Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

Pyruvate imbalance mediates metabolic reprogramming and mimics lifespan extension by dietary restriction in Caenorhabditis elegans

Aging Cell ◽

10.1111/j.1474-9726.2010.00640.x ◽

2010 ◽

Vol 10 (1) ◽

pp. 39-54 ◽

Cited By ~ 52

Author(s):

Laurent Mouchiroud ◽

Laurent Molin ◽

Prasad Kasturi ◽

Mohamed N. Triba ◽

Marc Emmanuel Dumas ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Dietary Restriction ◽

Metabolic Reprogramming ◽

Lifespan Extension

Acanthopanax sessiliflorus stem confers increased resistance to environmental stresses and lifespan extension in Caenorhabditis elegans

New Biotechnology ◽

10.1016/j.nbt.2014.05.973 ◽

2014 ◽

Vol 31 ◽

pp. S203-S204

Author(s):

Sang-Kyu Park ◽

Jin-Kook Park ◽

Chul-Kyu Kim ◽

Sang-Ki Kong ◽

A-Reum Yu ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Environmental Stresses ◽

Lifespan Extension ◽

Acanthopanax Sessiliflorus

Lifespan Extension of Caenorhabditis elegans by Butyricicoccus pullicaecorum and Megasphaera elsdenii with Probiotic Potential

Current Microbiology ◽

10.1007/s00284-017-1416-6 ◽

2017 ◽

Vol 75 (5) ◽

pp. 557-564 ◽

Cited By ~ 7

Author(s):

Gayeung Kwon ◽

Jiyun Lee ◽

Jong-Ho Koh ◽

Young-Hee Lim

Keyword(s):

Caenorhabditis Elegans ◽

Lifespan Extension ◽

Probiotic Potential ◽

Megasphaera Elsdenii

Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2021.0701 ◽

2021 ◽

Vol 288 (1950) ◽

Author(s):

Edward R. Ivimey-Cook ◽

Kris Sales ◽

Hanne Carlsson ◽

Simone Immler ◽

Tracey Chapman ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Dietary Restriction ◽

Mortality Risk ◽

Lifespan Extension ◽

Dietary Interventions ◽

Negative Effects ◽

Trade Offs ◽

Wide Range ◽

Broad Variety

Dietary restriction (DR) increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here, we investigated the effect of DR by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in Caenorhabditis elegans . We show that while TF robustly reduces mortality risk and improves late-life reproduction of the individuals subject to TF (P 0 ), it has a wide range of both positive and negative effects on their descendants (F 1 –F 3 ). Remarkably, great-grandparental exposure to TF in early life reduces fitness and increases mortality risk of F 3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of DR, underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

Piceatannol, a Natural Stilbene, Extends the Lifespan of Caenorhabditis elegans Under Fasting Through Inhibition of Lipolysis

Current Developments in Nutrition ◽

10.1093/cdn/nzaa040_038 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 38-38

Author(s):

Jang Miran ◽

Zhang Yuan ◽

Bai Juan ◽

Jun-Bae An ◽

Park Yeonhwa ◽

...

Keyword(s):

