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1
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Guan C, Otchere A, Laskovs M, Papatheodorou I, Slack C. Genetic and Pharmacological Inhibition of Metabotropic Glutamate Receptor Signalling Extends Lifespan in Drosophila. Aging Cell 2025; 24:e14500. [PMID: 39943697 PMCID: PMC12073928 DOI: 10.1111/acel.14500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 01/10/2025] [Accepted: 01/14/2025] [Indexed: 05/15/2025] Open
Abstract
Invertebrate models have been instrumental in advancing our understanding of the molecular mechanisms of ageing. The isolation of single gene mutations that both extend lifespan and improve age-related health have identified potential targets for therapeutic intervention to alleviate age-related morbidity. Here, we find that genetic loss of function of the G protein-coupled metabotropic glutamate receptor (DmGluRA) in Drosophila extends the lifespan of female flies. This longevity phenotype was accompanied by lower basal levels of oxidative stress and improved stress tolerance, and differences in early-life behavioural markers. Gene expression changes in DmGluRA mutants identified reduced ribosome biogenesis, a hallmark of longevity, as a key process altered in these animals. We further show that the pro-longevity effects of reduced DmGluRA signalling are dependent on the fly homologue of Fragile X Mental Retardation Protein (FMRP), an important regulator of ribosomal protein translation. Importantly, we can recapitulate lifespan extension using a specific pharmacological inhibitor of mGluR activity. Hence, our study identifies metabotropic glutamate receptors as potential targets for age-related therapeutics.
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Affiliation(s)
- Cui Guan
- College of Health and Life SciencesAston UniversityBirminghamUK
- School of Life SciencesWarwick UniversityCoventryUK
| | - Abigail Otchere
- College of Health and Life SciencesAston UniversityBirminghamUK
| | - Mihails Laskovs
- College of Health and Life SciencesAston UniversityBirminghamUK
- School of Life SciencesWarwick UniversityCoventryUK
| | | | - Cathy Slack
- College of Health and Life SciencesAston UniversityBirminghamUK
- School of Life SciencesWarwick UniversityCoventryUK
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2
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Soto J, Pinilla F, Olguín P, Castañeda LE. Genetic Architecture of the Thermal Tolerance Landscape in Drosophila melanogaster. Mol Ecol 2025; 34:e17697. [PMID: 40035350 DOI: 10.1111/mec.17697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 12/27/2024] [Accepted: 02/04/2025] [Indexed: 03/05/2025]
Abstract
Increased environmental temperatures associated with global warming strongly impact natural populations of ectothermic species. Therefore, it is crucial to understand the genetic basis and evolutionary potential of heat tolerance. However, heat tolerance and its genetic components depend on the methodology, making it difficult to predict the adaptive responses to global warming. Here, we measured the knockdown time for 100 lines from the Drosophila Genetic Reference Panel (DGRP) at four different static temperatures, and we estimated their thermal-death-time (TDT) curves, which incorporate the magnitude and the time of exposure to thermal stress, to determine the genetic basis of the thermal tolerance landscape. Through quantitative genetic analyses, the knockdown time showed a significant heritability at different temperatures and that its genetic correlations decreased as temperatures differences increased. Significant genotype-by-sex and genotype-by-environment interactions were noted for heat tolerance. We also discovered genetic variability for the two parameters of TDT: CTmax and thermal sensitivity. Taking advantage of the DGRP, we performed a GWAS and identified multiple variants associated with the TDT parameters, which mapped to genes related to signalling and developmental functions. We performed functional validations for some candidate genes using RNAi, which revealed that genes such as mam, KNCQ, or robo3 affect the knockdown time at a specific temperature but are not associated with the TDT parameters. In conlusion, the thermal tolerance landscape display genetic variation and plastic responses, which may facilitate the adaptation of Drosophila populations to a changing world.
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Affiliation(s)
- Juan Soto
- Program of Human Genetics, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Francisco Pinilla
- Program of Human Genetics, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Patricio Olguín
- Program of Human Genetics, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
- Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Luis E Castañeda
- Program of Human Genetics, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
- Research Ring in Pest Insects and Climate Change (PIC2), Santiago, Chile
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3
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Even-Ros D, Huertas-Romero J, Marín-Menguiano M, Nusspaumer G, Borge M, Irimia M, Zurita F, González-Reyes A. Drosophila ovarian stem cell niche ageing involves coordinated changes in transcription and alternative splicing. Nat Commun 2025; 16:2596. [PMID: 40091053 PMCID: PMC11911433 DOI: 10.1038/s41467-025-57901-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 03/06/2025] [Indexed: 03/19/2025] Open
Abstract
Gene expression (GE) and alternative splicing (AS) contribute to the formation of new interaction networks with potentially significant cellular functions. Here, we investigate ageing in the Drosophila female germline stem cell (GSC) niche and describe functional changes in both GE and AS. The GSC niche comprises three types of support cells, whose ageing transcriptomes reveal differential GE and AS variations related to cell adhesion, cytoskeleton and neural signalling. Because each population show distinctive GE and AS changes, niche cell types possess unique ageing signatures. Depending on the cell population, groups of genes display changes in both GE and AS, revealing a coordinated regulation of transcription and splicing during niche ageing. One such gene is Fasciclin 2, a neural adhesion molecule that we find is essential for niche functioning. Furthermore, genes involved in AS undergo changes in GE and/or AS themselves, providing a mechanistic explanation for the coordination of these two processes during niche ageing. This is the case of the splicing factor Smu1, described here as a key element necessary for ovarian niche homeostasis.
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Affiliation(s)
- Dilamm Even-Ros
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Junta de Andalucía-UPO, Carretera de Utrera km 1, 41013, Seville, Spain
| | - Judit Huertas-Romero
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Junta de Andalucía-UPO, Carretera de Utrera km 1, 41013, Seville, Spain
| | - Miriam Marín-Menguiano
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Junta de Andalucía-UPO, Carretera de Utrera km 1, 41013, Seville, Spain
| | - Gretel Nusspaumer
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Junta de Andalucía-UPO, Carretera de Utrera km 1, 41013, Seville, Spain
| | - Miguel Borge
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
| | - Manuel Irimia
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- ICREA, Barcelona, Spain
| | - Federico Zurita
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, Centro de Investigación Biomédica, 18071, Granada, Spain.
| | - Acaimo González-Reyes
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Junta de Andalucía-UPO, Carretera de Utrera km 1, 41013, Seville, Spain.
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Zhao X, Dong Q, Zhu H, Ding Y, Deng D, Miao H, Tan Y, Ge L. Methuselah-like 2 mediated 20-hydroxyecdysone (20E) signaling regulates molting and fecundity in Nilaparvata lugens (Stål) (Hemiptera: Delphacidae). PEST MANAGEMENT SCIENCE 2025. [PMID: 39980407 DOI: 10.1002/ps.8722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/13/2025] [Accepted: 02/05/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND G protein-coupled receptors (GPCRs) are very promising as the targets of endogenous neuropeptides/neuromodulators that, upon binding to receptors, induce profound changes in insect physiology. The Methuselan/Methuselan-like subfamily of GPCRs is reported to be associated with longevity and stress resistance. A previous study showed the fungicide jingangmycin-induced expression of Mthl2 and enhanced stress resistance in Nilaparvata lugens. However, the other physiological functions of Mthl2 remain unelucidated. RESULTS The Mthl2 was highly expressed before molting and decreased after that until the next ecdysis, showing a cyclical pattern related to molting behavior and predominantly distributed in cuticle-producing and reproductive tissues in N. lugens. Silencing Mthl2 by RNAi in nymphs disrupted the synthesis of 20E, caused downregulation of the 20E signaling-related genes, and further affected the transcription of cuticular proteins. Moreover, it led to the malformation of the integument structure and a declined emergence rate, whereas exogenous 20E could rescue the declined emergence rate caused by knockdown of Mthl2. Furthermore, depletion of Mthl2 through RNAi in the N. lugens nymphal stage influenced the development of the ovaries and fecundity in female adults. The soluble protein content in reproductive tissues, the protein and transcript levels of Vitellogenin (Vg) were significantly decreased after silencing of Mthl2, ultimately leading to a decline in the number of offspring with an obviously transgenerational consequence. CONCLUSION The current study revealed the physiological functions of Mthl2 in molting and fecundity of N. lugens, which can be used as an RNAi-based insecticide discovery to control this pest. © 2025 Society of Chemical Industry.
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Affiliation(s)
- Xudong Zhao
- College of Plant Protection, Yangzhou University, Yangzhou, China
| | - Qiaoqiao Dong
- College of Plant Protection, Yangzhou University, Yangzhou, China
| | - Haowen Zhu
- College of Plant Protection, Yangzhou University, Yangzhou, China
| | - Yuting Ding
- College of Plant Protection, Yangzhou University, Yangzhou, China
| | - Di Deng
- College of Plant Protection, Yangzhou University, Yangzhou, China
| | - Hong Miao
- College of Mechanical Engineering, Yangzhou University, Yangzhou, China
| | - Yongan Tan
- Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, China
| | - LinQuan Ge
- College of Plant Protection, Yangzhou University, Yangzhou, China
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Zhang C, Wang J, Yao T, Hu J, Sun F, Feng C, Sun Z, Shao Y, Wang Z, Wu J, Huang Y. Proteomic analysis across aged tissues reveals distinct signatures and the crucial involvement of midgut barrier function in the regulation of aging. Aging Cell 2025; 24:e14344. [PMID: 39319447 PMCID: PMC11709110 DOI: 10.1111/acel.14344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 08/06/2024] [Accepted: 08/28/2024] [Indexed: 09/26/2024] Open
Abstract
The process of aging is a natural phenomenon characterized by gradual deterioration in biological functions and systemic homeostasis, which can be modulated by both genetic and environmental factors. Numerous investigations conducted on model organisms, including nematodes, flies, and mice, have elucidated several pivotal aging pathways, such as insulin signaling and AMPK signaling. However, it remains uncertain whether the regulation of the aging process is uniform or diverse across different tissues and whether manipulating the same aging factor can result in consistent outcomes in various tissues. In this study, we utilize the Drosophila organism to investigate tissue-specific proteome signatures during the aging process. Although distinct proteins undergo changes in aged tissues, certain common altered functional networks are constituently identified across different tissues, including the decline of the mitochondrial ribosomal network, autophagic network, and anti-ROS defense networks. Furthermore, downregulation of insulin receptor (InR) in the midguts, muscle, and central nervous system (CNS) of flies leads to a significant extension in fly lifespans. Notably, despite manipulating the same aging gene InR, diverse alterations in proteins are observed across different tissues. Importantly, knockdown of InR in the midguts leads to a distinct proteome compared with other tissues, resulting in enhanced actin nucleation and glutathione metabolism, while attenuating age-related elevation of serine proteases. Consequently, knockdown of InR results in rejuvenation of the integrity of the midgut barrier and augmentation of anti-ROS defense capabilities. Our findings suggest that the barrier function of the midgut plays a pivotal role in defending against aging, underscoring the paramount importance of maintaining optimal gut physiology to effectively delay the aging process. Moreover, when considering age-related changes across various tissues, it is more reasonable to identify functional networks rather than focusing solely on individual proteins.
