Article
Cell Biology
Shi Quan Wong, Catherine J. Ryan, Dennis M. Bonal, Joslyn Mills, Louis R. Lapierre
Summary: Neuronal TFEB plays an important role in stress resistance and longevity regulation. Its rescue improves heat stress resistance in wildtype animals but not daf-2 mutants. Neuronal TFEB modulates neurotransmission through the uncharacterized protein W06A11.1, inducing peripheral mitochondrial fragmentation and enhancing organismal heat stress resistance.
Article
Cell Biology
Chiao-Yin Lim, Huan-Ting Lin, Caroline Kumsta, Tzu-Chiao Lu, Feng-Yung Wang, Yun-Hsuan Kang, Malene Hansen, Tsui-Ting Ching, Ao-Lin Hsu
Summary: This study reveals that dietary restriction and SAMS-1 repress the activity of SET-2 by limiting the availability of SAM, leading to reduced H3K4me3 levels. As a result, HLH-30/TFEB and PHA-4/FOXA transcription factors are upregulated, promoting the expression of autophagy-related genes and affecting the lifespan of animals.
Article
Biology
Khursheed A. Wani, Debanjan Goswamy, Stefan Taubert, Ramesh Ratnappan, Arjumand Ghazi, Javier E. Irazoqui
Summary: The model organism Caenorhabditis elegans mounts infection-specific transcriptional defense responses against Staphylococcus aureus, which are mainly regulated by hlh-30/TFEB. The study identified FMOs as important innate immunity effectors in animals, specifically the first FMO with innate immunity functions, and revealed the mechanism of FMO regulation through NHR-49/PPAR-alpha during S. aureus infection.
Article
Cell Biology
Miroslav Dinic, Marija Herholz, Uros Kacarevic, Dusan Radojevic, Katarina Novovic, Jelena Dokic, Aleksandra Trifunovic, Natasa Golic
Summary: This study demonstrates that heat-inactivated human commensal Lactobacillus can extend the lifespan of Caenorhabditis elegans and improve age-related physiological features by promoting HLH-30/TFEB-dependent autophagy to delay aging.
Article
Clinical Neurology
Yasmin Fardghassemi, Claudia Maios, J. Alex Parker
Summary: This study conducted a drug screen for SCA3 and identified five small molecule compounds that can restore motor deficiencies, protect against neurodegeneration, and increase the lifespan of worms carrying the ATXN3-CAG89 mutation. Three of these compounds act as modulators for TFEB/HLH-30, a key transcriptional regulator of the autophagy process, and require this gene for their neuroprotective activities.
Article
Biology
Javier Huayta, Joseph P. Crapster, Adriana San-Miguel
Summary: Dietary restriction (DR) activates the DAF-16 transcription factor in C. elegans, leading to lifespan extension. However, the extent of this activation and its impact on lifespan has not been quantitatively determined. In this study, we used CRISPR/Cas9-enabled fluorescent tagging, quantitative image analysis, and machine learning to assess the endogenous activity of DAF-16 under different DR regimes. Our results show strong endogenous DAF-16 activity induced by DR, with the activity being less responsive in aged individuals. DAF-16 activity is a robust predictor of lifespan, accounting for 78% of its variability under DR.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jose A. Martina, David Guerrero-Gomez, Eva Gomez-Orte, Jose Antonio Barcena, Juan Cabello, Antonio Miranda-Vizuete, Rosa Puertollano
Summary: Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH-30, are regulated by a novel mechanism involving cysteine-mediated redox switch under stress conditions, leading to oligomer formation and increased stability to stress. Cysteine oxidation acts as a molecular switch linking redox balance changes with expression of target genes.
Article
Biochemical Research Methods
Natasha Oswal, Olivier M. F. Martin, Sofia Stroustrup, Monika Anna Matusiak Bruckner, Nicholas Stroustrup
Summary: This study reveals the close relationship between vigorous movement cessation (VMC) and lifespan, with the timing of VMC inversely correlated with remaining lifespan. Through measurement and modeling, the researchers show that vigorous movement and lifespan are determined by the interplay of at least two distinct physical declines.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Genetics & Heredity
Chia-En Tsai, Fang-Jung Yang, Ching-Han Lee, Yen-Ping Hsueh, Cheng-Ju Kuo, Chang-Shi Chen
Summary: The study found that the hlh-30 gene plays a key role in combating EHEC infection in C. elegans, while mutants of the unc-89 gene showed increased resistance to EHEC.
