Article
Multidisciplinary Sciences
Hannah Guak, Ryan D. Sheldon, Ian Beddows, Alexandra Vander Ark, Matthew J. Weiland, Hui Shen, Russell G. Jones, Julie St-Pierre, Eric H. Ma, Connie M. Krawczyk
Summary: The metabolic programming of dendritic cells (DCs), a type of innate immune cells, can be influenced by different stimuli, which in turn affects their function. While the increased glycolytic metabolism in response to inflammatory stimuli is well-known, the programming of mitochondrial metabolism in DCs is less understood. This study identifies PGC-1 beta as a key regulator of mitochondrial metabolism and inflammation in DCs.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Edmund Battey, Regula Furrer, Jacob Ross, Christoph Handschin, Julien Ochala, Matthew J. Stroud
Summary: PGC-1α plays a critical role in myonuclear accretion during adaptation to endurance training, especially in larger muscle fibers. Myonuclear accretion in PGC-1α mKO mice is slightly affected with increasing fiber size, but is significantly altered in trained larger fibers compared to sedentary mice, highlighting the importance of PGC-1α in myonuclear accretion in these fibers.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Weilei Yao, Baoyin Guo, Taimin Jin, Zhengxi Bao, Tongxin Wang, Shu Wen, Feiruo Huang
Summary: This study investigated the mechanism and effects of garcinol on the regulation of skeletal muscle fiber type transformation. The results showed that garcinol can downregulate the expression of fast myosin heavy chain and upregulate the expression of slow myosin heavy chain. In addition, garcinol promotes the conversion of skeletal muscle fibers from fast-glycolytic type to slow-oxidative type through the p300/PGC-1 alpha signaling pathway in C2C12 myotubes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Laura Pelosi, Maria Grazia Berardinelli, Laura Forcina, Francesca Ascenzi, Emanuele Rizzuto, Marco Sandri, Fabrizio De Benedetti, Bianca Maria Scicchitano, Antonio Musaro
Summary: IL-6 is a pleiotropic cytokine with different and opposite effects under healthy and pathologic conditions. It can stimulate muscle growth in healthy conditions but may lead to muscle wasting in pathological conditions. Increased plasma levels of IL-6 may be associated with stunted growth and muscle wasting.
Article
Biochemistry & Molecular Biology
Mirko Magnone, Sonia Spinelli, Giulia Begani, Lucrezia Guida, Laura Sturla, Laura Emionite, Elena Zocchi
Summary: This study demonstrates that the plant hormone ABA can improve glycemic control and enhance muscle insulin sensitivity and glucose uptake in a murine model of T1D.
Article
Cell Biology
Marta Montori-Grau, David Aguilar-Recarte, Mohammad Zarei, Javier Pizarro-Delgado, Xavier Palomer, Manuel Vazquez-Carrera
Summary: This study found that endoplasmic reticulum (ER) stress downregulates the expression of PGC-1 alpha in skeletal muscle through the activation of ATF4 and the mTOR-CRTC2 pathway. These findings suggest that inhibition of ATF4 and the mTOR-CRTC2 axis could be a therapeutic target for insulin resistant states.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Immunology
Rachel E. Nicholas, Kjell Sandstrom, Jennifer L. Anderson, Willow R. Smith, Molly Wetzel, Priyankana Banerjee, Sanath Kumar Janaka, David T. Evans
Summary: Understanding the interaction between rhesus macaque killer-cell Ig-like receptors (KIRs) and MHC class I ligands such as Mamu-AG is crucial for studying the role of natural killer (NK) cells in this species. The study reveals variation in KIR3DL05 and KIR3DS02 responses to different alleles of Mamu-AG, highlighting the impact of Mamu-AG polymorphisms on KIR recognition.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Bruno Ferreira Mendes, Liliane Vanessa Costa-Pereira, Jullia Alves de Andrade, Caique Olegario Diniz Magalhaes, Ramona Ramalho Souza de Pereira, Elizabethe Adriana Esteves, Ricardo Cardoso Cassilhas, Eric Francelino Andrade, Fernando Gripp, Flavio Castro de Magalhaes, Kinulpe Honorato Sampaio, Fabiano Trigueiro Amorim, Marco Fabricio Dias-Peixoto
Summary: This study compares the cardiometabolic and cellular adaptative responses in rats after 8 weeks of high-intensity interval training (HIIT) performed in either a single or three shorter daily sessions. The results indicate that both training methods have similar effects on resting VO2 and VO(2)max, cardiac function, and mitochondria density, while the three shorter daily sessions of HIIT are more effective in reducing visceral fat weight, adipocyte size, and improving insulin tolerance.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Rajesh Parsanathan, Sushil K. Jain
Summary: Irisin, a novel myokine, is involved in glucose homeostasis through the activation of PGC-1 alpha/FNDC5/Irisin signaling pathway. This study found that deficiency of hydrogen sulfide (H2S) leads to decreased secretion of FNDC5 and Irisin and alters glucose metabolism, while upregulation of H2S levels has beneficial effects on glucose homeostasis.