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Affiliation(s)
- Congying Zhang
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Jinlong Wang
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Tianzhao Yao
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Jiaxin Hu
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Feifei Sun
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Chunlu Feng
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Zhendong Sun
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Yuzhuo Shao
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Zhu Wang
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
| | - Jiarui Wu
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
- Key Laboratory of Systems Biology, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences, Chinese Academy of SciencesHangzhouChina
| | - Yunpeng Huang
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina
- Key Laboratory of Systems Biology, Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences, Chinese Academy of SciencesHangzhouChina
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6
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Chaudhari PS, Ermolaeva MA. Too old for healthy aging? Exploring age limits of longevity treatments. NPJ METABOLIC HEALTH AND DISEASE 2024; 2:37. [PMID: 39678297 PMCID: PMC11638076 DOI: 10.1038/s44324-024-00040-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 11/13/2024] [Indexed: 12/17/2024]
Abstract
It is well documented that aging elicits metabolic failures, while poor metabolism contributes to accelerated aging. Metabolism in general, and energy metabolism in particular are also effective entry points for interventions that extend lifespan and improve organ function during aging. In this review, we discuss common metabolic remedies for healthy aging from the angle of their potential age-specificity. We demonstrate that some well-known metabolic treatments are mostly effective in young and middle-aged organisms, while others maintain high efficacy independently of age. The mechanistic basis of presence or lack of the age limitations is laid out and discussed.
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Affiliation(s)
| | - Maria A. Ermolaeva
- Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745 Jena, Germany
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7
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Zhu Y, Wang M, Zhu J, Zhang X, Ye X, Chen J. Protective effects of Chinese bayberry pomace wine against oxidative stress on Drosophila melanogaster. Food Res Int 2024; 194:114885. [PMID: 39232523 DOI: 10.1016/j.foodres.2024.114885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/22/2024] [Accepted: 08/08/2024] [Indexed: 09/06/2024]
Abstract
The Chinese bayberry pomace wine (CPW) was prepared with the assisted fermentation of lactic acid bacteria and acetic acid bacteria, and its antioxidant effect on Drosophila melanogaster was researched. After mixed fermentation, CPW had a better color, which means there was more retention of anthocyanins, and the functional activity of anthocyanins could enhance the antioxidant capacity of flies. We found that the lifespan of flies exposed to CPW was prolonged, and the reproductive capacity of these flies was decreased. The food intake of flies was also influenced by CPW with gender differences. Furthermore, CPW alleviated the excessive proliferation of the intestinal precursor cells of H2O2-induced flies and activated the transcription level of antibacterial peptide genes. CPW had a protective effect on H2O2-induced acute injury flies, with an increased survival rate, enhanced SOD and CAT activities, and decreased malondialdehyde (MDA) content in flies. The expression of oxidative stress-related genes including CuZn-SOD, Mn-SOD, and CAT was also significantly upregulated by CPW, but the downregulation effect of CPW on age-related gene expression such as methuselah (MTH), the target of rapamycin (TOR) and ribosomaiprotein S6 kinase (S6K) was sex-specific. These results suggested that CPW played an important role in anti-oxidative stress injury, which was beneficial to promoting the reuse of by-products from Chinese bayberry processing.
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Affiliation(s)
- Yanyun Zhu
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Zhejiang University, China; Zhejiang University Zhongyuan Institute, Zhengzhou 450001, China
| | - Mengting Wang
- NingboTech University, Qianhunan Road 1, Ningbo, Zhejiang Province, China.
| | - Jingjing Zhu
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Zhejiang University, China
| | - Xiayin Zhang
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Zhejiang University, China
| | - Xingqian Ye
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Zhejiang University, China
| | - Jianchu Chen
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Zhejiang University, China.
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8
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Huang S, Cox RL, Tuckowski A, Beydoun S, Bhat A, Howington MB, Sarker M, Miller H, Ruwe E, Wang E, Li X, Gardea EA, DeNicola D, Peterson W, Carrier JM, Miller RA, Sutphin GL, Leiser SF. Fmo induction as a tool to screen for pro-longevity drugs. GeroScience 2024; 46:4689-4706. [PMID: 38787463 PMCID: PMC11335711 DOI: 10.1007/s11357-024-01207-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 05/15/2024] [Indexed: 05/25/2024] Open
Abstract
Dietary restriction (DR) and hypoxia (low oxygen) extend lifespan in Caenorhabditis elegans through the induction of a convergent downstream longevity gene, fmo-2. Flavin-containing monooxygenases (FMOs) are highly conserved xenobiotic-metabolizing enzymes with a clear role in promoting longevity in nematodes and a plausible similar role in mammals. This makes them an attractive potential target of small molecule drugs to stimulate the health-promoting effects of longevity pathways. Here, we utilize an fmo-2 fluorescent transcriptional reporter in C. elegans to screen a set of 80 compounds previously shown to improve stress resistance in mouse fibroblasts. Our data show that 19 compounds significantly induce fmo-2, and 10 of the compounds induce fmo-2 more than twofold. Interestingly, 9 of the 10 high fmo-2 inducers also extend lifespan in C. elegans. Two of these drugs, mitochondrial respiration chain complex inhibitors, interact with the hypoxia pathway to induce fmo-2, whereas two dopamine receptor type 2 (DRD2) antagonists interact with the DR pathway to induce fmo-2, indicating that dopamine signaling is involved in DR-mediated fmo-2 induction. Together, our data identify nine drugs that each (1) increase stress resistance in mouse fibroblasts, (2) induce fmo-2 in C. elegans, and (3) extend nematode lifespan, some through known longevity pathways. These results define fmo-2 induction as a viable approach to identifying and understanding mechanisms of putative longevity compounds.
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Affiliation(s)
- Shijiao Huang
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
| | - Rebecca L Cox
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Angela Tuckowski
- Cell and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Safa Beydoun
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Ajay Bhat
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Marshall B Howington
- Cell and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Marjana Sarker
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Hillary Miller
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Ethan Ruwe
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Emily Wang
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Xinna Li
- Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 316048109-2200, USA
| | - Emily A Gardea
- Department of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA
| | - Destiny DeNicola
- Department of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA
| | - William Peterson
- Department of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA
| | - Jeffrey M Carrier
- Department of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA
| | - Richard A Miller
- Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 316048109-2200, USA
- University of Michigan Geriatrics Center, Ann Arbor, MI, 48109, USA
| | - George L Sutphin
- Department of Molecular & Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA
| | - Scott F Leiser
- Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
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9
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Harper JM, Hicks M, Jiménez AG. The resistance of domestic canine skin-derived fibroblasts to oxidative and non-oxidative chemical injury: implications of breed and body size. GeroScience 2024:10.1007/s11357-024-01358-y. [PMID: 39316259 DOI: 10.1007/s11357-024-01358-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/13/2024] [Indexed: 09/25/2024] Open
Abstract
Small-breed dogs live significantly longer lives than large-breed dogs, while having higher mass-specific metabolic rates and faster growth rates. Underlying this observed physiological difference across domestic dogs, there must also be differences at other levels of organization that could lead to elucidating what accounts for the disparity in aging rates and life span within this species. At the cellular level, a clear mechanism underlying whole animal traits has not been fully elucidated. Here, we cultured dermal fibroblasts from large and small breed dogs from both young and old age categories and examined the degree of resistance to multiple sources of cytotoxic stress. This included heat (42 °C), paraquat, cadmium, and hydrogen peroxide for increasing amounts of time (heat) or increasing concentrations (chemical stressors). We hypothesized that small breed dogs, with longer lifespans, would have greater cellular resistance to stress compared with large breed dogs. Final sample sizes include small puppies (N = 18), large puppy (N = 32), small old (N = 11), and large old (N = 23) dogs. Using a 2 (donor size) by 2 (donor age) between-subjects multivariate analysis of variance, we found that the values for the dose that killed 50% of the cells (LD50) were not significantly different based on donor size (p = 0.45) or donor age (p = 0.20). The interaction was also not significant (p = 0.47). Interestingly, we did find that the degree of resistance to cadmium toxicity was significantly correlated with the degree of resistance to both heat and hydrogen peroxide, but not paraquat (p < 0.01 for both). These data suggest that cellular stress resistance does not differ among domestic dogs as a function of size or age, pointing to other cellular pathways as the mechanistic basis for the observed differences in lifespan.