Article
Food Science & Technology
Chenxuan Wu, Jun Liu, Junwen Ma, Qiaojuan Yan, Zhengqiang Jiang
Summary: NAT has been shown to extend the lifespan of C. elegans and improve resistance to heat and oxidation stress. The mechanism involves insulin/insulin-like signaling and activation of AMPK, leading to enhanced activity of DAF-16 and induction of autophagy. These findings suggest that NAT could be used as a dietary restriction mimic centered on AMPK and has potential anti-aging effects in higher organisms.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Biology
Yizhou Jiang, Uma Gaur, Zhibai Cao, Sheng-Tao Hou, Wenhua Zheng
Summary: This study reveals the role of dopamine receptors in regulating lifespan in C. elegans, where activation of D2R extends lifespan and healthspan while inhibition of D2R shortens lifespan. D2R signaling regulates lifespan through a dietary restriction mechanism.
Article
Endocrinology & Metabolism
Joshua Jackson, Lena Wischhof, Enzo Scifo, Anna Pellizzer, Yiru Wang, Antonia Piazzesi, Debora Gentile, Sana Siddig, Miriam Stork, Chris E. Hopkins, Kristian Handler, Joachim Weis, Andreas Roos, Joachim L. Schultze, Pierluigi Nicotera, Dan Ehninger, Daniele Bano
Summary: Mitochondrial retrograde signaling can stimulate organelle biogenesis as a compensatory adaptation to abnormal activity of the oxidative phosphorylation (OXPHOS) system. In this study, the researchers investigated the molecular mechanisms promoting mitochondrial maintenance in energy-deprived cells and identified the sphingosine phosphate lyase SPL-1/SGPL1 and the ATFS-1-target HOPS complex subunit VPS-39/VPS39 as critical lifespan modulators. They also found that VPS39 recruitment to the mitochondria may be a common signature associated with altered OXPHOS system in mouse-derived muscles.
MOLECULAR METABOLISM
(2022)
Article
Multidisciplinary Sciences
Elite Possik, Laura-Lee Klein, Perla Sanjab, Ruyuan Zhu, Laurence Cote, Ying Bai, Dongwei Zhang, Howard Sun, Anfal Al-Mass, Abel Oppong, Rasheed Ahmad, Alex Parker, S. R. Murthy Madiraju, Fahd Al-Mulla, Marc Prentki
Summary: Excess nutrients can accelerate aging, but the newly discovered enzyme G3PP can counter metabolic stress and promote healthy aging in C. elegans. Overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics the effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. This overexpression depletes glycogen stores and activates AMPK, HLH-30, and autophagy, promoting healthy aging.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Siqi Jiang, Na Deng, Bisheng Zheng, Tong Li, Rui Hai Liu
Summary: Rhodiola extract was found to significantly extend the lifespan of C. elegans and enhance its stress resistance by regulating gene expression and promoting protein translocation.
Article
Multidisciplinary Sciences
Nan Wu, Yi-Cheng Ma, Xin-Qian Gong, Pei-Ji Zhao, Yong-Jian Jia, Qiu Zhao, Jia-Hong Duan, Cheng-Gang Zou
Summary: Metabolism is closely related to aging, and endogenous metabolites may delay aging and improve health. The activation of the transsulfuration pathway is linked to peroxisome function and biogenesis in long-lived Caenorhabditis elegans worms. Supplementation with alpha-ketobutyrate, an intermediate of the transsulfuration pathway, extends lifespan in wild-type worms. Alpha-ketobutyrate enhances NAD(+) production and improves peroxisome function and biogenesis through the SIR-2.1/SIRT1 pathway. It also promotes the expression of genes related to autophagy and lysosomes, ultimately extending lifespan. Alpha-ketobutyrate also delays cellular senescence in fibroblast cells. Understanding how metabolites modulate longevity is crucial for reducing aging-related disease.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Richard R. Sprenger, Martin Hermansson, Ditte Neess, Lena Sokol Becciolini, Signe Bek Sorensen, Rolf Fagerberg, Josef Ecker, Gerhard Liebisch, Ole N. Jensen, Dennis E. Vance, Nils J. Faergeman, Robin W. Klemm, Christer S. Ejsing
Summary: This study investigates the diurnal regulation of whole-body lipid metabolism through time-series multi-omics analyses of liver and plasma, revealing that molecular oscillations are mainly entrained by adaptations to fasting, food intake, and the postprandial state. The research also highlights the key role of the hepatic phosphatidylethanolamine (PE) methylation pathway in diurnal regulation, leading to the production of two pools of oscillating phosphatidylcholine (PC) molecules in the circulation.
Article
Endocrinology & Metabolism
Ditte Neess, Vibeke Kruse, Ann-Britt Marcher, Mie Rye Waede, Julie Vistisen, Pauline M. Moller, Rikke Petersen, Jonathan R. Brewer, Tao Ma, Georgia Colleluori, Ilenia Severi, Saverio Cinti, Zach Gerhart-Hines, Susanne Mandrup, Nils J. Faergeman
Summary: The loss of ACBP in keratinocytes leads to increased energy expenditure, food intake, browning of adipose tissue, and resistance to diet-induced obesity. These findings highlight the crucial role of the epidermal barrier in maintaining systemic metabolic homeostasis.
