Review
Biochemistry & Molecular Biology
Patrick C. Bradshaw
Summary: Acetyl-CoA plays important roles in regulating gene expression and promoting longevity, with decreased cytoplasmic levels potentially contributing to longevity and increased nuclear levels aiding in histone acetylation and lifespan extension. Future research should focus on the role of nuclear acetyl-CoA and histone acetylation in controlling hypothalamic inflammation, a key driver of organismal aging.
Article
Cell Biology
Rashpal S. Dhillon, Yiming (Amy) Qin, Paul R. van Ginkel, Vivian X. Fu, James M. Vann, Alexis J. Lawton, Cara L. Green, Fulvia B. Manchado-Gobatto, Claudio A. Gobatto, Dudley W. Lamming, Tomas A. Prolla, John M. Denu
Summary: SIRT3 plays a crucial role in calorie restriction-mediated lifespan and healthspan regulation, but its relationship with mitochondrial function and aerobic adaptation remains unclear. This study reveals that while SIRT3 is required for overall aerobic capacity, it is not essential for lifespan extension under calorie restriction.
Article
Endocrinology & Metabolism
Zhijun Zhao, Jing Cao, Chaoqun Niu, Menghuan Bao, Jiaqi Xu, Daliang Huo, Shasha Liao, Wei Liu, John R. Speakman
Summary: The study reveals that exposure to a temperature of 32.5 degrees C leads to a reduced lifespan in both mice and hamsters, coinciding with lowered metabolic rate and elevated body temperature. This demonstrates the significant impact of body temperature and metabolic rate on lifespan.
Article
Chemistry, Medicinal
Youchao Deng, Sunbin Deng, Yi-Hsun Ho, Sarah M. Gardner, Zhi Huang, Ronen Marmorstein, Rong Huang
Summary: The study designed and prepared a series of highly potent NatD bisubstrate inhibitors, showing high specificity towards NatD and strong competitive characteristics, providing a rational path for future inhibitor development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biology
Brooke Zanco, Christen K. Mirth, Carla M. Sgro, Matthew D. W. Piper
Summary: Research on fruit flies shows that the influence of protein and carbohydrates on lifespan is indirect, affecting the distribution of dietary sterols. Supplementing with cholesterol can rescue the shortened lifespan caused by high protein: carbohydrate diets. This highlights the complex and indirect effects of nutrient-dependent trade-offs on life histories.
Article
Multidisciplinary Sciences
Charlotte M. Francois, Thomas Pihl, Marion Dunoyer de Segonzac, Chloe Herault, Bruno Hudry
Summary: This study reveals the interaction between cellular metabolism and differentiation, with circulating citrate regulating sperm production through specific protein post-translational modification.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Cell Biology
Lan Jiang, Tianyun Shen, Xinyuan Wang, Lunzhi Dai, Kefeng Lu, Huihui Li
Summary: Posttranslational modification plays a crucial role in regulating protein functions. The functions and mechanisms of N-terminal acetylation, which occurs on the first amino acids of proteins, in the field of macroautophagy/autophagy are not well understood. Recent studies have shown that the N-terminal acetyltransferase NatB is essential for autophagy and it modifies actin cytoskeleton constituent Act1 and dynamin-like GTPase Vps1, promoting the formation and fusion of autophagosomes.
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
Biochemistry & Molecular Biology
Pedro Latorre-Muro, Josue Baeza, Ramon Hurtado-Guerrero, Thomas Hicks, Ignacio Delso, Cristina Hernandez-Ruiz, Adrian Velazquez-Campoy, Alexis J. Lawton, Jesus Angulo, John M. Denu, Jose A. Carrodeguas
Summary: This study demonstrates that PCK1 can undergo self-acetylation without the need for p300, affecting enzymatic activity. It also reveals that the binding of acetyl-CoA to the active site of PCK1 is specific and metal dependent.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Yao Li, Yueling Zhao, Xiaojie Yan, Chen Ye, Sara Weirich, Bing Zhang, Xiaolu Wang, Lili Song, Chenhao Jiang, Albert Jeltsch, Cheng Dong, Wenyi Mi
Summary: The N-degron pathway is important for maintaining protein homeostasis. This study reveals that ZER1 and ZYG11B can recognize small N-terminal residues other than glycine. N-terminal serine, alanine, and cysteine undergo N-terminal acetylation, mediated by N-terminal acetyltransferase (NAT), which prevents their recognition by ZER1/ZYG11B. The crystal structures of ZER1 and ZYG11B bound to various non-acetylated small N-terminal residues provide insights into the mechanism of substrate recognition.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Amrendra Mishra, Hamed Mirzaei, Novella Guidi, Manlio Vinciguerra, Alice Mouton, Marina Linardic, Francesca Rappa, Rosario Barone, Gerardo Navarrete, Min Wei, Sebastian Brandhorst, Stefano Di Biase, Todd E. Morgan, S. Ram Kumar, Peter S. Conti, Matteo Pellegrini, Michel Bernier, Rafael de Cabo, Valter D. Longo
Summary: Research shows that a monthly cycle of 5 days of a fasting-mimicking diet can prevent obesity and related detrimental effects on cardiometabolic health and lifespan in mice. The fasting-mimicking diet inhibits obesity by reducing fat accumulation and improves heart function and resistance to cardiotoxins. It also prevents issues like hyperglycemia, hypercholesterolemia, and hyperleptinemia, while improving glucose and insulin tolerance.