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Affiliation(s)
- James M Harper
- Department of Biological Sciences, Sam Houston State University, Huntsville, TX, 77341, USA.
| | - Megan Hicks
- Department of Biological Sciences, Sam Houston State University, Huntsville, TX, 77341, USA
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10
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Krittika S, Yadav P. Correlated changes in stress resistance and biochemical parameters in response to long-term protein restriction in Drosophila melanogaster. ROYAL SOCIETY OPEN SCIENCE 2024; 11:231741. [PMID: 39100164 PMCID: PMC11295984 DOI: 10.1098/rsos.231741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 05/02/2024] [Indexed: 08/06/2024]
Abstract
Studies in fruit flies, Drosophila melanogaster, have observed considerable variation in the effect of dietary protein restriction (PR) on various fitness traits. In addition, not only are there inconsistent results relating lifespan to stress resistance, but also the long-term effects of PR are unexplored. We study PR implementation across generations (long term) hypothesizing that it will be beneficial for fitness traits, stress resistance and storage reserves due to nutritional plasticity transferred by parents to offspring in earlier Drosophila studies. By imposing two concentrations of PR diets (50% and 70% of control protein) from the pre-adult and adult (age 1 day) stages of the flies, we assessed the stage-specific and long-term effect of the imposed PR. All long-term PR flies showed increased resistance against the tested stressors (starvation, desiccation, H2O2-induced oxidative stress). In addition, we also found long-term PR-induced increased stress resistance across generations. The PR flies also possessed higher protein and triglyceride (TG) content, reduced glucose and unaffected glycogen levels. We also assayed the effect of returning the PR flies to control (AL) food for a single generation and assessed their biochemical parameters to witness the transient PR effect. It was seen that TG content upon reversal was similar to AL flies except for PRI70 males; however, the glucose levels of PR males increased, while they were consistently lower in females. Taken altogether, our study suggests that long-term PR implementation contributes to increased stress resistance and was found to influence storage reserves in D. melanogaster.
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Affiliation(s)
- Sudhakar Krittika
- Fly Laboratory # 210, Anusandhan Kendra-II, School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu 613401, India
| | - Pankaj Yadav
- Fly Laboratory # 210, Anusandhan Kendra-II, School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu 613401, India
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11
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Lotfy M, Khattab A, Shata M, Alhasbani A, Almesmari A, Alsaeedi S, Alyassi S, Kundu B. Destructive effects of UVC radiation on Drosophila melanogaster: Mortality, fertility, mutations, and molecular mechanisms. PLoS One 2024; 19:e0303115. [PMID: 38776353 PMCID: PMC11111075 DOI: 10.1371/journal.pone.0303115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 04/09/2024] [Indexed: 05/24/2024] Open
Abstract
The detrimental effects of ultraviolet C (UVC) radiation on living organisms, with a specific focus on the fruit fly Drosophila melanogaster, were examined. This study investigated the impact of heightened UVC radiation exposure on D. melanogaster by assessing mortality and fertility rates, studying phenotypic mutations, and investigating the associated molecular mechanisms. The findings of this study revealed that UVC radiation increases mortality rates and decreases fertility rates in D. melanogaster. Additionally, phenotypic wing mutations were observed in the exposed flies. Furthermore, the study demonstrated that UVC radiation downregulates the expression of antioxidant genes, including superoxide dismutase (SOD), manganese-dependent superoxide dismutase (Mn-SOD), zinc-dependent superoxide dismutase (Cu-Zn-SOD), and the G protein-coupled receptor methuselah (MTH) gene. These results suggest that UVC radiation exerts a destructive effect on D. melanogaster by inducing oxidative stress, which is marked by the overexpression of harmful oxidative processes and a simultaneous reduction in antioxidant gene expression. In conclusion, this study underscores the critical importance of comprehending the deleterious effects of UVC radiation, not only to safeguard human health on Earth, but also to address the potential risks associated with space missions, such as the ongoing Emirate astronaut program.
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Affiliation(s)
- Mohamed Lotfy
- Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Aalaa Khattab
- Faculty of Dentistry, The British University in Egypt, El Sherouk City, Cairo, Egypt
| | - Mohammed Shata
- Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Ahmad Alhasbani
- Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Abdulla Almesmari
- Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Saeed Alsaeedi
- Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Saeed Alyassi
- Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Biduth Kundu
- Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
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12
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Zhu X, Guo C, Xu S, Lv F, Guo Z, Lin S, Yang C, Deng Z, Chen S, Huang Y, Zhao Z, Li L. Clinical distribution of carbapenem genotypes and resistance to ceftazidime-avibactam in Enterobacteriaceae bacteria. Front Cell Infect Microbiol 2024; 14:1345935. [PMID: 38572315 PMCID: PMC10987847 DOI: 10.3389/fcimb.2024.1345935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 03/08/2024] [Indexed: 04/05/2024] Open
Abstract
Introduction Bacterial resistance is a major threat to public health worldwide. To gain an understanding of the clinical infection distribution, drug resistance information, and genotype of CRE in Dongguan, China, as well as the resistance of relevant genotypes to CAZ-AVI, this research aims to improve drug resistance monitoring information in Dongguan and provide a reliable basis for the clinical control and treatment of CRE infection. Methods VITEK-2 Compact automatic analyzer was utilized to identify 516 strains of CRE collected from January 2017 to June 2023. To determine drug sensitivity, the K-B method, E-test, and MIC methods were used. From June 2022 to June 2023, 80 CRE strains were selected, and GeneXpert Carba-R was used to detect and identify the genotype of the carbapenemase present in the collected CRE strains. An in-depth analysis was conducted on the CAZ-AVI in vitro drug sensitivity activity of various genotypes of CRE, and the results were statistically evaluated using SPSS 23.0 and WHONET 5.6 software. Results This study identified 516 CRE strains, with the majority (70.16%) being K.pneumoniae, followed by E.coli (18.99%). Respiratory specimens had highest detection rate with 53.77% identified, whereas urine specimens had the second highest detection rate with 17.99%. From June 2022 to June 2023, 95% of the strains tested using the CRE GeneXpert Carba-R assay possessed carbapenemase genes, of which 32.5% were blaNDM strains and 61.25% blaKPC strains. The results showed that CRE strains containing blaKPC had a significantly higher rate of resistance to amikacin, cefepime, and aztreonam than those harboring blaNDM. Conclusions The CRE strains isolated from Dongguan region demonstrated a high resistance rate to various antibiotics used in clinical practice but a low resistance rate to tigecycline. These strains produce Class A serine carbapenemases and Class B metals β-lactamases, with the majority of them carrying blaNDM and blaKPC. Notably, CRE strains with blaKPC and blaNDM had significantly lower resistance rates to tigecycline. CAZ-AVI showed a good sensitivity rate with no resistance to CRE strains carrying blaKPC. Therefore, CAZ-AVI and tigecycline should be used as a guide for rational use of antibiotics in clinical practice to effectively treat CRE.
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Affiliation(s)
- Xueyun Zhu
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
- Department of Laboratory Medicine, Dongguan Kanghua Hospital, Dongguan, China
| | - Caixia Guo
- The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shengxi Xu
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Fei Lv
- Department of Laboratory Medicine, Dongguan Songshan Lake Tungwah Hospital, Dongguan, China
| | - Zhusheng Guo
- Department of Laboratory Medicine, Dongguan Songshan Lake Tungwah Hospital, Dongguan, China
| | - Sisi Lin
- Department of Laboratory Medicine, Dongguan Songshan Lake Tungwah Hospital, Dongguan, China
| | - CongZhu Yang
- Department of Laboratory Medicine, Dongguan Songshan Lake Tungwah Hospital, Dongguan, China
| | - Zhuliang Deng
- Department of Laboratory Medicine, Dongguan Songshan Lake Tungwah Hospital, Dongguan, China
| | - Shaofeng Chen
- Department of Laboratory Medicine, Dongguan Songshan Lake Tungwah Hospital, Dongguan, China
| | - Ya Huang
- Department of Laboratory Medicine, Dongguan Songshan Lake Tungwah Hospital, Dongguan, China
| | - Zuguo Zhao
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Lu Li
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
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13
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Chen L, Liang J, Zhang Q, Yang C, Lu H, Zhang R, Chen K, Wang S, Li M, Zhang S, He N. Mulberry-derived miR168a downregulates BmMthl1 to promote physical development and fecundity in silkworms. Int J Biol Macromol 2024; 259:129077. [PMID: 38199542 DOI: 10.1016/j.ijbiomac.2023.129077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/14/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024]
Abstract
Plant-derived miRNAs and their interactions with host organisms are considered important factors in regulating host physiological processes. In this study, we investigated the interaction between the silkworm, an oligophagous insect, and its primary food source, mulberry, to determine whether mulberry-derived miRNAs can penetrate silkworm cells and regulate their functions. Our results demonstrated that miR168a from mulberry leaves enters the silkworm hemolymph and binds to the silkworm Argonaute1 BmAGO1, which is transported via vesicles secreted by silkworm cells to exert its regulatory functions. In vivo and in vitro functional studies revealed that miR168a targets the mRNA of silkworm G protein-coupled receptor, BmMthl1, thereby inhibiting its expression and activating the JNK-FoxO pathway. This activation reduces oxidative stress responses, prolongs the lifespan of silkworms, and improves their reproductive capacity. These findings highlight the challenges of replacing mulberry leaves with alternative protein sources and provide a foundation for developing silkworm germplasms suitable for factory rearing.
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Affiliation(s)
- Lin Chen
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Jiubo Liang
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Qi Zhang
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Chao Yang
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Hulin Lu
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Renze Zhang
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Kaiying Chen
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Sheng Wang
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Mingbo Li
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Shaoyu Zhang
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
| | - Ningjia He
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, China.
