Article
Cell Biology
Marisa Ferreira-Marques, Andre Carvalho, Claudia Cavadas, Celia A. Aveleira
Summary: Caloric restriction has been shown to improve age-related diseases and extend lifespan by activating autophagy through PI3K/AKT/MTOR inhibition and ERK1/2-MAPK activation. Understanding the role of these kinases in autophagy regulation may lead to more targeted therapeutic strategies for age-related disorders.
Article
Cell Biology
Alexander M. Wolf
Summary: Understanding the molecular mechanisms of normal aging is crucial for improving human health span. Caloric restriction delays aging, but its benefits depend on the weight status of control mice. Pharmacological interventions that increase lifespan and reduce body weight may not be suitable for healthy weight individuals.
MECHANISMS OF AGEING AND DEVELOPMENT
(2021)
Review
Biochemistry & Molecular Biology
Pieter de Lange, Assunta Lombardi, Elena Silvestri, Federica Cioffi, Antonia Giacco, Stefania Iervolino, Giuseppe Petito, Rosalba Senese, Antonia Lanni, Maria Moreno
Summary: The adipose organ plays a crucial role in metabolic functions and its aging process leads to metabolic disorders, impacting healthy aging. Cellular senescence in adipose tissue affects adipogenesis, inflammation, and adipocytokine production, leading to systemic inflammation, insulin resistance, and declined physiological features. Aging fat depots involve various cell types, highlighting their contribution to metabolic disorders. Targeting mitochondria may hold potential in managing adipose tissue senescence and treating age-related metabolic disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Erwan Eriau, Juliette Paillet, Guido Kroemer, Jonathan G. Pol
Summary: Reduced food intake and caloric restriction mimetics have been shown to increase healthy lifespan, reduce cancer incidence, and enhance responses to certain cancer treatments. These effects are mediated by cellular mechanisms and vary between cancer cells and healthy cells due to differences in metabolic requirements. Additionally, both reduced food intake and caloric restriction mimetics can induce autophagy, improving the efficacy of certain cancer treatments that induce immunogenic cell death and enhance the therapeutic efficacy of chemo-immunotherapies.
Article
Nutrition & Dietetics
Chanisa Thonusin, Patcharapong Pantiya, Aphisek Kongkaew, Wichwara Nawara, Busarin Arunsak, Sirawit Sriwichaiin, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: Exercise and caloric restriction have different effects on skeletal muscle metabolism during aging. Exercise is more effective in improving fatty acid oxidation and oxidative phosphorylation, while caloric restriction reduces oxidative stress in skeletal muscle.
Review
Medicine, General & Internal
Lei Pang, Xi Jiang, Xin Lian, Jie Chen, Er-Fei Song, Lei-Gang Jin, Zheng-Yuan Xia, Hai-Chun Ma, Yin Cai
Summary: Graphene, a two-dimensional material composed of a single layer of carbon atoms, is gaining significant attention in the field of electronics due to its excellent conductivity and high chemical stability.
MILITARY MEDICAL RESEARCH
(2022)
Article
Geriatrics & Gerontology
Sandeep Singh, Raushan Kumar, Geetika Garg, Abhishek Kumar Singh, Avnish Kumar Verma, Akalabya Bissoyi, Syed Ibrahim Rizvi
Summary: The study demonstrates that spermidine can provide neuroprotection by regulating autophagy, antioxidant levels, and reducing neuroinflammation, combating aging-induced oxidative stress. This suggests that spermidine may be beneficial for neuroprotection during aging and age-related disorders.
Review
Nutrition & Dietetics
Sebastian J. Hofer, Sergio Davinelli, Martina Bergmann, Giovanni Scapagnini, Frank Madeo
Summary: Human diet and dietary patterns play a crucial role in health status, with high-calorie Western-style diets linked to non-communicable diseases and calorie-reduced health-promoting diets showing promising results. Pharmacological Caloric Restriction Mimetics (CRMs) have attracted interest as potential candidates to mimic effects induced by caloric restriction.