MOLECULAR METABOLISM
(2021)
Article
Cell Biology
Kathrine B. Dall, Jesper F. Havelund, Eva B. Harvald, Michael Witting, Nils J. Faergeman
Summary: The study demonstrates that starvation alters the abundance of hundreds of metabolites and lipid species in a temporal- and HLH-30-dependent manner, and that animals lacking the transcription factor HLH-30 rewires their metabolism to largely depend on functional peroxisomes during starvation. Furthermore, supplementation of exogenous fatty acids can prevent premature death of HLH-30 animals under starvation.
Article
Cell Biology
Anne Loft, Soren Fisker Schmidt, Giorgio Caratti, Ulrich Stifel, Jesper Havelund, Revathi Sekar, Yun Kwon, Alba Sulaj, Kan Kau Chow, Ana Jimena Alfaro, Thomas Schwarzmayr, Nikolaj Rittig, Mads Svart, Foivos-Filippos Tsokanos, Adriano Maida, Andreas Blutke, Annette Feuchtinger, Niels Moller, Matthias Blueher, Peter Nawroth, Julia Szendroedi, Nils J. Faergeman, Anja Zeigerer, Jan Tuckermann, Stephan Herzig
Summary: This study investigates the contribution of immune cells to metabolic homeostasis during fasting in healthy subjects. It identifies the glucocorticoid receptor (GR) as a key driver of fasting-induced reprogramming of the macrophage secretome, and shows that lack of macrophage GR impairs induction of ketogenesis during fasting and endotoxemia. This research also highlights the direct influence of liver macrophages on ketogenesis in hepatocytes, providing insights into the immune system's role in regulating metabolic activity during inflammatory diseases and infection.
Article
Gastroenterology & Hepatology
Mette K. Andersen, Line Skotte, Emil Jorsboe, Ryan Polito, Frederik F. Staeger, Peter Aldiss, Kristian Hanghoj, Ryan K. Waples, Cindy G. Santander, Niels Grarup, Inger K. Dahl-Petersen, Lars J. Diaz, Maria Overvad, Ninna K. Senftleber, Bolette Soborg, Christina V. L. Larsen, Clara Lemoine, Oluf Pedersen, Bjarke Feenstra, Peter Bjerregaard, Mads Melbye, Marit E. Jorgensen, Nils J. Faergeman, Anders Koch, Thomas Moritz, Matthew P. Gillum, Ida Moltke, Torben Hansen, Anders Albrechtsen
Summary: Adults with sucrase-isomaltase deficiency have better metabolic health, with lower BMI, body weight, fat percentage, fasting triglyceride, and remnant cholesterol levels. This is likely mediated by higher levels of acetate and reduced sucrose uptake, but not lower caloric intake.
Meeting Abstract
Endocrinology & Metabolism
Julia Bandres-Meriz, Christina Kunz, Jesper Havelund, Nils J. Faergeman, Irene Hurtado De Mendoza, Alejandro Majali-Martinez, Regina Ensenauer, Gernot Desoye
Article
Cell Biology
Dalia Ali, Florence Figeac, Atenisa Caci, Nicholas Ditzel, Clarissa Schmal, Greet Kerckhofs, Jesper Havelund, Nils Faergeman, Alexander Rauch, Michaela Tencerova, Moustapha Kassem
Summary: This study investigated the combined effects of obesity and estrogen deficiency on the skeleton. By feeding ovariectomized mice with a high-fat diet, it was found that obesity and estrogen deficiency can impair bone formation and decrease bone mass, leading to increased bone fragility.
Article
Endocrinology & Metabolism
Sebastian Moller Nguyen Heimburger, Bjorn Hoe, Chris Neumann Nielsen, Natasha Chidekel Bergman, Kirsa Skov-Jeppesen, Bolette Hartmann, Jens Juul Holst, Flemming Dela, Julie Overgaard, Joachim Storling, Tina Vilsboll, Thomas Fremming Dejgaard, Jesper Foged Havelund, Vladimir Gorshkov, Frank Kjeldsen, Nils Joakim Faergeman, Martin Ronn Madsen, Mikkel B. Christensen, Filip Krag Knop
Summary: In men with type 1 diabetes, a 6-day subcutaneous GIP infusion transiently decreased bone resorption and increased NEFA and beta-oxidation. Further, hepatic fat content and supraclavicular skin temperature were increased without affecting WAT transcriptomics, the circulating proteome, lipids, or inflammatory markers.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Julia Bandres-Meriz, Christina Kunz, Jesper F. Havelund, Nils J. Faergeman, Alejandro Majali-Martinez, Regina Ensenauer, Gernot Desoye
Summary: The study found that the metabolome of pregnant women with overweight/obesity is already altered early in pregnancy due to changes in C-peptide. Lipid and amino acid metabolites related to obesity and insulin play a key role in these alterations.