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Murthy MN, Shyamala BV. Ashwagandha- Withania somnifera (L.) Dunal as a multipotent neuroprotective remedy for genetically induced motor dysfunction and cellular toxicity in human neurodegenerative disease models of Drosophila. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:116897. [PMID: 37442493 DOI: 10.1016/j.jep.2023.116897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/25/2023] [Accepted: 07/08/2023] [Indexed: 07/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ashwagandha-Withania somnifera (L.) Dunal, well known for its multipotent therapeutic properties has been used in Ayurveda for 3000 years. The plant with more than 50 active phytoconstituents is recognised for its anti-cancerous, anti-diabetic, anti-inflammatory, anti-microbial, and neurotherapeutic properties demonstrated in in vitro studies and chemically induced rodent models. Genetically targeted Parkinson's, Alzheimer's and other neurodegenerative disease models have been created in Drosophila and have been used to get mechanistic insight into the in vivo cellular events, and genetic pathways that underlie respective neurodegenerative condition. But hitherto, there aren't enough attempts made to capitalize the genetic potential of these disease models to validate the therapeutic efficacy of different reagents used in traditional medicine, in the context of specific disease-causing genetic mutations. AIM OF THE STUDY Drugs discovered using in vitro platforms might fail in several instances of clinical trials because of the genetic heterogeneity and variability in the physiological context found among the patients. Drosophila by virtue of its genetically regulated experimental potential forms an ideal in vivo model to validate the candidate reagents discovered in in vitro screens for their efficacy under specific genetic situations. Here we have used genetically induced α-synucleinopathy and tauopathy transgenic fly models to study the efficacy of Ashwagandha treatment, assessing cellular and behavioural parameters. METHODS We have expressed the disease-causing human gene mutations in specific cell types of Drosophila using GAL4/UAS targeted expression system to create disease models. Human α-synuclein mutant (A30P) was expressed in dopaminergic neurons using Ddc-GAL4 driver strain to induce dopaminergic neurodegeneration and assayed for motor dysfunction. Human TauE14, mutant protein was expressed in photoreceptor neurons using GMR-GAL4 driver to induce photoreceptor degeneration. Microtubular destability and mitotic arrest in the dividing photoreceptor precursor cells were studied using αPH3 antibody. Lysosomal dysregulation caused necrotic black spots were induced by TauE14 with GMR-GAL4 driver, in a white mutant background. These flies mimicking neurodegenerative conditions were supplemented with different concentrations of Ashwagandha aqueous root extract mixed with regular fly food. The treated flies were analysed for cellular and behaviour parameters. RESULTS Lifespan assay shows that, Ashwagandha-root extract imparts an extended lifespan in male Drosophila flies which are intrinsically less stress resistant. Motor dysfunction caused due to human α-synuclein mutant protein expressed in dopaminergic neurons is greatly brought down. Further, Ashwagandha extract treatment significantly reduces TauE14 induced microtubular destability, mitotic arrest and neuronal death in photoreceptor neurons. Our experiment with tauopathy model in white mutant background exemplify that, Ashwagandha-root extract treatment can bring down lysosomal dysregulation induced necrosis of photoreceptor neurons. CONCLUSION We have carried out a multifaceted study which elucidates that Ashwagandha can serve as a comprehensive, phytotherapeutic formulation to combat neurodegeneration, targeting multiple causative genetically defective conditions.
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Affiliation(s)
- Mamatha Nagamadhu Murthy
- Developmental Genetics Laboratory, Department of Studies in Zoology, University of Mysore, Mysuru, 570006, India.
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15
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Liu YX, Hu C, Li YT, Gao P, Yang XQ. Identification of G Protein-Coupled Receptors (GPCRs) Associated with Lambda-Cyhalothrin Detoxification in Cydia pomonella. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:363-377. [PMID: 38134348 DOI: 10.1021/acs.jafc.3c06522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2023]
Abstract
While previous studies have reported G protein-coupled receptor (GPCR)-mediated insecticide resistance in various arthropods, the understanding of GPCR-associated resistance mechanisms in Cydia pomonella remains limited. In this study, a total of 95 CpGPCR genes categorized into four families were identified in C. pomonella. Results revealed high expression levels of the majority of the CpGPCRs during the first larval stage and in the head of C. pomonella. Exposure to lambda-cyhalothrin significantly increased the expression of 15 CpGPCRs, including CpGPCR70, which is highly expressed in all larval stages and shows the highest expression in the midgut. RNA interference (RNAi) demonstrated that downregulation of CpGPCR70 leads to reduced expression of key resistance-related genes and a decreased tolerance of larvae to lambda-cyhalothrin. These findings indicate that CpGPCR70 plays a crucial role in regulating the expression of detoxifying genes involved in lambda-cyhalothrin resistance, offering valuable insights for the development of more effective pest control strategies.
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Affiliation(s)
- Yu-Xi Liu
- College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, Liaoning, China
- Key Laboratory of Economical and Applied Entomology of Liaoning Province, Shenyang 110866, Liaoning, China
| | - Chao Hu
- College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, Liaoning, China
- Key Laboratory of Economical and Applied Entomology of Liaoning Province, Shenyang 110866, Liaoning, China
| | - Yu-Ting Li
- College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, Liaoning, China
- Key Laboratory of Economical and Applied Entomology of Liaoning Province, Shenyang 110866, Liaoning, China
| | - Ping Gao
- College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, Liaoning, China
- Key Laboratory of Economical and Applied Entomology of Liaoning Province, Shenyang 110866, Liaoning, China
| | - Xue-Qing Yang
- College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, Liaoning, China
- Key Laboratory of Economical and Applied Entomology of Liaoning Province, Shenyang 110866, Liaoning, China
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16
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Deng Z, Zhang X, Wolinska J, Blair D, Hu W, Yin M. Climate has contributed to population diversification of Daphnia galeata across Eurasia. Mol Ecol 2023; 32:5110-5124. [PMID: 37548328 DOI: 10.1111/mec.17094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/24/2023] [Accepted: 07/26/2023] [Indexed: 08/08/2023]
Abstract
Climate is a fundamental abiotic factor that plays a key role in driving the evolution, distribution and population diversification of species. However, there have been few investigations of genomic signatures of adaptation to local climatic conditions in cladocerans. Here, we have provided the first high-quality chromosome-level genome assembly (~143 Mb, scaffold N50 12.6 Mb) of the waterflea, Daphnia galeata, and investigated genomic variation in 22 populations from Central Europe and Eastern China. Our ecological-niche models suggested that the historic distribution of D. galeata in Eurasia was significantly affected by Quaternary climate fluctuations. We detected pronounced genomic and morphometric divergences between European and Chinese D. galeata populations. Such divergences could be partly explained by genomic signatures of thermal adaptation to distinct climate regimes: a set of candidate single-nucleotide polymorphisms (SNPs) potentially associated with climate were detected. These SNPs were in genes significantly enriched in the Gene ontology terms "determination of adult lifespan" and "translation repressor activity", and especially, mthl5 and SOD1 involved in the IIS pathway, and EIF4EBP2 involved in the target of the rapamycin signalling pathway. Our study indicates that certain alleles might be associated with particular temperature regimes, playing a functional role in shaping the population structure of D. galeata at a large geographical scale. These results highlight the potential role of molecular variation in the response to climate variation, in the context of global climate change.
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Affiliation(s)
- Zhixiong Deng
- MOE Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Science, Fudan University, Shanghai, China
| | - Xiuping Zhang
- MOE Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Science, Fudan University, Shanghai, China
| | - Justyna Wolinska
- Department of Evolutionary and Integrative Ecology, Leibniz Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany
- Department of Biology, Chemistry, Pharmacy, Institute of Biology, Freie Universität Berlin, Berlin, Germany
| | - David Blair
- College of Marine and Environmental Sciences, James Cook University, Townsville, Queensland, Australia
| | - Wei Hu
- MOE Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Science, Fudan University, Shanghai, China
| | - Mingbo Yin
- MOE Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Science, Fudan University, Shanghai, China
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17
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Awde DN, Řeřicha M, Knapp M. Increased pupal temperature has reversible effects on thermal performance and irreversible effects on immune system and fecundity in adult ladybirds. Commun Biol 2023; 6:838. [PMID: 37573399 PMCID: PMC10423239 DOI: 10.1038/s42003-023-05196-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 07/31/2023] [Indexed: 08/14/2023] Open
Abstract
The environmental conditions an organism encounters during development vary in their lasting impact on adult phenotypes. In the context of ongoing climate change, it is particularly relevant to understand how high developmental temperatures can impact adult traits, and whether these effects persist or diminish during adulthood. Here, we assessed the effects of pupal temperature (17 °C - normal temperature, 26 °C - increased temperature, or 35 °C - heat wave) on adult Harmonia axyridis thermal stress tolerance, immune function, starvation resistance, and fecundity. The temperature during pupation significantly affected all investigated traits in fresh adults. Heat acclimation decreased adult haemocyte concentration, cold tolerance, and total egg production, and had a positive effect on heat tolerance and starvation resistance. The negative effects of heat acclimation on cold tolerance diminished after seven days. In contrast, heat acclimation had a lasting positive effect on adult heat tolerance. Our results provide a broad assessment of the effects of developmental thermal acclimation on H. axyridis adult phenotypes. The relative plasticity of several adult traits after thermal acclimation may be consequential for the future geographic distribution and local performance of various insect species.
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Affiliation(s)
- David N Awde
- Department of Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00, Prague - Suchdol, Czech Republic
- Department of Biology, Faculty of Science, Mount Saint Vincent University, Halifax, NS, Canada
| | - Michal Řeřicha
- Department of Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00, Prague - Suchdol, Czech Republic
| | - Michal Knapp
- Department of Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00, Prague - Suchdol, Czech Republic.
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18
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Lin YC, Zhang M, Chang YJ, Kuo TH. Comparisons of lifespan and stress resistance between sexes in Drosophila melanogaster. Heliyon 2023; 9:e18178. [PMID: 37576293 PMCID: PMC10415617 DOI: 10.1016/j.heliyon.2023.e18178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/06/2023] [Accepted: 07/10/2023] [Indexed: 08/15/2023] Open
Abstract
Animals exhibit different extents of sexual dimorphism in a variety of phenotypes. Sex differences in longevity, one of the most complex life history traits, have also been reported. Although lifespan regulation has been studied extensively in the fruit fly, Drosophila melanogaster, the sex differences in lifespan have not been consistent in previous studies. To explore this issue, we revisited this question by examining the lifespan and stress resistance of both sexes among 15 inbred strains. We first found positive correlations between males and females from the same strain in terms of lifespan and resistance to starvation and desiccation stress. Although the lifespan difference between male and female flies varied greatly depending on the strain, males across all strains collectively had a longer lifespan. In contrast, females showed better resistance to starvation and desiccation stress. We also observed greater variation in lifespan and resistance to starvation and desiccation stress in females. Unexpectedly, there was no notable correlation observed between lifespan and the three types of stress resistance in either males or females. Overall, our study provides new data regarding sexual dimorphism in fly lifespan and stress resistance; this information may promote the investigation of mechanisms underlying longevity in future research.