Editorial Material
Multidisciplinary Sciences
Shaunak Deota, Satchidananda Panda
Summary: By combining calorie restriction, fasting, and regulating circadian rhythms, mice can achieve a long and healthy life.
Article
Multidisciplinary Sciences
A. Roichman, S. Elhanati, M. A. Aon, I Abramovich, A. Di Francesco, Y. Shahar, M. Y. Avivi, M. Shurgi, A. Rubinstein, Y. Wiesner, A. Shuchami, Z. Petrover, I Lebenthal-Loinger, O. Yaron, A. Lyashkov, C. Ubaida-Mohien, Y. Kanfi, B. Lerrer, P. J. Fernandez-Marcos, M. Serrano, E. Gottlieb, R. de Cabo, H. Y. Cohen
Summary: The study demonstrates that overexpression of SIRT6 extends lifespan in mice and optimizes energy homeostasis in old age, delaying frailty and preserving healthy aging. Aged SIRT6-transgenic mice maintain hepatic glucose output and glucose homeostasis through improved utilization of two major gluconeogenic precursors, lactate, and glycerol.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Pengjiao Hou, Wei Hao, Bo Qin, Mengyun Li, Rong Zhao, Sheng Cui
Summary: Schlafen11 is a well-studied protein that plays important roles in cancer therapy and virus-host interactions. The crystal structure and biochemical characteristics of the N-terminal domain (NTD) of Schlafen11 were determined, revealing its potent RNase activity towards type I and II tRNAs and rRNAs. These findings enhance our understanding of the Schlafen family.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Kengo Watanabe, Tomasz Wilmanski, Priyanka Baloni, Max Robinson, Gonzalo G. Garcia, Michael R. Hoopmann, Mukul K. Midha, David H. Baxter, Michal Maes, Seamus R. Morrone, Kelly M. Crebs, Charu Kapil, Ulrike Kusebauch, Jack Wiedrick, Jodi Lapidus, Lance Pflieger, Christopher Lausted, Jared C. Roach, Gwenlyn Glusman, Steven R. Cummings, Nicholas J. Schork, Nathan D. Price, Leroy Hood, Richard A. Miller, Robert L. Moritz, Noa Rappaport
Summary: Aging is characterized by progressive deterioration in homeostasis, which requires a systems-level perspective to investigate the molecular dysregulation of underlying biological processes. This study examines the systemic changes in molecular regulation of biological processes under different lifespan-extending interventions. The findings suggest that these interventions generally tighten the regulation of biological modules, particularly in processes such as fatty acid oxidation, immune response, and stress response.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Liping Liu, Zhenxin Yan, Beth A. Osia, Jerzy Twarowski, Luyang Sun, Juraj Kramara, Rosemary S. Lee, Sandeep Kumar, Rajula Elango, Hanzeng Li, Weiwei Dang, Grzegorz Ira, Anna Malkova
Summary: Break-induced replication (BIR) repairs DNA double-strand breaks and plays a role in genome instability, with enzymes required for BIR synthesis identified. New research shows BIR synthesis starts soon after strand invasion, progresses slower than S-phase replication, and requires primase for stabilization of the nascent leading strand. DNA synthesis can initiate in the absence of certain enzymes, but efficiency is compromised. Interstitial telomeric DNA and transcription can disrupt and suppress BIR initiation, leading to mutagenesis and chromosome rearrangements.
