scholarly journals Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditis elegans

2021 ◽  
Author(s):  
Chayki Charar ◽  
Sally Metsuyanim-Cohen ◽  
Daniel Z. Bar
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Life Span ◽  
Dietary Restriction ◽  
Metabolic Regulation ◽  
Fat Content ◽  
Mtor Pathway ◽  
Reduced Body ◽  
Animal Size ◽  
Mtor Complex 1

Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.

scholarly journals Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditis elegans

2020 ◽  
Author(s):  
Chayki Charar ◽  
Sally Metsuyanim-Cohen ◽  
Yosef Gruenbaum ◽  
Daniel Z Bar
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Life Span ◽  
Dietary Restriction ◽  
Metabolic Regulation ◽  
Fat Content ◽  
Mtor Pathway ◽  
Reduced Body ◽  
Animal Size ◽  
Mtor Complex 1

AbstractAnimals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.

scholarly journals Cell size and fat content of dietary-restricted Caenorhabditis elegans are regulated by ATX-2, an mTOR repressor

2016 ◽  
Vol 113 (32) ◽  
pp. E4620-E4629 ◽  
Author(s):  
Daniel Z. Bar ◽  
Chayki Charar ◽  
Jehudith Dorfman ◽  
Tam Yadid ◽  
Lionel Tafforeau ◽  
...  
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Cell Size ◽  
Fat Content ◽  
Mtor Pathway ◽  
The Body ◽  
Dependent Growth ◽  
Multiple Species ◽  
Amp Activated Protein Kinase ◽  
Gdp Dissociation Inhibitor

Dietary restriction (DR) is a metabolic intervention that extends the lifespan of multiple species, including yeast, flies, nematodes, rodents, and, arguably, rhesus monkeys and humans. Hallmarks of lifelong DR are reductions in body size, fecundity, and fat accumulation, as well as slower development. We have identified atx-2, the Caenorhabditis elegans homolog of the human ATXN2L and ATXN2 genes, as the regulator of these multiple DR phenotypes. Down-regulation of atx-2 increases the body size, cell size, and fat content of dietary-restricted animals and speeds animal development, whereas overexpression of atx-2 is sufficient to reduce the body size and brood size of wild-type animals. atx-2 regulates the mechanistic target of rapamycin (mTOR) pathway, downstream of AMP-activated protein kinase (AMPK) and upstream of ribosomal protein S6 kinase and mTOR complex 1 (TORC1), by its direct association with Rab GDP dissociation inhibitor β, which likely regulates RHEB shuttling between GDP-bound and GTP-bound forms. Taken together, this work identifies a previously unknown mechanism regulating multiple aspects of DR, as well as unknown regulators of the mTOR pathway. They also extend our understanding of diet-dependent growth retardation, and offers a potential mechanism to treat obesity.

scholarly journals Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans

2004 ◽  
Vol 379 (1) ◽  
pp. 191-198 ◽  
Author(s):  
You-Jun FEI ◽  
Jin-Cai LIU ◽  
Katsuhisa INOUE ◽  
Lina ZHUANG ◽  
Katsuya MIYAKE ◽  
...  
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Life Span ◽  
Critical Role ◽  
Fat Content ◽  
Metabolic Energy ◽  
Coupled Transport ◽  
C Elegans ◽  
Citrate Transporter ◽  
Inward Currents

We have cloned and functionally characterized an Na+-coupled citrate transporter from Caenorhabditis elegans (ceNAC-2). This transporter shows significant sequence homology to Drosophila Indy and the mammalian Na+-coupled citrate transporter NaCT (now known as NaC2). When heterologously expressed in a mammalian cell line or in Xenopus oocytes, the cloned ceNAC-2 mediates the Na+-coupled transport of various intermediates of the citric acid cycle. However, it transports the tricarboxylate citrate more efficiently than dicarboxylates such as succinate, a feature different from that of ceNAC-1 (formerly known as ceNaDC1) and ceNAC-3 (formerly known as ceNaDC2). The transport process is electrogenic, as evidenced from the substrate-induced inward currents in oocytes expressing the transporter under voltage-clamp conditions. Expression studies using a reporter-gene fusion method in transgenic C. elegans show that the gene is expressed in the intestinal tract, the organ responsible for not only the digestion and absorption of nutrients but also for the storage of energy in this organism. Functional knockdown of the transporter by RNAi (RNA interference) not only leads to a significant increase in life span, but also causes a significant decrease in body size and fat content. The substrates of ceNAC-2 play a critical role in metabolic energy production and in the biosynthesis of cholesterol and fatty acids. The present studies suggest that the knockdown of these metabolic functions by RNAi is linked to an extension of life span and a decrease in fat content and body size.