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Affiliation(s)
- Yu-Chiao Lin
- Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu, Taiwan
| | - MingYang Zhang
- Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu, Taiwan
| | | | - Tsung-Han Kuo
- Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu, Taiwan
- Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan
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19
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Chen D, Lan X, Huang X, Huang J, Zhou X, Liu J, Hoffmann JA. mthl1, a potential Drosophila homologue of mammalian adhesion GPCRs, is involved in antitumor reactions to injected oncogenic cells in flies. Proc Natl Acad Sci U S A 2023; 120:e2303462120. [PMID: 37459549 PMCID: PMC10374174 DOI: 10.1073/pnas.2303462120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/18/2023] [Indexed: 07/20/2023] Open
Abstract
Injection of OCs into adult male flies induces a strong transcriptomic response in the host flies featuring in particular genes encoding bona fide G coupled proteins, among which the gene for methuselah like 1 is prominent. The injection is followed after a 3-d lag period, by the proliferation of the oncogenic cells. We hypothesized that through the product of mthl1 the host might control, at least in part, this proliferation as a defense reaction. Through a combination of genetic manipulations of the mthl1 gene (loss of function and overexpression of mthl1), we document that indeed this gene has an antiproliferative effect. Parallel injections of primary embryonic Drosophila cells or of various microbes do not exhibit this effect. We further show that mthl1 controls the expression of a large number of genes coding for chemoreceptors and genes implicated in regulation of development. Of great potential interest is our observation that the expression of the mouse gene coding for the adhesion G-protein-coupled receptor E1 (Adgre1, also known as F4/80), a potential mammalian homologue of mthl1, is significantly induced by B16-F10 melanoma cell inoculation 3 d postinjection in both the bone marrow and spleen (nests of immature and mature myeloid-derived immune cells), respectively. This observation is compatible with a role of this GPCR in the early response to injected tumor cells in mice.
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Affiliation(s)
- Di Chen
- Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou511436, China
| | - Xiao Lan
- Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou511436, China
| | - Xiaoming Huang
- Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou511436, China
| | - Jieqing Huang
- Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou511436, China
| | - Xiaojing Zhou
- Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou511436, China
| | - Jiyong Liu
- Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou511436, China
| | - Jules A. Hoffmann
- Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou511436, China
- University of StrasbourgInstitute for Advanced Study, 67000Strasbourg, France
- Institute of Molecular and Cellular Biology, CNRS, Insect Models of Innate Immunity (M3I; UPR9022), StrasbourgF-67084, France
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20
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Zhao L, Zhou J, Chen J, Zhang X, Zhang H, Guo L, Li D, Ning J, Wang X, Jin W, Mai K, Abraham E, Butcher R, Sun J. A chemical signal that promotes insect survival via thermogenesis. RESEARCH SQUARE 2023:rs.3.rs-2756320. [PMID: 37214941 PMCID: PMC10197781 DOI: 10.21203/rs.3.rs-2756320/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Cold-activated thermogenesis of brown adipose tissues (BAT) is vital for the survival of animals under cold stress and also inhibits the development of tumours. The development of small-molecule tools that target thermogenesis pathways could lead to novel therapies against cold, obesity, and even cancer. Here, we identify a chemical signal that is produced in beetles in the winter to activate fat thermogenesis. This hormone elevates the basal body temperature by increasing cellular mitochondrial density and uncoupling in order to promote beetle survival. We demonstrate that this hormone activates UCP4- mediated uncoupled respiration through adipokinetic hormone receptor (AKHR). This signal serves as a novel fat-burning activator that utilizes a conserved mechanism to promote thermogenesis not only in beetles, nematode and flies, but also in mice, protecting the mice against cold and tumor growth. This hormone represents a new strategy to manipulate fat thermogenesis.
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Affiliation(s)
- Lilin Zhao
- Institute of Zoology, Chinese Academy of Sciences
| | - Jiao Zhou
- Institute of Zoology, Chinese Academy of Sciences
| | - Junxian Chen
- Institute of Zoology, Chinese Academy of Sciences
| | | | | | | | - Defeng Li
- Institute of Microbiology, Chinese Academy of Sciences
| | - Jing Ning
- Institute of Zoology, Chinese Academy of Sciences
| | - Xinchen Wang
- Institute of Zoology, Chinese Academy of Sciences
| | - Wanzhu Jin
- Institute of Zoology, Chinese Academy of Sciences
| | - Kevin Mai
- Department of Chemistry, University of Florida
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Huynh K, Smith BR, Macdonald SJ, Long AD. Genetic variation in chromatin state across multiple tissues in Drosophila melanogaster. PLoS Genet 2023; 19:e1010439. [PMID: 37146087 PMCID: PMC10191298 DOI: 10.1371/journal.pgen.1010439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 05/17/2023] [Accepted: 04/20/2023] [Indexed: 05/07/2023] Open
Abstract
We use ATAC-seq to examine chromatin accessibility for four different tissues in Drosophila melanogaster: adult female brain, ovaries, and both wing and eye-antennal imaginal discs from males. Each tissue is assayed in eight different inbred strain genetic backgrounds, seven associated with a reference quality genome assembly. We develop a method for the quantile normalization of ATAC-seq fragments and test for differences in coverage among genotypes, tissues, and their interaction at 44099 peaks throughout the euchromatic genome. For the strains with reference quality genome assemblies, we correct ATAC-seq profiles for read mis-mapping due to nearby polymorphic structural variants (SVs). Comparing coverage among genotypes without accounting for SVs results in a highly elevated rate (55%) of identifying false positive differences in chromatin state between genotypes. After SV correction, we identify 1050, 30383, and 4508 regions whose peak heights are polymorphic among genotypes, among tissues, or exhibit genotype-by-tissue interactions, respectively. Finally, we identify 3988 candidate causative variants that explain at least 80% of the variance in chromatin state at nearby ATAC-seq peaks.
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Affiliation(s)
- Khoi Huynh
- Department of Ecology and Evolutionary Biology, University of California, Irvine, California, United States of America
| | - Brittny R. Smith
- Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, United States of America
| | - Stuart J. Macdonald
- Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, United States of America
- Center for Computational Biology, University of Kansas, Lawrence, Kansas, United States of America
| | - Anthony D. Long
- Department of Ecology and Evolutionary Biology, University of California, Irvine, California, United States of America
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22
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Pandey P, Wall PK, Lopez SR, Dubuisson OS, Zunica ERM, Dantas WS, Kirwan JP, Axelrod CL, Johnson AE. A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.04.25.538137. [PMID: 37163058 PMCID: PMC10168263 DOI: 10.1101/2023.04.25.538137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the dec2 gene ( dec2 P384R ) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2 P384R mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep. To test this directly, we used a Drosophila model to study the effects of the dec2 P384R mutation on animal health. Expression of human dec2 P384R in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, dec2 P384R mutants lived significantly longer with improved health despite sleeping less. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that upregulation of pro-health pathways also contributes to the short sleep phenotype, and this phenomenon may extend to other pro-longevity models.
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23
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Oxenkrug G, Navrotska V. Extension of life span by down-regulation of enzymes catalyzing tryptophan conversion into kynurenine: Possible implications for mechanisms of aging. Exp Biol Med (Maywood) 2023; 248:573-577. [PMID: 37300401 PMCID: PMC10350802 DOI: 10.1177/15353702231179411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023] Open
Abstract
The end products of catabolism of tryptophan (Trp), an essential amino acid, are known to affect mechanism(s) of aging, a neurodegenerative condition. This review focuses on the possible role of the initial step of Trp catabolism, kynurenine (Kyn) formation from Trp, in aging mechanism(s). Rate-limiting enzymes of Trp conversion into Kyn are tryptophan 2,3-dioxygenase 2 (TDO) or indoleamine 2,3-dioxygenase (IDO). Aging is associated with up-regulated production of cortisol, an activator of TDO, and pro-inflammatory cytokines, inducers of IDO. The other rate-limiting enzyme of Kyn formation from Trp is ATP-binding cassette (ABC) transporter that regulates Trp availability as a substrate for TDO. Inhibitors of TDO (alpha-methyl tryptophan) and ABC transporter (5-methyltryptophan) extended life span of wild-type Drosophila. Life span prolongation was observed in TDO knockdown of Caenorhabditis elegans and in TDO or ABC transporter-deficient Drosophila mutants. Down-regulation of enzymes catalyzing Kyn conversion into kynurenic acid (KYNA) and 3-hydroxykynurenine decreases life span. Considering that down-regulation of Methuselah (MTH) gene prolonged life span, aging-accelerating effect of KYNA, a GPR35/MTH agonist, might depend on MTH gene activation. Mice treated with TDO inhibitor, benserazide, an ingredient of anti-Parkinson medication carbidopa, and TDO-deficient Drosophila mutants were resistant to inducement of aging-associated Metabolic Syndrome by high-sugar or high-fat diets. Up-regulation of Kyn formation was associated with accelerated aging and increased mortality in human subjects. Trp-Kyn pathway is evolutionary conserved (from yeasts, through insects, worms, vertebrates to humans). Further studies might explore possible antiaging effect of down-regulation of Kyn formation from Trp by dietary, pharmacological, and genetic interventions.