Article
Multidisciplinary Sciences
Mehran Ghafari, Justin Clark, Hao-Bo Guo, Ruofan Yu, Yu Sun, Weiwei Dang, Hong Qin
Summary: Microfluidic-based assays are effective in examining replicative aging of yeast cells, and deep learning can offer an efficient way to analyze a large number of images from these experiments. In this study, convolutional neural networks outperformed capsule networks in classifying time-lapse images of dividing yeast cells, with an ensemble of three models achieving the highest overall accuracy. Extending classification classes and data augmentation can further improve the predictions of biological categories.
Article
Multidisciplinary Sciences
Ruofan Yu, Xiaohua Cao, Luyang Sun, Jun-Yi Zhu, Brian M. Wasko, Wei Liu, Emeline Crutcher, Haiying Liu, Myeong Chan Jo, Lidong Qin, Matt Kaeberlein, Zhe Han, Weiwei Dang
Summary: Histone acetylations serve as important epigenetic markers that regulate transcriptional activation in response to metabolic changes and stresses. In this study, the inactivation of the HDA complex was found to activate longevity and confer resistance to stress through trehalose metabolism. This longevity effect is independent of the Cyc8-Tup1 repressor complex and is evolutionarily conserved.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Hao-Bo Guo, Mehran Ghafari, Weiwei Dang, Hong Qin
Summary: The study introduced a novel approach to characterize system-level changes in gene networks during replicative aging in Saccharomyces cerevisiae, revealing distinct roles of essential proteins and hub proteins in the age-dependent interaction potential landscapes. The findings suggest that hub proteins tend to avoid other hub proteins, while essential proteins prefer to interact with each other, shedding light on the uncoupling between protein and transcript levels during replicative aging.
SCIENTIFIC REPORTS
(2021)
Review
Biotechnology & Applied Microbiology
Brenna S. McCauley, Weiwei Dang
Summary: Cryptic transcription, a type of transcriptional dysregulation, is elevated during aging in mammalian stem cells. Increased cryptic transcription may have detrimental effects on stem cell function and other aging phenotypes.
BRIEFINGS IN FUNCTIONAL GENOMICS
(2022)
Article
Multidisciplinary Sciences
Michael Prattes, Irina Grishkovskaya, Victor-Valentin Hodirnau, Ingrid Roessler, Isabella Klein, Christina Hetzmannseder, Gertrude Zisser, Christian C. Gruber, Karl Gruber, David Haselbach, Helmut Bergler
Summary: The study presents the structure of AAA-ATPase Drg1 in complex with its specific inhibitor diazaborine, shedding light on the mechanism of inhibition and specificity of this type of inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Tanja Limberger, Michaela Schlederer, Karolina Trachtova, Ines Garces de los Fayos Alonso, Jiaye Yang, Sandra Hoegler, Christina Sternberg, Vojtech Bystry, Jan Oppelt, Boris Tichy, Margit Schmeidl, Petra Kodajova, Anton Jaeger, Heidi A. Neubauer, Monika Oberhuber, Belinda S. Schmalzbauer, Sarka Pospisilova, Helmut Dolznig, Wolfgang Wadsak, Zoran Culig, Suzanne D. Turner, Gerda Egger, Sabine Lagger, Lukas Kenner
Summary: This study reveals the functional consequences of truncation mutations of the KMT2C gene in prostate cancer, showing that these mutations drive proliferation and formation of PIN. Loss of both KMT2C and PTEN in prostate cancer leads to loss of senescence, metastatic dissemination, and reduced life expectancy. The study highlights the prognostic significance of KMT2C mutation status and suggests MYC signalling axis inhibition as a potential treatment option for patients with KMT2C truncations and poor prognosis.
Article
Cell Biology
Jan Futas, Jan Oppelt, Leona Vychodilova, Pamela Burger, Petr Horin
Summary: Natural killer cells and cytotoxic T lymphocytes are important cell populations in the immune system that can directly kill target cells. Different mammalian species may have differences in their pore-forming protein and granule-bound serine proteases. This study characterizes the genes PRF1, GZMA, and GZMB in 17 felid species and finds high similarities between these genes in felids. Phylogenetic analysis shows that the genes correspond to the zoological taxonomy of the Felidae, except GZMA. No positive selection effects were found in the studied genes, but purifying selection effects were observed for PRF1 and GZMA.