INTERNATIONAL JOURNAL OF OBESITY
(2023)
Article
Multidisciplinary Sciences
Astrid L. Basse, Karen N. Nielsen, Iuliia Karavaeva, Lars R. Ingerslev, Tao Ma, Jesper F. Havelund, Thomas S. Nielsen, Mikkel Frost, Julia Peics, Emilie Dalbram, Morten Dall, Juleen R. Zierath, Romain Barres, Nils J. Faergeman, Jonas T. Treebak, Zachary Gerhart-Hines
Summary: NAMPT controls the molecular clock and metabolic biorhythms in a tissue-specific manner. It plays a key role in the amplitude of the core clock in brown adipose tissue, has moderate dependence on NAD+ biosynthesis in white adipose tissue, and is completely refractory to loss in skeletal muscle. NAMPT also differentially orchestrates oscillation of clock-controlled gene networks and metabolite levels in different tissues.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Vignesh Ramesh, Paradesi Naidu Gollavilli, Luisa Pinna, Mohammad Aarif Siddiqui, Adriana Martinez Turtos, Francesca Napoli, Yasmin Antonelli, Aldo Leal-Egana, Jesper Foged Havelund, Simon Toftholm Jakobsen, Elisa Le Boiteux, Marco Volante, Nils Joakim Faergeman, Ole N. Jensen, Rasmus Siersbaek, Kumar Somyajit, Paolo Ceppi
Summary: This study found an inverse association between short-chain fatty acids and EMT in non-small cell lung cancer patients. In vitro experiments showed that propionate treatment enhanced the epithelial transcriptional program and reduced the EMT phenotype in lung cancer cell lines. Animal experiments also confirmed that propionate can reduce lung cancer metastasis and lymph node spread. Further mechanistic investigation revealed that propionate treatment caused chromatin remodeling through p300-mediated histone acetylation.
EMBO MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Aida Rodriguez Lopez, Maria H. Jorgensen, Jesper F. Havelund, Frederic S. Arendrup, Srinivasa Prasad Kolapalli, Thorbjorn M. Nielsen, Eva Pais, Carsten Jorn Beese, Ahmad Abdul-Al, Anna Constance Vind, Jiri Bartek, Simon Bekker-Jensen, Marta Montes, Panagiotis Galanos, Nils Faergeman, Lotta Happonen, Lisa B. Frankel
Summary: Ribosomes are selectively targeted for degradation by autophagy during cell senescence, contributing to alterations in cell metabolome and the senescence-associated secretory phenotype.
Article
Endocrinology & Metabolism
Catarina Mendes Correia, Stine Marie Praestholm, Jesper Foged Havelund, Felix Boel Pedersen, Majken Storm Siersbaek, Morten Frendo Ebbesen, Zach Gerhart-Hines, Joerg Heeren, Jonathan Brewer, Steen Larsen, Blagoy Blagoev, Nils Joakim Faergeman, Lars Grontved
Summary: Hepatic lipid metabolism is affected by circadian regulation and disruption of the glucocorticoid receptor (GR) leads to hepatic steatosis. In this study, an acute hepatocyte-specific GR knockout model was used to investigate the role of GR in temporal hepatic lipid metabolism. Lipidomics analysis revealed impaired regulation of triglycerides, fatty acids, and sphingolipids in the absence of GR. Dysregulation of lipid metabolism was found to be associated with altered gene expression and increased lipid droplet formation.
Article
Genetics & Heredity
Emil Jorsboe, Mette K. Andersen, Line Skotte, Frederik F. Staeger, Nils J. Faergeman, Kristian Hanghoj, Cindy G. Santander, Ninna K. Senftleber, Lars J. Diaz, Maria Overvad, Ryan K. Waples, Frank Geller, Peter Bjerregaard, Mads Melbye, Christina V. L. Larsen, Bjarke Feenstra, Anders Koch, Marit E. Jorgensen, Niels Grarup, Ida Moltke, Anders Albrechtsen, Torben Hansen
Summary: The common Arctic-specific LDLR p.G137S variant is associated with increased risk of familial hypercholesterolemia (FH) and cardiovascular disease in Greenlanders, affecting up to 30% of the population.
HUMAN GENETICS AND GENOMICS ADVANCES
(2022)
Meeting Abstract
Endocrinology & Metabolism
P. M. Moller, M. H. Petersen, M. E. De Almeida, N. Ortenblad, J. Havelund, N. J. K. Faergeman, K. Hojlund