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24
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Hanson MA, Lemaitre B. Antimicrobial peptides do not directly contribute to aging in Drosophila, but improve lifespan by preventing dysbiosis. Dis Model Mech 2023; 16:dmm049965. [PMID: 36847474 PMCID: PMC10163324 DOI: 10.1242/dmm.049965] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 02/20/2023] [Indexed: 03/01/2023] Open
Abstract
Antimicrobial peptides (AMPs) are innate immune effectors first studied for their role in host defence. Recent studies have implicated these peptides in the clearance of aberrant cells and in neurodegenerative syndromes. In Drosophila, many AMPs are produced downstream of Toll and Imd NF-κB pathways upon infection. Upon aging, AMPs are upregulated, drawing attention to these molecules as possible causes of age-associated inflammatory diseases. However, functional studies overexpressing or silencing these genes have been inconclusive. Using an isogenic set of AMP gene deletions, we investigated the net impact of AMPs on aging. Overall, we found no major effect of individual AMPs on lifespan, with the possible exception of Defensin. However, ΔAMP14 flies lacking seven AMP gene families displayed reduced lifespan. Increased bacterial load in the food of aged ΔAMP14 flies suggested that their lifespan reduction was due to microbiome dysbiosis, consistent with a previous study. Moreover, germ-free conditions extended the lifespan of ΔAMP14 flies. Overall, our results did not point to an overt role of individual AMPs in lifespan. Instead, we found that AMPs collectively impact lifespan by preventing dysbiosis during aging.
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Affiliation(s)
- Mark A. Hanson
- Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
| | - Bruno Lemaitre
- Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
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25
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Limbania D, Turner GL, Wasserman SM. Dehydrated Drosophila melanogaster track a water plume in tethered flight. iScience 2023; 26:106266. [PMID: 36915685 PMCID: PMC10005904 DOI: 10.1016/j.isci.2023.106266] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/09/2022] [Accepted: 02/17/2023] [Indexed: 03/11/2023] Open
Abstract
Perception of sensory stimuli can be modulated by changes in internal state to drive contextually appropriate behavior. For example, dehydration is a threat to terrestrial animals, especially to Drosophila melanogaster due to their large surface area to volume ratio, particularly under the energy demands of flight. While hydrated D. melanogaster avoid water cues, while walking, dehydration leads to water-seeking behavior. We show that in tethered flight, hydrated flies ignore a water stimulus, whereas dehydrated flies track a water plume. Antennal occlusions eliminate odor and water plume tracking, whereas inactivation of moist sensing neurons in the antennae disrupts water tracking only upon starvation and dehydration. Elimination of the olfactory coreceptor eradicates odor tracking while leaving water-seeking behavior intact in dehydrated flies. Our results suggest that while similar hygrosensory receptors may be used for walking and in-flight hygrotaxis, the temporal dynamics of modulating the perception of water vary with behavioral state.
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Affiliation(s)
- Daniela Limbania
- Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Grace Lynn Turner
- Department of Neuroscience, Wellesley College, Wellesley, MA 02481, USA
| | - Sara M Wasserman
- Department of Neuroscience, Wellesley College, Wellesley, MA 02481, USA
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26
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Lucas ER, Nagi SC, Egyir-Yawson A, Essandoh J, Dadzie S, Chabi J, Djogbénou LS, Medjigbodo AA, Edi CV, Ketoh GK, Koudou BG, Van't Hof AE, Rippon EJ, Pipini D, Harding NJ, Dyer NA, Cerdeira LT, Clarkson CS, Kwiatkowski DP, Miles A, Donnelly MJ, Weetman D. Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae s.l. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.13.523889. [PMID: 36712022 PMCID: PMC9882144 DOI: 10.1101/2023.01.13.523889] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of the most widespread tools currently used to control malaria. The genetic underpinnings of resistance are still only partially understood, with much of the variance in resistance phenotype left unexplained. We performed a multi-country large scale genome-wide association study of resistance to two insecticides widely used in malaria control: deltamethrin and pirimiphos-methyl. Using a bioassay methodology designed to maximise the phenotypic difference between resistant and susceptible samples, we sequenced 969 phenotyped female An. gambiae and An. coluzzii from ten locations across four countries in West Africa (Benin, Côte d'Ivoire, Ghana and Togo), identifying single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) segregating in the populations. The patterns of resistance association were highly multiallelic and variable between populations, with different genomic regions contributing to resistance, as well as different mutations within a given region. While the strongest and most consistent association with deltamethrin resistance came from the region around Cyp6aa1 , this resistance was based on a combination of several independent CNVs in An. coluzzii , and on a non-CNV bearing haplotype in An. gambiae . Further signals involved a range of cytochrome P450, mitochondrial, and immunity genes. Similarly, for pirimiphos-methyl, while the strongest signal came from the region of Ace1 , more widespread signals included cytochrome P450s, glutathione S-transferases, and a subunit of the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes were associated with resistance to both insecticide classes, suggesting possible cross-resistance mechanisms. These locally-varying, multigenic and multiallelic patterns highlight the challenges involved in genomic monitoring and surveillance of resistance, and form the basis for improvement of methods used to detect and predict resistance. Based on simulations of resistance variants, we recommend that yet larger scale studies, exceeding 500 phenotyped samples per population, are required to better identify associated genomic regions.
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Affiliation(s)
- Eric R Lucas
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
| | - Sanjay C Nagi
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
| | | | - John Essandoh
- Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Sam Dadzie
- Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Joseph Chabi
- Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Luc S Djogbénou
- Tropical Infectious Diseases Research Centre (TIDRC), Université d'Abomey-Calavi (UAC), 01 B.P. 526, Cotonou, Benin
| | - Adandé A Medjigbodo
- Tropical Infectious Diseases Research Centre (TIDRC), Université d'Abomey-Calavi (UAC), 01 B.P. 526, Cotonou, Benin
| | - Constant V Edi
- Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, 01 BP 1303 Abidjan 01, Côte d'Ivoire
| | - Guillaume K Ketoh
- Laboratory of Ecology and Ecotoxicology, Department of Zoology, Faculty of Sciences, Université de Lomé, 01 B.P: 1515 Lomé 01, Togo
| | - Benjamin G Koudou
- Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, 01 BP 1303 Abidjan 01, Côte d'Ivoire
| | - Arjen E Van't Hof
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
- Biology Centre of the Czech Academy of Sciences, Institute of Entomology, Branišovská 31, 370 05 České Budějovice, Czech Republic
| | - Emily J Rippon
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
| | - Dimitra Pipini
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
| | - Nicholas J Harding
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
| | - Naomi A Dyer
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
| | - Louise T Cerdeira
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
| | - Chris S Clarkson
- Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
| | | | - Alistair Miles
- Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
| | - Martin J Donnelly
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
- Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
| | - David Weetman
- Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
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27
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Yoon JS, Ahn SJ, Choi MY. Selection and Comparative Gene Expression of Midgut-Specific Targets for Drosophila suzukii. INSECTS 2023; 14:76. [PMID: 36662004 PMCID: PMC9864236 DOI: 10.3390/insects14010076] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/03/2023] [Accepted: 01/08/2023] [Indexed: 06/17/2023]
Abstract
Spotted-wing drosophila (SWD), Drosophila suzukii, is a destructive and invasive pest that attacks most small fruits and cherries. The current management for SWD involves the use of conventional insecticides. In an effort to develop a biologically based control option, the application of RNA interference (RNAi) has been investigated. To develop an RNAi approach, suitable targets must be identified, and an efficient delivery method must be developed for introducing the double-stranded RNA (dsRNA) in the midgut. In D. suzukii, we previously found that dsRNA nucleases actively degrade dsRNA molecules in the midgut. In this study, we focused on identifying biological targets focused on the midgut membrane. The profile of midgut-specific genes was analyzed and compared with the genes expressed in the whole-body using transcriptome analysis. Differential gene expression analysis revealed that 1921 contigs were upregulated and 1834 contigs were downregulated in the midgut when compared to genes from other body tissues. We chose ten midgut-specifically upregulated genes and empirically confirmed their expressions. We are particularly interested in the midgut membrane proteins, including G protein-coupled receptors (GPCRs) such as diuretic hormone 31 (DH31) receptor, neuropeptide F (NPF) recepror, toll-9, adhesion receptors, methuselah (mth), and gustatory receptor, because insect GPCRs have been offered great potential for next-generation pest management.
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Affiliation(s)
- June-Sun Yoon
- USDA Agricultural Research Service, Horticultural Crops Research Unit, Corvallis, OR 97331, USA
- Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju 54596, Republic of Korea
| | - Seung-Joon Ahn
- Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA
| | - Man-Yeon Choi
- USDA Agricultural Research Service, Horticultural Crops Research Unit, Corvallis, OR 97331, USA
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28
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Aggarwal DD, Mishra P, Singh M. An analysis of direct and indirect effects in Drosophila melanogaster undergoing a few cycles of experimental evolution for stress-related traits. Comp Biochem Physiol B Biochem Mol Biol 2023; 263:110795. [PMID: 35970341 DOI: 10.1016/j.cbpb.2022.110795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 08/04/2022] [Accepted: 08/08/2022] [Indexed: 10/15/2022]
Abstract
The physiological mechanisms underpinning adaptations to starvation and cold stresses have been extensively studied in Drosophila, yet the understanding of correlated changes in stress-related and life-history traits, as well as the energetics of stress tolerance, still remains elusive. To answer the questions empirically in this context, we allowed D. melanogaster to evolve for either increased starvation or cold tolerance (24-generations / regime) in an experimental evolution system, and examined whether selection of either trait affects un-selected stress trait, as well as the impacts potential changes in life-history and mating success-related traits. Our results revealed remarkable changes in starvation/cold tolerance (up to 1.5-fold) as a direct effect of selection, while cold tolerance had been dramatically reduced (1.26-fold) in the starvation tolerant (ST) lines compared to control counterparts, although no such changes were evident in cold-tolerant (CT) lines. ST lines exhibited a higher level of body lipids and a reduced level of trehalose content, while CT lines accumulated a greater levels of body lipid and trehalose contents. Noticeably, we found that selection for starvation or cold tolerance positively correlates with larval development time, longevity, and copulation duration, indicating that these traits are among the most common targets of selection trajectories shaping stress tolerance. Altogether, this study highlights the complexity of mechanisms evolved in ST lines that contribute to enhanced starvation tolerance, but also negatively impact cold tolerance. Nevertheless, mechanisms foraging enhanced cold tolerance in CT lines appear not to target starvation tolerance. Moreover, the parallel changes in life history/mating success traits across stress regimes could indicate some generic pathways evolved in stressful environments, targeting life-history and mating success characteristics to optimize fitness.