FRONTIERS IN NUTRITION
(2021)
Article
Geriatrics & Gerontology
Megan E. Ramaker, David L. Corcoran, Abner T. Apsley, Michael S. Kobor, Virginia B. Kraus, William E. Kraus, David T. S. Lin, Melissa C. Orenduff, Carl F. Pieper, Reem Waziry, Kim M. Huffman, Daniel W. Belsky
Summary: Calorie restriction has been shown to increase healthy lifespan and slow down aging-associated DNA methylation changes. A study conducted in humans found that calorie restriction can alter age-related DNA methylation patterns but no significant changes were observed at individual CpG sites.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
Gladys Ferrere, Maryam Tidjani Alou, Peng Liu, Anne-Gaelle Goubet, Marine Fidelle, Oliver Kepp, Sylvere Durand, Valerio Iebba, Aurelie Fluckiger, Romain Daillere, Cassandra Thelemaque, Claudia Grajeda-Iglesias, Carolina Alves Costa Silva, Fanny Aprahamian, Deborah Lefevre, Liwei Zhao, Bernhard Ryffel, Emeline Colomba, Monica Arnedos, Damien Drubay, Conrad Rauber, Didier Raoult, Francesco Asnicar, Tim Spector, Nicola Segata, Lisa Derosa, Guido Kroemer, Laurence Zitvogel
Summary: Limited experimental evidence suggests a link between nutrition and cancer immunosurveillance. This study demonstrates that ketogenic diet induces an anti-tumor effect through 3HB-mediated T cell-mediated cancer immunosurveillance. 3HB prevents immune checkpoint inhibition and promotes the expansion of specific T cells, while KD also leads to compositional changes in gut microbiota.
Review
Cardiac & Cardiovascular Systems
Sebastiano Sciarretta, Maurizio Forte, Francesca Castoldi, Giacomo Frati, Francesco Versaci, Junichi Sadoshima, Guido Kroemer, Maria Chiara Maiuri
Summary: Caloric restriction mimetics have shown potential as therapeutic agents for cardiovascular diseases by mimicking the effects of caloric restriction through activating autophagy and ameliorating cardiac function. These compounds can reduce cardiac hypertrophy and maladaptive remodelling in animal models of various cardiac diseases, and may have future clinical applications.
CARDIOVASCULAR RESEARCH
(2021)
Review
Cell Biology
Jingfang Zhai, William H. H. Kongsberg, Yinbo Pan, Canhua Hao, Xiaojing Wang, Jie Sun
Summary: Research suggests that dietary changes can alter epigenetic marks associated with aging. Caloric restriction (CR) is considered an intervention to regulate aging and prolong lifespan, and has made some progress by regulating aging-related signaling pathways and intercellular signaling molecules. This review focuses on autophagy and epigenetic modifications to elaborate the molecular mechanisms by which CR delays aging by triggering autophagy, epigenetic modifications, and their interaction.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Nutrition & Dietetics
Chaise Murphy, Laura D. Bilek, Karsten Koehler
Summary: The study suggests that low energy availability (LEA) may negatively impact bone health, with high-protein diets not attenuating these effects. LEA appears to shift bone turnover in favor of bone resorption.
Review
Nutrition & Dietetics
Julia Voglhuber, Senka Ljubojevic-Holzer, Mahmoud Abdellatif, Simon Sedej
Summary: Global life expectancy is increasing, as is the burden of cardiovascular disease. Dietary restriction can improve cardiovascular risk factors, but challenges in adherence have led to the investigation of alternative eating patterns and pharmacological alternatives.
FRONTIERS IN NUTRITION
(2021)
Review
Geriatrics & Gerontology
Apoorv Sharma, Abhishek Kumar Singh
Summary: Aging-induced neurodegenerative diseases (NDs) are a growing health problem worldwide, and oxidative stress is considered a potential cause. Currently, there are no drugs available for the treatment of NDs, so it is necessary to develop strategies/treatments to prevent or cure these age-related diseases. Caloric restriction and intermittent fasting have shown positive effects on healthspan and lifespan, but strict adherence to these routines is difficult, leading to the development of calorie restriction mimetics (CRMs). CRMs are natural compounds that mimic the effects of caloric restriction and activate autophagy. They have been found to regulate redox signaling, enhance antioxidant defense systems, and inhibit ROS generation. Additionally, CRMs also promote neuronal cell survival by regulating redox-sensitive signaling pathways. This article discusses the neuroprotective effects of various CRMs at the molecular and cellular levels during brain aging, and highlights their potential as a cornerstone in the pharmaceutical arsenal against aging and age-related pathologies.