Lipid Metabolism ◽

Caenorhabditis Elegans ◽

Negative Energy ◽

Hormone Sensitive Lipase ◽

Pcr Analysis ◽

Lifespan Extension ◽

Mrna Levels ◽

Free Glycerol ◽

C Elegans ◽

Glycerol Level

Abstract Objectives Lipolysis is the catabolic process that hydrolyzes triglyceride (TG) to free fatty acids (FFAs) and glycerol under negative energy balance such as fasting. In adipocytes, adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase play key roles in a series of TG hydrolysis reactions in mammals. However, overly activated adipose lipolysis is believed to contribute to link between obesity and systemic inflammation and oxidative stress. We previously demonstrated that piceatannol (PIC), a natural resveratrol analogue, inhibits adipogenesis in cultured adipocytes and lipogenesis in Caenorhabditis elegans. Furthermore, we showed that PIC extends the lifespan of C. elegans via the insulin/IGF-1 signaling. However, the effects of PIC on lipid metabolism during fasting state is unknown. Methods We conducted Oil-Red-O assay, Enzyme assay (TG and Free glycerol contents), PCR analysis and lifespan assay. Results In this study, we demonstrated that PIC-treated C. elegans exhibited suppressed lipolysis under fasting as judged by increased lipid accumulation and TG levels with decreased free glycerol level. Consistent with these findings, PIC treatment resulted in decreased mRNA levels of genes involved lipolysis such as atgl-1, hosl-1 and aak-2 in fasted C. elegans. Also, PIC treatment augmented fasting-induced lifespan of C. elegans by an increased daf-16 gene expression. However, such effect was abolished when atgl-1, aak-2, and daf-16 mutants were treated with PIC. In addition, we also found that autophagy is required for PIC-induced lifespan in C. elegans during fasting since autophagy inhibitor treatments and autophagy gene deficient worms resulted in blunting the lifespan extension effect of PIC. Conclusions Collectively, our results indicate that PIC contributes to lifespan extension in C. elegans during fasting possibly through regulating lipolysis- and/or autophagy-dependent lipid metabolism. Funding Sources 1. The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2019R1A2C1086146) and (2019R1A6A3A03033878) 2. The Rural Development Administration of the Republic of Korea.

The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2011.02.079 ◽

2011 ◽

Vol 406 (3) ◽

pp. 478-482 ◽

Cited By ~ 22

Author(s):

Juan Carlos Fierro-González ◽

María González-Barrios ◽

Antonio Miranda-Vizuete ◽

Peter Swoboda

Keyword(s):

Caenorhabditis Elegans ◽

Dietary Restriction ◽

Lifespan Extension ◽

Adult Lifespan

JAMP Optimizes ERAD to Protect Cells from Unfolded Proteins

Molecular Biology of the Cell ◽

10.1091/mbc.e08-08-0839 ◽

2008 ◽

Vol 19 (11) ◽

pp. 5019-5028 ◽

Cited By ~ 9

Author(s):

Marianna Tcherpakov ◽

Limor Broday ◽

Agnes Delaunay ◽

Takayuki Kadoya ◽

Ashwani Khurana ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Er Stress ◽

Transmembrane Protein ◽

26S Proteasome ◽

Misfolded Proteins ◽

Unfolded Proteins ◽

Cellular Homeostasis ◽

Channel Proteins ◽

Proteasome Subunits ◽

Opposite Response

Clearance of misfolded proteins from the ER is central for maintenance of cellular homeostasis. This process requires coordinated recognition, ER-cytosol translocation, and finally ubiquitination-dependent proteasomal degradation. Here, we identify an ER resident seven-transmembrane protein (JAMP) that links ER chaperones, channel proteins, ubiquitin ligases, and 26S proteasome subunits, thereby optimizing degradation of misfolded proteins. Elevated JAMP expression promotes localization of proteasomes at the ER, with a concomitant effect on degradation of specific ER-resident misfolded proteins, whereas inhibiting JAMP promotes the opposite response. Correspondingly, a jamp-1 deleted Caenorhabditis elegans strain exhibits hypersensitivity to ER stress and increased UPR. Using biochemical and genetic approaches, we identify JAMP as important component for coordinated clearance of misfolded proteins from the ER.

Lifespan extension in Caenorhabditis elegans by oxyresveratrol supplementation in hyper-branched cyclodextrin-based nanosponges

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2020.119862 ◽

2020 ◽

Vol 589 ◽

pp. 119862 ◽

Cited By ~ 1

Author(s):

Adrián Matencio ◽

M. Alejandra Guerrero-Rubio ◽

Fabrizio Caldera ◽

Claudio Cecone ◽

Francesco Trotta ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Lifespan Extension