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Affiliation(s)
- Dau Dayal Aggarwal
- Department of Biochemistry, University of Delhi South Campus, New Delhi 110021, India.
| | - Prachi Mishra
- Department of Biochemistry, University of Delhi South Campus, New Delhi 110021, India
| | - Manvender Singh
- Department of Biotechnology, University Institute of Technology, Maharshi Dayanand University, Rohtak 124001, India
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29
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Techa S, Thongda W, Bunphimpapha P, Ittarat W, Boonbangyang M, Wilantho A, Ngamphiw C, Pratoomchat B, Nounurai P, Piyapattanakorn S. Isolation and functional identification of secretin family G-protein coupled receptor from Y-organ of the mud crab, Scylla olivacea. Gene X 2023; 848:146900. [DOI: 10.1016/j.gene.2022.146900] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 09/09/2022] [Accepted: 09/13/2022] [Indexed: 12/31/2022] Open
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30
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Kubinyi E. Biologia Futura: four questions about ageing and the future of relevant animal models. Biol Futur 2022; 73:385-391. [PMID: 36131217 DOI: 10.1007/s42977-022-00135-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 09/02/2022] [Indexed: 01/10/2023]
Abstract
Understanding how active and healthy ageing can be achieved is one of the most relevant global problems. In this review, I use the "Four questions" framework of Tinbergen to investigate how ageing works, how it might contribute to the survival of species, how it develops during the lifetime of (human) individuals and how it evolved. The focus of ageing research is usually on losses, although trajectories in later life show heterogeneity and many individuals experience healthy ageing. In humans, mild changes in cognition might be a typical part of ageing, but deficits are a sign of pathology. The ageing of the world's populations, and relatedly, the growing number of pathologically ageing people, is one of the major global problems. Animal models can help to understand the intrinsic and extrinsic factors contributing to ageing.
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Affiliation(s)
- Enikő Kubinyi
- Department of Ethology, ELTE Eötvös Loránd University, Budapest, Hungary. .,MTA-ELTE Lendület "Momentum" Companion Animal Research Group, Budapest, Hungary.
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31
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Chen Y, Wang Q, Luo H, Deng S, Tian Y, Wang S. Mechanisms of the ethanol extract of Gelidium amansii for slow aging in high-fat male Drosophila by metabolomic analysis. Food Funct 2022; 13:10110-10120. [PMID: 36102920 DOI: 10.1039/d2fo02116a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Gelidium amansii (GA) is a kind of red alga homologous to medicine and food and is distributed all over the world. Studies on GA are mainly focused on its polysaccharides, with little research on the ethanol extract. The ethanol extract of Gelidium amansii (GAE) was subjected to a reverse-phase column to obtain 7 components. Among them, 100% methanol solution (GAM), enriched with phytene-1,2-diol, exhibited the strongest DPPH free radical scavenging activity (IC50 = 0.17 mg mL-1). Subsequently, high-fat male flies (HMFs) were used as a model to explore the antioxidant and anti-aging effects of GAM in vivo. Studies showed that GAM can effectively prolong the lifespan of HMFs. When GAM concentrations were 0.2 and 1.0 mg mL-1, the average lifespan of HMFs was increased by 28.7 and 40.7%, respectively, while the longest lifespan of HMFs was increased by 20.55% and 32.88%, respectively. Further research revealed that GAM can significantly downregulate the levels of malondialdehyde (MDA) and protein carbonyl (PCO), and can significantly upregulate the levels of catalase (CAT) and total superoxide dismutase (T-SOD). In addition, by analyzing differential metabolites, we found that GAM relieves aging caused by oxidative stress by regulating amino acid, lipid, sugar, and energy metabolism. The GAM group significantly regulated the levels of adenine, cholic acid, glutamate, L-proline, niacin, and stachyose which tend to recover to the levels of the normal diet male fly (NMF) group. In general, our research provides ideas for the high-value utilization of GA and provides a lead compound for the research and development of anti-aging food or medicine.
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Affiliation(s)
- Yushi Chen
- College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China.
| | - Qishen Wang
- College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China.
| | - Haitao Luo
- College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China.
| | - Shanggui Deng
- College of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, China
| | - Yongqi Tian
- College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China.
| | - Shaoyun Wang
- College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China.
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32
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Brooks D, Bawa S, Bontrager A, Stetsiv M, Guo Y, Geisbrecht ER. Independent pathways control muscle tissue size and sarcomere remodeling. Dev Biol 2022; 490:1-12. [PMID: 35760368 PMCID: PMC9648737 DOI: 10.1016/j.ydbio.2022.06.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 06/03/2022] [Accepted: 06/21/2022] [Indexed: 01/09/2023]
Abstract
Cell growth and proliferation must be balanced during development to attain a final adult size with the appropriate proportions of internal organs to maximize fitness and reproduction. While multiple signaling pathways coordinate Drosophila development, it is unclear how multi-organ communication within and between tissues converge to regulate systemic growth. One such growth pathway, mediated by insulin-like peptides that bind to and activate the insulin receptor in multiple target tissues, is a primary mediator of organismal size. Here we uncover a signaling role for the NUAK serine/threonine kinase in muscle tissue that impinges upon insulin pathway activity to limit overall body size, including a reduction in the growth of individual organs. In skeletal muscle tissue, manipulation of NUAK or insulin pathway components influences sarcomere number concomitant with modulation of thin and thick filament lengths, possibly by modulating the localization of Lasp, a nebulin repeat protein known to set thin filament length. This mode of sarcomere remodeling does not occur in other mutants that also exhibit smaller muscles, suggesting that a sensing mechanism exists in muscle tissue to regulate sarcomere growth that is independent of tissue size control.
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Affiliation(s)
- David Brooks
- Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA
| | - Simranjot Bawa
- Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA
| | - Alexandria Bontrager
- Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA
| | - Marta Stetsiv
- Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA
| | - Yungui Guo
- Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA
| | - Erika R Geisbrecht
- Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA.
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33
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Brenner C. Sirtuins are Not Conserved Longevity Genes. LIFE METABOLISM 2022; 1:122-133. [PMID: 37035412 PMCID: PMC10081735 DOI: 10.1093/lifemeta/loac025] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/11/2022] [Accepted: 09/20/2022] [Indexed: 11/14/2022]
Abstract
It is central to biology that sequence conservation suggests functional conservation. Animal longevity is an emergent property of selected traits that integrates capacities to perform physical and mental functions after reproductive maturity. Though the yeast SIR2 gene was nominated as a longevity gene based on extended replicative longevity of old mother cells, this is not a selected trait: SIR2 is selected against in chronological aging and the direct targets of SIR2 in replicative lifespan are not conserved. Though it would be difficult to imagine how a gene that advantages 1 in 5 million yeast cells could have anticipated causes of aging in animals, overexpression of SIR2 homologs was tested in invertebrates for longevity. Because artifactual positive results were reported years before they were sorted out and because it was not known that SIR2 functions as a pro-aging gene in yeast chronological aging and in flies subject to amino acid deprivation, a global pursuit of longevity phenotypes was driven by a mixture of framing bias, confirmation bias and hype. Review articles that propagate these biases are so rampant that few investigators have considered how weak the case ever was for sirtuins as longevity genes. Acknowledging that a few positive associations between sirtuins and longevity have been identified after thousands of person-years and billions of dollars of effort, we review the data and suggest rejection of the notions that sirtuins 1) have any specific connection to lifespan in animals and 2) are primary mediators of the beneficial effects of NAD repletion.
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Affiliation(s)
- Charles Brenner
- Department of Diabetes & Cancer Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010USA
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Fu N, Li J, Ren L, Li X, Wang M, Li F, Zong S, Luo Y. Chromosome-level genome assembly of Monochamus saltuarius reveals its adaptation and interaction mechanism with pine wood nematode. Int J Biol Macromol 2022; 222:325-336. [PMID: 36115455 DOI: 10.1016/j.ijbiomac.2022.09.108] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 08/22/2022] [Accepted: 09/10/2022] [Indexed: 11/05/2022]
Abstract
Monochamus saltuarius (Coleoptera: Cerambycidae) was reported as the vector beetle of the pine wood nematode (PWN, Bursaphelenchus xylophilus) in Japan and Europe. It was first reported to transmitted the PWN to native Pinus species in 2018 in Liaoning Province, China. However, the lack of genomic resources has limited the in-depth understanding of its interspecific relationship with PWN. Here, we obtained a chromosome-level reference genome of M. saltuarius combining Illumina, Nanopore and Hi-C sequencing technologies. We assembled the scaffolds into ten chromosomes (including an X chromosome) and obtained a 682.23 Mb chromosome-level genome with a N50 of 73.69 Mb. In total, 427.67 Mb (62.69 %) repeat sequences were identified and 14, 492 protein-coding genes were predicted, of which 93.06 % were annotated. We described the mth/mthl, P450, OBP and OR gene families associated with the vector beetle's development and resistance, as well as the host selection and adaptation, which serve as a valuable resource for understanding the host adaptation in insects during evolution. This high quality reference genome of M. saltuarius also provide new avenues for researching the mechanism of this synergistic damage between vector beetles and PWN.
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Affiliation(s)
- Ningning Fu
- Beijing Key Laboratory for Forest Pest Control, Beijing Forestry University, Beijing 100083, China
| | - Jiaxing Li
- Beijing Key Laboratory for Forest Pest Control, Beijing Forestry University, Beijing 100083, China
| | - Lili Ren
- Beijing Key Laboratory for Forest Pest Control, Beijing Forestry University, Beijing 100083, China.
| | | | - Ming Wang
- Beijing Key Laboratory for Forest Pest Control, Beijing Forestry University, Beijing 100083, China
| | - Fengqi Li
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, Guizhou 550025, China
| | - Shixiang Zong
- Beijing Key Laboratory for Forest Pest Control, Beijing Forestry University, Beijing 100083, China
| | - Youqing Luo
- Beijing Key Laboratory for Forest Pest Control, Beijing Forestry University, Beijing 100083, China.
