expression of Adar, mitigated age-related increases in expression of TEs. Increasing expression of either Su(var)3–9 or Dicer-2 also led to an increase in life span. Mutation of Dicer-2 led to an increase in DNA double-strand breaks. Treatment with the reverse transcriptase inhibitor 3TC resulted in decreased TE transposition as well as increased life span in TE-sensitized Dicer-2 mutants. Together, these data support the retrotransposon theory of aging, which hypothesizes that epigenetically silenced TEs become deleteriously activated as cellular defense and surveillance mechanisms break down with age. Furthermore, interventions that maintain repressive heterochromatin and preserve TE silencing may prove key to preventing damage caused by TE activation and extending healthy life span.

scholarly journals Life Span Extension via eIF4G Inhibition Is Mediated by Posttranscriptional Remodeling of Stress Response Gene Expression in C. elegans

2011 ◽  
Vol 14 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Aric N. Rogers ◽  
Di Chen ◽  
Gawain McColl ◽  
Gregg Czerwieniec ◽  
Krysta Felkey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Life Span ◽  
Response Gene ◽  
Life Span Extension ◽  
C Elegans ◽  
Stress Response Gene

scholarly journals UPRER promotes lipophagy independent of chaperones to extend life span

2020 ◽  
Vol 6 (1) ◽  
pp. eaaz1441 ◽  
Author(s):  
Joseph R. Daniele ◽  
Ryo Higuchi-Sanabria ◽  
Jenni Durieux ◽  
Samira Monshietehadi ◽  
Vidhya Ramachandran ◽  
...  
Keyword(s):  
Life Span ◽  
Genetic Factors ◽  
Protein Homeostasis ◽  
Life Span Extension ◽  
Unfolded Protein ◽  
Extend Life Span ◽  
Protein Chaperones ◽  
Ectopic Activation ◽  
The Unfolded Protein Response ◽  
Protein Response

Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPRER) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span. Here, we find that this activation not only promotes chaperones but also facilitates ER restructuring and ER function. This restructuring is concomitant with lipid depletion through lipophagy. Activation of lipophagy is distinct from chaperone induction and is required for the life-span extension found in this paradigm. Last, we find that overexpression of the lipophagy component, ehbp-1, is sufficient to deplete lipids, remodel ER, and promote life span. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the proteostasis arm through protein chaperones and metabolic changes through lipid depletion mediated by EH domain binding protein 1 (EHBP-1).

scholarly journals Lack of Peroxisomal Catalase Causes a Progeric Phenotype inCaenorhabditis elegans

2004 ◽  
Vol 279 (19) ◽  
pp. 19996-20001 ◽  
Author(s):  
Oleh I. Petriv ◽  
Richard A. Rachubinski
Keyword(s):  
Life Span ◽  
Aging Process ◽  
Target Genes ◽  
Egg Laying ◽  
C Elegans ◽  
Extend Life Span ◽  
Genes Encoding ◽  
Shorten Life Span ◽  
Development And Aging ◽  
Genetic Mutants

Studies using the nematodeCaenorhabditis elegansas a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling pathway in the regulation of organismal longevity through its action on a subset of target genes. These targets can be classified into genes that shorten or extend life-span upon their induction. Genes that shorten life-span include a variety of stress response genes, among them genes encoding catalases; however, no evidence directly implicates catalases in the aging process of nematodes or other organisms. Using genetic mutants, we show that lack of peroxisomal catalase CTL-2 causes a progeric phenotype inC. elegans. Lack of peroxisomal catalase also affects the developmental program ofC. elegans, since Δctl-2mutants exhibit decreased egg laying capacity. In contrast, lack of cytosolic catalase CTL-1 has no effect on either nematode aging or egg laying capacity. The Δctl-2mutation also shortens the maximum life-span of the long lived Δclk-1mutant and accelerates the onset of its egg laying period. The more rapid aging of Δctl-2worms is apparently not due to increased carbonylation of the majorC. elegansproteins, although altered peroxisome morphology in the Δctl-2mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Δctl-2mutant. Our findings support an important role for peroxisomal catalase in both the development and aging ofC. elegansand suggest the utility of the Δctl-2mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia.

Sign in / Sign up

Export Citation Format

Share Document