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 Paternal dietary restriction affects progeny fat content in Caenorhabditis elegans

IUBMB Life ◽  
2012 ◽  
Vol 64 (7) ◽  
pp. 644-648 ◽  
Author(s):  
Claudia Miersch ◽  
Frank Döring
Keyword(s):  
Caenorhabditis Elegans ◽  
Dietary Restriction ◽  
Fat Content

scholarly journals Killed Bifidobacterium longum enhanced stress tolerance and prolonged life span of Caenorhabditis elegans via DAF-16

2018 ◽  
Vol 120 (8) ◽  
pp. 872-880 ◽  
Author(s):  
Takaya Sugawara ◽  
Kazuichi Sakamoto
Keyword(s):  
Caenorhabditis Elegans ◽  
Life Span ◽  
Stress Tolerance ◽  
Bifidobacterium Longum ◽  
Intestinal Flora ◽  
Dependent Manner ◽  
Physiological Effects ◽  
E Coli ◽  
C Elegans ◽  
Reduced Body

AbstractProbiotics are bacteria among the intestinal flora that are beneficial for human health. Bifidobacterium longum (BL) is a prototypical probiotic that is widely used in yogurt making, supplements and others. Although various physiological effects of BL have been reported, those associated with longevity and anti-ageing still remain elusive. Here we aimed to elucidate the physiological effects of killed BL (BR-108) on stress tolerance and longevity of Caenorhabditis elegans and their mechanisms. Worms fed killed BL in addition to Escherichia coli (OP50) displayed reduced body length in a BL dose-dependent manner. When compared with those fed E. coli alone, these worms had a higher survival rate following heat stress at 35°C and hydrogen peroxide-induced oxidative stress. A general decrease in motility was observed over time in all worms; however, killed BL-fed ageing worms displayed increased movement and longer life span than those fed E. coli alone. However, the longevity effect was suppressed in sir-2.1, daf-16 and skn-1-deficient worms. Killed BL induced DAF-16 nuclear localisation and increased the expression of the DAF-16 target gene hsp-12.6. These results revealed that the physiological effects of killed BL in C. elegans were mediated by DAF-16 activation. These findings contradict previous observations with different Bifidobacterium and Lactobacillus strains, which showed the role for SKN-1 independently of DAF-16.

scholarly journals Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans

2008 ◽  
Vol 8 (1) ◽  
Author(s):  
Erica D Smith ◽  
Tammi L Kaeberlein ◽  
Brynn T Lydum ◽  
Jennifer Sager ◽  
K Linnea Welton ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Life Span ◽  
Dietary Restriction ◽  
Life Span Extension ◽  
Independent Life

A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Y. Suzuki ◽  
M.D. Yandell ◽  
P.J. Roy ◽  
S. Krishna ◽  
C. Savage-Dunn ◽  
...  
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Expression Pattern ◽  
Genetic Interactions ◽  
Loss Of Function ◽  
Male Tail ◽  
C Elegans ◽  
Reduced Body ◽  
Smad Signaling Pathway ◽  
Dose Dependent

We cloned the dbl-1 gene, a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes. Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures. Conversely, dbl-1 overexpression causes markedly increased body size and partly complementary male tail phenotypes, indicating that DBL-1 acts as a dose-dependent regulator of these processes. Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway, for which DBL-1 is a previously unidentified ligand. Our study of the dbl-1 expression pattern suggests a role for neuronal cells in global size regulation as well as male tail patterning.

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