Article
Biology
Zhanat Koshenov, Furkan E. Oflaz, Martin Hirtl, Benjamin Gottschalk, Rene Rost, Roland Malli, Wolfgang F. Graier
Summary: The study investigates the regulation of basal mitochondrial bioenergetics and reveals that Ca2+ fluxes from ER-mitochondria contact sites control basal mitochondrial metabolism and energetics. The researchers identify citrin as a primary regulator of this process and show that manipulation of Ca2+ dynamics can reprogram cellular and mitochondrial metabolism.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Furkan E. Oflaz, Zhanat Koshenov, Martin Hirtl, Rene Rost, Roland Malli, Wolfgang F. Graier
Summary: The study revealed that S1R plays an important role in cancer energy metabolism. Activation of S1R increases mitochondrial bioenergetics while reducing reliance on aerobic glycolysis in cancer cells. S1R antagonist, on the other hand, increases aerobic glycolysis in S1R expressing cancer cell line.
Article
Biochemistry & Molecular Biology
Christiane Klec, Erik Knutsen, Daniela Schwarzenbacher, Katharina Jonas, Barbara Pasculli, Ellen Heitzer, Beate Rinner, Katarina Krajina, Felix Prinz, Benjamin Gottschalk, Peter Ulz, Alexander Deutsch, Andreas Prokesch, Stephan W. Jahn, S. Mohammad Lellahi, Maria Perander, Raffaela Barbano, Wolfgang F. Graier, Paola Parrella, George Adrian Calin, Martin Pichler
Summary: The RNA-binding protein ALYREF plays a significant role in breast carcinogenesis by regulating the two isoforms of NEAT1, which in turn affects cellular growth, apoptosis, and mitochondrial energy metabolism. This study provides novel insights into the molecular mechanisms underlying breast cancer and has important implications for its treatment and prevention.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Emrah Eroglu, Wolfgang F. Graier, Roland Malli
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Transplantation
Andras T. Deak, Katarina Belic, Anna-Maria Meissl, Katharina Artinger, Kathrin Eller, Bernd Rechberger, Tobias Niedrist, Wolfgang F. Graier, Roland Malli, Helmut Bischof, Sandra Burgstaller, Sandra Blass, Alexander Avian, Alexander R. Rosenkranz, Alexander H. Kirsch
Summary: This study assessed the performance of genetically encoded potassium-ion indicators (GEPIIs) in measuring salivary potassium concentration and found that salivary potassium levels exhibited similar kinetics to plasma potassium levels. However, further research is needed to determine if saliva could be a suitable sample type for monitoring plasma potassium levels.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Biology
Benjamin Gottschalk, Zhanat Koshenov, Markus Waldeck-Weiermair, Snjezana Radulovic, Furkan E. Oflaz, Martin Hirtl, Olaf A. Bachkoenig, Gerd Leitinger, Roland Malli, Wolfgang F. Graier
Summary: This study reveals the role of MICU1 in controlling the spatial membrane potential gradients in mitochondria, with changes in SMPGs and spatial cristae depolarization occurring when Ca2+ binds to MICU1.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Dominic Gross, Helmut Bischof, Selina Maier, Katharina Sporbeck, Andreas L. Birkenfeld, Roland Malli, Peter Ruth, Tassula Proikas-Cezanne, Robert Lukowski
Summary: Ca2+-activated K+ channels of intermediate conductance (IK) play a crucial role in the remodeling of metabolic pathways in breast cancer cells, and their depletion leads to reduced metabolic activity and energy shortage. The loss of IK alters cellular K+ and Ca2+ homeostasis, mitochondrial membrane potential, and ultimately reduces ATP-production, causing breast cancer cells to upregulate AMP-activated protein kinase activity to compensate for energy deficiency through autophagy.