Article
Cell Biology
Penghua Fang, Long Han, Mei Yu, Shiyu Han, Mengyuan Wang, Yujie Huang, Wancheng Guo, Qingbo Wei, Wenbing Shang, Wen Min
Summary: Chemerin deficiency affects glucose metabolism in mice, leading to elevated blood glucose levels and glucose intolerance. Moreover, chemerin deficiency also impacts the expression levels of GLUT4 and PGC-1 alpha in both skeletal muscle and adipose tissue.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Boyu Yang, Qiongli Yu, Bo Chang, Qi Guo, Sitong Xu, Xuejie Yi, Shicheng Cao
Summary: The study demonstrates the potential of AMPK/PGC-1 alpha pathway in mediating the secretion and/or production of MOTS-c in skeletal muscle, suggesting the roles of exercise intervention and recombinant MOTS-c in treating obesity and diabetes mellitus.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Cell Biology
Lucy Penfold, Angela Woods, Alice E. Pollard, Julia Arizanova, Eneko Pascual-Navarro, Phillip J. Muckett, Marian H. Dore, Alex Montoya, Chad Whilding, Louise Fets, Joao Mokochinski, Theodora A. Constantin, Anabel Varela-Carver, Damien A. Leach, Charlotte L. Bevan, Alexander Yu. Niktin, Zoe Hall, David Carling
Summary: Emerging evidence suggests that metabolic dysregulation is a driver of prostate cancer (PCa) progression and metastasis. AMP-activated protein kinase (AMPK), a master regulator of metabolism, has a protective effect on PCa progression in vivo. AMPK activation induces the expression of PGC1a, leading to catabolic metabolic reprogramming in PCa cells. This reprogramming inhibits PCa disease progression and is associated with the inhibition of a gene network involved in cell cycle regulation.
Article
Physiology
Arkady Uryash, Alfredo Mijares, Carlos E. Lopez, Jose A. Adams, Jose R. Lopez
Summary: Chronic elevated muscle Ca2+ levels may decrease insulin-stimulated glucose uptake, leading to hyperglycemia. By reducing muscle Ca2+ levels, muscle glucose uptake can be improved, alleviating hyperglycemia. This phenomenon may be related to the expression and subcellular fractionation of GLUT4.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Qi Liu, Su Pan, Pengyang Li, Richard A. F. Dixon
Summary: Metabolic plasticity is crucial for cell survival in a harsh environment. In this study, we investigated the effect of Hippo pathway inhibition on cell adaptations under challenging conditions. We found that Hippo pathway inhibition enhanced ATP production, mitochondrial parameters, glycolysis, and glycolytic reserves in cells. The inhibition also upregulated metabolic pathways to support increased energy production and counteract oxidative stress. Additionally, cells showed the ability to increase fatty acid oxidation or glucose-coupled oxidative phosphorylation to compensate for substrate limitations.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Mingjuan Gu, Zhuying Wei, Xueqiao Wang, Yang Gao, Dong Wang, Xuefei Liu, Chunling Bai, Guanghua Su, Lei Yang, Guangpeng Li
Summary: This study generated myostatin-knockout (Mstn-KO) mice using CRISPR/Cas9 technology, and found that Mstn knockout led to significantly larger skeletal muscles and regulated organ weights of mice. Moreover, Mstn knockout reduced basal metabolic rate, mitochondrial function, and thermogenesis. Mechanistically, Mstn knockout inhibited the AMPK/SIRT1/PGC1α signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Nicholas Barnaba, Jeannine R. LaRocque
Summary: Dysregulation of the G1-S transition in melanoma leads to reliance on the G2-M checkpoint for cell cycle control. The concept of cell cycle-mediated synthetic lethality for melanoma treatment involves targeting G1-S mutations with G2-M inhibitors to specifically kill melanoma cells. This approach exploits the vulnerability of melanoma cells lacking G1-S checkpoints to mitotic catastrophe induced by G2-M inhibition and DNA damage.