Article
Infectious Diseases
Eliska Vrbova, Angel A. Noda, Linda Grillova, Islay Rodriguez, Allyn Forsyth, Jan Oppelt, David Smajs
Summary: Bejel is a neglected non-venereal disease caused by Treponema pallidum subsp. endemicum (TEN). This study sequenced and analyzed TEN isolates obtained from syphilis patients in Cuba, a non-endemic area for bejel. The results suggest a persistent infection in the Cuban population rather than a single outbreak caused by imported cases.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Biology
Enrico F. Semeraro, Lisa Marx, Johannes Mandl, Ilse Letofsky-Papst, Claudia Mayrhofer, Moritz P. K. Frewein, Haden L. Scott, Sylvain Prevost, Helmut Bergler, Karl Lohner, Georg Pabst
Summary: This study investigated the real-time response of Escherichia coli to lactoferricin-derived antimicrobial peptides (AMPs) using millisecond time-resolved synchrotron small-angle X-ray scattering. The results showed that the AMPs quickly permeabilize the cytosolic membrane, blocking important physiological processes and causing bacterial death. Additionally, even at sublethal peptide concentrations, damage and leakage of the cell envelope were observed. The most efficient AMP studied outperformed others in terms of membrane permeabilization speed and the lowest intracellular peptide concentration required to inhibit bacterial growth.
Article
Biochemistry & Molecular Biology
Michael Prattes, Irina Grishkovskaya, Victor-Valentin Hodirnau, Christina Hetzmannseder, Gertrude Zisser, Carolin Sailer, Vasileios Kargas, Mathias Loibl, Magdalena Gerhalter, Lisa Kofler, Alan J. Warren, Florian Stengel, David Haselbach, Helmut Bergler
Summary: The study reveals the molecular mechanism of Rlp24 release by Drg1 from pre-60S ribosomal particles, highlighting the involvement of Arx1 and rRNA expansion segment ES27 in substrate positioning and extraction. This provides important insights into the conserved modus operandi of AAA-ATPases.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Jana Bubenikova, Jan Futas, Jan Oppelt, Martin Plasil, Roman Vodicka, Pamela A. Burger, Petr Horin
Summary: Natural killer (NK) cells are important components of the innate immune system and are regulated by natural killer cell receptors. We studied the NCR1, NCR2, and NCR3 genes in different species of Felidae and found that they were present and conserved in all species. The phylogenetic analysis showed that NCR1 and NCR2 corresponded to the current zoological taxonomy, with some exceptions. NCR3 sequences were highly conserved and did not provide clear phylogenetic information. NCR2 showed the highest level of diversity both between species and within species.
Article
Cell Biology
Martin Plasil, Jan Oppelt, Marie Klumplerova, Jana Bubenikova, Leona Vychodilova, Eva Janova, Karla Stejskalova, Jan Futas, Ales Knoll, Agnes Leblond, Andrei D. Mihalca, Petr Horin
Summary: The major histocompatibility complex (MHC) includes class I and II genes that are vital for immune response against pathogens. These genes exhibit high levels of single nucleotide polymorphisms (SNPs) in exons encoding antigen binding sites. This study aimed to investigate the variability of MHC genes, particularly MHC class I physical haplotypes. Using long-range next-generation sequencing, alleles in exon 2 and exon 3 were identified in three genetically distinct horse breeds. A total of 116 allelic variants were found in the MHC class I genes, with 112 being novel. Extensive variability in the MHC region was confirmed, and diversifying and purifying selection were detected in the analyzed MHC class I and II loci.
Editorial Material
Genetics & Heredity
Brenna S. Mccauley, Weiwei Dang
Summary: This study reveals the mechanisms underlying increased cryptic transcription during aging and senescence, identifying cryptic transcription start sites and chromatin state changes that may contribute to this process.
TRENDS IN GENETICS
(2023)
Article
Geriatrics & Gerontology
An Yu, Ruofan Yu, Haiying Liu, Chenliang Ge, Weiwei Dang
Summary: Adipose tissue is an important endocrine organ that regulates metabolism, immune response, and aging in mammals. SIRT1 is a crucial regulator that negatively regulates adipogenic differentiation. Knocking out SIRT1 in mesenchymal stem cells causes defects in osteogenesis and loss of adipose tissue. Impairment of SIRT1 function in MSCs during adipogenic differentiation leads to significant defects and cellular senescence.