CELL DEATH & DISEASE
(2022)
Retraction
Cell Biology
Andreas Yiallouris, Ioannis Patrikios, Elizabeth O. Johnson, Evangelia Sereti, Konstantinos Dimas, Cristian De Ford, Natalia U. Fedosova, Wolfgang F. Graier, Kleitos Sokratous, Kyriakos Kyriakou, Anastasis Stephanou
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Benjamin Gottschalk, Zhanat Koshenov, Olaf A. Bachkoenig, Rene Rost, Roland Malli, Wolfgang F. Graier
Summary: Endoplasmic reticulum (ER) critically depends on ATP supply for its functions. The disruption of protein trafficking and folding in the ER leads to ER stress and the unfolded protein response (UPR). During ER stress, the stability and lifetime of mitochondrial associated ER membranes (MAM) increase, resulting in an increase in mitochondrial activity and ATP generation, which in turn enhances the ATP supply for the ER. The increased stability and lifetime of MAMs during ER stress rely on the mitochondrial fusion protein Mitofusin2 (MFN2). Knockdown of MFN2 impairs the response of mitochondria to ER stress and reduces ATP supply for the ER.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Furkan E. Oflaz, Zhanat Koshenov, Martin Hirtl, Olaf A. Bachkoenig, Wolfgang F. Graier, Benjamin Gottschalk
Summary: Mitochondrial uncoupling proteins UCP1 and UCP2 have different molecular mechanisms for executing their mitochondria uncoupling function, with UCP1 dissipating the proton motive force and UCP2 modulating the permeability of the cristae junction. This mini-review discusses the molecular mechanisms of UCP1 in brown adipose tissue and UCP2 in aged and cancer non-excitable cells, and the synergistic effects of both UCPs with the mitochondrial Ca2+ uptake machinery.
Article
Genetics & Heredity
Lukas Kaufmann, Johannes Pilic, Lisa Auinger, Anna-Lena Mayer, Jasmin Blatterer, Johann Semmler-Bruckner, Safdar Abbas, Khurram Rehman, Muhammad Ayaz, Wolfgang F. Graier, Roland Malli, Erwin Petek, Klaus Wagner, Ali Al Kaissi, Muzammil Ahmad Khan, Christian Windpassinger
Summary: Restrictive dermopathy (RD) is a lethal condition caused by loss-of-function mutations in ZMPSTE24, while mutations preserving residual enzymatic activity lead to mandibuloacral dysplasia with type B lipodystrophy (MADB) phenotype. A new homozygous loss-of-function mutation in ZMPSTE24 was identified in two consanguineous Pakistani families with MADB. Functional analysis revealed that alternative translation initiation sites were utilized, preventing complete loss of protein function and explaining the relatively mild phenotype in affected patients. Our findings suggest considering the creation of new potential start codons in other disease-associated genes with N-terminal mutations.
Article
Biochemistry & Molecular Biology
Madeleine Goeritzer, Katharina B. Kuentzel, Sarah Beck, Melanie Korbelius, Silvia Rainer, Ivan Bradic, Dagmar Kolb, Marion Mussbacher, Waltraud C. Schrottmaier, Alice Assinger, Axel Schlagenhauf, Rene Rost, Benjamin Gottschalk, Thomas O. Eichmann, Thomas Zuellig, Wolfgang F. Graier, Nemanja Vujic, Dagmar Kratky
Summary: Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) and plays a role in platelet function. MGL deficiency leads to decreased platelet aggregation and impaired response to collagen activation, resulting in reduced thrombus formation and prolonged bleeding time. Genetic deletion of MGL is associated with altered thrombogenesis in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cell Biology
Benjamin Gottschalk, Roland Malli, Wolfgang F. Graier
Summary: Changes in mitochondrial ultrastructure and dynamics, including cytochrome c release, membrane potential rearrangement, and mitochondrial Ca2+ uptake dynamics, are observed in MICU1(-/-) cells due to its sensitivity to Ca2+ and its binding to Mic60 and CHCHD2. MICU1 is not only an interaction partner and regulator of the MCU complex, but also plays a crucial role in determining mitochondrial ultrastructure and initiating apoptosis.
Article
Chemistry, Multidisciplinary
Zuzana Klepcova, Ivana Spakova, Corina T. T. Madreiter-Sokolowski, Wolfgang Graier, Katarina Kalinova, Erika Samolova, Romana Smolkova, Lukas Smolko, Miroslava Rabajdova
Summary: Two novel Mn(II) complexes with fenamic acid and flufenamic acid as ligands and neocuproine as a supporting ligand were synthesized and characterized. The complexes exhibit moderate radical scavenging activity and cytotoxic effects on selected cell lines, with the flufenamic acid complex being able to induce apoptosis. Both complexes target inflammatory processes on a cellular level.
NEW JOURNAL OF CHEMISTRY
(2023)