Article
Biology
Michael A. Petr, Irene Alfaras, Melissa Krawcyzk, Woei-Nan Bair, Sarah J. Mitchell, Christopher H. Morrell, Stephanie A. Studenski, Nathan L. Price, Kenneth W. Fishbein, Richard G. Spencer, Morten Scheibye-Knudsen, Edward G. Lakatta, Luigi Ferrucci, Miguel A. Aon, Michel Bernier, Rafael de Cabo
Summary: The study found that aging and frailty are associated with declines in gait speed, increased energetic cost of physical activity, and decreased working capacity. Aging and functional decline prompt organs to rewire their metabolism towards redox-related pathways.
Editorial Material
Geriatrics & Gerontology
William K. Smith, Donald K. Ingram, Rafael de Cabo, Paul Pasquina
Article
Nutrition & Dietetics
David S. Ludwig, Louis J. Aronne, Arne Astrup, Rafael de Cabo, Lewis C. Cantley, Mark Friedman, Steven B. Heymsfield, James D. Johnson, Janet C. King, Ronald M. Krauss, Daniel E. Lieberman, Gary Taubes, Jeff S. Volek, Eric C. Westman, Walter C. Willett, William S. Yancy, Cara B. Ebbeling
Summary: The obesity pandemic may be not only caused by excessive consumption of high-energy foods and lack of exercise, but also related to biological mechanisms. The carbohydrate-insulin model proposes a new cognitive framework, emphasizing hormonal responses to a high glycemic load diet.
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2021)
Article
Cell Biology
Irene Alfaras, Keisuke Ejima, Camila Vieira Ligo Teixeira, Clara Di Germanio, Sarah J. Mitchell, Samuel Hamilton, Luigi Ferrucci, Nathan L. Price, David B. Allison, Michel Bernier, Rafael de Cabo
Summary: In this study, the degree of phenotypic variation in a cohort of 24-month-old male C57BL/6 mice was assessed, using a resampling approach to calculate error rates and power for statistical tests. The research found that the number of animals required for adequate power differs depending on the type of statistical test being conducted, providing an analysis for informed decision-making on sample size without prior assumptions of a theoretical distribution.
Article
Biology
Tina Schumann, Joerg Koenig, Christian von Loeffelholz, Daniel F. Vatner, Dongyan Zhang, Rachel J. Perry, Michel Bernier, Jason Chami, Christine Henke, Anica Kurzbach, Nermeen N. El-Agroudy, Diana M. Willmes, Dominik Pesta, Rafael de Cabo, John F. O. Sullivan, Eric Simon, Gerald Shulman, Bradford S. Hamilton, Andreas L. Birkenfeld
Summary: Schumann et al. demonstrate that the loss of a lactate transporter Slc16a13 increases mitochondrial respiration in the liver, which reduces hepatic lipid accumulation while increasing hepatic insulin sensitivity in mice fed a high-fat diet. This study suggests SLC16A13 as a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease.
COMMUNICATIONS BIOLOGY
(2021)
Letter
Nutrition & Dietetics
David S. Ludwig, Louis J. Aronne, Arne Astrup, Rafael de Cabo, Lewis C. Cantley, Mark Friedman, Steven B. Heymsfield, James D. Johnson, Janet C. King, Ronald M. Krauss, Daniel E. Lieberman, Gary Taubes, Jeff S. Volek, Eric C. Westman, Walter C. Willett, William S. Yancy, Cara B. Ebbeling
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Geriatrics & Gerontology
Giovanni E. Finesso, Ross A. McDevitt, Roshni Roy, Lauren R. Brinster, Andrea Di Francesco, Theresa Meade, Rafael de Cabo, Luigi Ferrucci, Kathy A. Perdue
Summary: Age-dependent differences in DNA methylation can predict age, but the presence of neoplastic cells may affect the accuracy of the epigenetic clock.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Geriatrics & Gerontology
Sara Lopez-Bellon, Sandra Rodriguez-Lopez, Jose A. Gonzalez-Reyes, M. Isabel Buron, Rafael de Cabo, Jose M. Villalba
Summary: The study showed that overexpression of CYB5R3 can activate mitochondrial function in skeletal muscle, delaying aging process and improving mitochondrial structure and autophagic recycling in old mice.
Review
Oncology
Lea Montegut, Rafael de Cabo, Laurence Zitvogel, Guido Kroemer
Summary: In population studies, dietary patterns have an impact on cancer development, progression, and therapeutic response. However, interventional dietary trials have had limited effect on cancer prevention and treatment. Standardization of nutritional interventions combined with high-level mode-of-action studies has the potential to identify specific entities and pathways with anti-cancer properties.
Article
Geriatrics & Gerontology
Sara E. Espinoza, Sundeep Khosla, Joseph A. Baur, Rafael de Cabo, Nicolas Musi
Summary: The geroscience hypothesis suggests that targeting key hallmarks of aging can improve healthspan and prevent age-related diseases. Several pharmacological interventions, including senolytics, NAD(+) boosters, and metformin, are being studied for their potential benefits. Preclinical studies show that senolytic drugs improve healthspan in rodents, while increasing NAD(+) through supplementation appears to extend healthspan in model organisms. Metformin, on the other hand, has pleiotropic effects and is being examined for its potential to improve healthspan and prevent frailty in clinical trials. However, further research is needed to determine their efficacy, safety, target populations, and long-term outcomes.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Cell Biology
Jayanta Kumar Das, Nirad Banskota, Julian Candia, Michael E. Griswold, Melissa Orenduff, Rafael de Cabo, David L. Corcoran, Sai Krupa Das, Supriyo De, Kim Marie Huffman, Virginia B. Kraus, William E. Kraus, Corby K. Martin, Susan B. Racette, Leanne M. Redman, Birgit Schilling, Daniel W. Belsky, Luigi Ferrucci
Summary: Using high-depth RNA-Seq analysis, this study found that caloric restriction (CR) positively affects skeletal muscle quality in humans and alters the gene expression and splicing profiles of biological pathways affected by CR in model organisms.
Article
Cell Biology
Hitoshi Watanabe, Wen Du, Jinsook Son, Lina Sui, Shun-ichiro Asahara, Irwin J. Kurland, Taiyi Kuo, Takumi Kitamoto, Yasutaka Miyachi, Rafael de Cabo, Domenico Accili
Summary: Sulfonylureas are effective and affordable antidiabetic drugs, but chronic use leads to secondary failure. Cytochrome b5 reductase 3 (Cyb5r3) down-regulation is identified as a mechanism of secondary SU failure and can be successfully reversed. Cyb5r3 activators can rescue secondary SU failure and potentially rehabilitate SU use in diabetes.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase can utilize both Delta psi(m)-driven H+- and K+-transport to synthesize ATP under physiological conditions. The presence of K+ increases ATP synthesis rate in isolated mitochondria while also increasing oxygen consumption rate. The data obtained from purified F1Fo single molecule experiments are consistent with the functional data observed in intact mitochondria.
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase serves as the primary way for K+ to enter mitochondria, and its activity can be upregulated by endogenous survival-related proteins via IF1. The interaction between IF1 and Bcl-xL or Mcl-1 enhances ATP synthase's efficiency and limits ischemia-reperfusion injury.