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35
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Beneficial commensal bacteria promote Drosophila growth by down-regulating the expression of peptidoglycan recognition proteins. iScience 2022; 25:104357. [PMID: 35601912 PMCID: PMC9121327 DOI: 10.1016/j.isci.2022.104357] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 11/24/2021] [Accepted: 04/29/2022] [Indexed: 11/22/2022] Open
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Paten AM, Colin T, Coppin CW, Court LN, Barron AB, Oakeshott JG, Morgan MJ. Non-additive gene interactions underpin molecular and phenotypic responses in honey bee larvae exposed to imidacloprid and thymol. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 814:152614. [PMID: 34963587 DOI: 10.1016/j.scitotenv.2021.152614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/17/2021] [Accepted: 12/18/2021] [Indexed: 06/14/2023]
Abstract
Understanding the cumulative risk of chemical mixtures at environmentally realistic concentrations is a key challenge in honey bee ecotoxicology. Ecotoxicogenomics, including transcriptomics, measures responses in individual organisms at the molecular level which can provide insights into the mechanisms underlying phenotypic responses induced by one or more stressors and link impacts on individuals to populations. Here, fifth instar honey bee larvae were sampled from a previously reported field experiment exploring the phenotypic impacts of environmentally realistic chronic exposures of the pesticide imidacloprid (5 μg.kg-1 for six weeks) and the acaricide thymol (250 g.kg-1 applied via Apiguard gel in-hive for four weeks), both separately and in combination. RNA-seq was used to discover individual and interactive chemical effects on larval gene expression and to uncover molecular mechanisms linked to reported adult and colony phenotypes. The separate and combined treatments had distinct gene expression profiles which represented differentially affected signaling and metabolic pathways. The molecular signature of the mixture was characterised by additive interactions in canonical stress responses associated with oxidative stress and detoxification, and non-additive interactions in secondary responses including developmental, neurological, and immune pathways. Novel emergent impacts on eye development genes correlated with long-term defects in visual learning performance as adults. This is consistent with these chemicals working through independent modes of action that combine to impact common downstream pathways, and highlights the importance of establishing mechanistic links between molecular and phenotypic responses when predicting effects of chemical mixtures on ecologically relevant population outcomes.
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Affiliation(s)
- Amy M Paten
- Land and Water, CSIRO, Black Mountain, Canberra, ACT 2601, Australia.
| | - Théotime Colin
- Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Chris W Coppin
- Land and Water, CSIRO, Black Mountain, Canberra, ACT 2601, Australia.
| | - Leon N Court
- Land and Water, CSIRO, Black Mountain, Canberra, ACT 2601, Australia.
| | - Andrew B Barron
- Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
| | - John G Oakeshott
- Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia; Applied Biosciences, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Matthew J Morgan
- Land and Water, CSIRO, Black Mountain, Canberra, ACT 2601, Australia.
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Hutfilz C. Endocrine Regulation of Lifespan in Insect Diapause. Front Physiol 2022; 13:825057. [PMID: 35242054 PMCID: PMC8886022 DOI: 10.3389/fphys.2022.825057] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/25/2022] [Indexed: 01/27/2023] Open
Abstract
Diapause is a physiological adaptation to conditions that are unfavorable for growth or reproduction. During diapause, animals become long-lived, stress-resistant, developmentally static, and non-reproductive, in the case of diapausing adults. Diapause has been observed at all developmental stages in both vertebrates and invertebrates. In adults, diapause traits weaken into adaptations such as hibernation, estivation, dormancy, or torpor, which represent evolutionarily diverse versions of the traditional diapause traits. These traits are regulated through modifications of the endocrine program guiding development. In insects, this typically includes changes in molting hormones, as well as metabolic signals that limit growth while skewing the organism's energetic demands toward conservation. While much work has been done to characterize these modifications, the interactions between hormones and their downstream consequences are incompletely understood. The current state of diapause endocrinology is reviewed here to highlight the relevance of diapause beyond its use as a model to study seasonality and development. Specifically, insect diapause is an emerging model to study mechanisms that determine lifespan. The induction of diapause represents a dramatic change in the normal progression of age. Hormones such as juvenile hormone, 20-hydroxyecdysone, and prothoracicotropic hormone are well-known to modulate this plasticity. The induction of diapause-and by extension, the cessation of normal aging-is coordinated by interactions between these pathways. However, research directly connecting diapause endocrinology to the biology of aging is lacking. This review explores connections between diapause and aging through the perspective of endocrine signaling. The current state of research in both fields suggests appreciable overlap that will greatly contribute to our understanding of diapause and lifespan determination.
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Zhang YJ, Jiang L, Ahamd S, Chen Y, Zhang JY, Stanley D, Miao H, Ge LQ. The octopamine receptor, OA2B2, modulates stress resistance and reproduction in Nilaparvata lugens Stål (Hemiptera: Delphacidae). INSECT MOLECULAR BIOLOGY 2022; 31:33-48. [PMID: 34480382 DOI: 10.1111/imb.12736] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 08/19/2021] [Accepted: 08/31/2021] [Indexed: 06/13/2023]
Abstract
The brown planthopper (BPH), Nilaparvata lugens (Stål) is a resurgent pest of rice crops throughout Asia. We recently discovered that octopamine (OA) and OA2B2 operate in the BPH mating system, where it mediates a wide range of molecular, physiological and behavioural changes. Here, we report on outcomes of experiments designed to test the hypothesis that OA/OA2B2 signalling mediates responses to three abiotic stressors, starvation, high temperature (37 °C), and induced oxidative stress. We found per os RNAi-mediated OA2B2 silencing led to significantly decreased survival, measured in days, following exposure to each of these stressors. We selected a biologically costly process, reproductive biology, as a biotic stressor. Silencing of OA2B2 led to decreased total protein content in ovaries and fat bodies, downregulated expression of vitellogenin (Vg) and Vg receptor (VgR), inhibited fat body Vg protein synthesis, shortened the oviposition period, prolonged the preoviposition period, reduced the number of laid eggs, body weight and female longevity. In addition, the silencing treatments also led to inhibited ovarian development, and ovarian Vg uptake, reduced numbers of egg masses and offspring and lower hatching rates and population growth index. These data support our hypothesis that OA2B2 acts in mediating BPH resistance to biotic and abiotic stressors.
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Affiliation(s)
- Y J Zhang
- School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, Jiangsu Province, China
- College of Mechanical Engineering, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - L Jiang
- School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - S Ahamd
- School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Y Chen
- School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - J Y Zhang
- School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - D Stanley
- USDA/Agricultural Research Service, Biological Control of Insects Research Laboratory, Columbia, MO, USA
| | - H Miao
- College of Mechanical Engineering, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - L Q Ge
- School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, Jiangsu Province, China
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Liu Y, Liu Q, Chen D, Matsuura A, Xiang L, Qi J. Inokosterone from Gentiana rigescens Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction. Antioxidants (Basel) 2022; 11:antiox11020214. [PMID: 35204097 PMCID: PMC8868264 DOI: 10.3390/antiox11020214] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 02/04/2023] Open
Abstract
In the present study, replicative lifespan and chronological lifespan assays of yeast were used to double-screen antiaging compounds from Gentiana rigescens Franch, a Chinese herb medicine. Inokosterone from G. rigescens Franch extended not only the replicative lifespan of K6001 yeast but also the chronological lifespan of YOM36 yeast. Furthermore, it can enhance the survival ability of mammalian cells. In order to understand the mechanism of action of this compound, this study focused on antioxidative stress and autophagy when performing the analysis. The increased cell survival rate under oxidative stress conditions, antioxidant enzyme activity and gene expression were observed in the inokosterone-treated groups. Meanwhile, the reactive oxygen species (ROS) and lipid peroxidation of yeast were obviously decreased. Additionally, the macroautophagy and mitophagy in YOM38-GFP-ATG8 yeast were increased upon inokosterone treatment, respectively. At the same time, the cleavage-free GFP from GFP-ATG8 in the cytoplasm and the ubiquitin of the mitochondria at the protein level were markedly enhanced after incubation with inokosterone. Furthermore, we investigated the effect of inokosterone on antioxidative stress and autophagy in mammalian cells, and the relationship between ROS and autophagy. The ROS, malondialdehyde (MDA) were significantly decreased, and the autophagosomes in mammalian cells were obviously increased after inokosterone treatment. The autophagosomes in ∆sod1 yeast with a K6001 background had no obvious changes, and the ROS and MDA of ∆sod1 yeast were increased compared with K6001 yeast. The increase of autophagosomes and the reduction of ROS and MDA in ∆sod1 yeast were observed after treatment with inokosterone. Meanwhile, the reduction of the ROS level and the increase of the SOD1 gene expression of K6001 yeast lacking autophagy were observed after treatment with inokosterone. In order to indicate whether the genes related to antioxidant enzymes and autophagy were involved in the antiaging effect of inokosterone, mutants of K6001 yeast were constructed to conduct a lifespan assay. The replicative lifespans of ∆sod1, ∆sod2, ∆uth1, ∆skn7, ∆gpx, ∆cat, ∆atg2, and ∆atg32 of K6001 yeast were not affected by inokosterone. These results suggest that inokosterone exerted an antiaging activity via antioxidative stress and increased autophagy activation; autophagy affected the ROS levels of yeast via the regulation of SOD1 gene expression.
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Affiliation(s)
- Yanan Liu
- College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China; (Y.L.); (Q.L.); (D.C.)
| | - Qian Liu
- College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China; (Y.L.); (Q.L.); (D.C.)
| | - Danni Chen
- College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China; (Y.L.); (Q.L.); (D.C.)
| | - Akira Matsuura
- Department of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, Japan;
| | - Lan Xiang
- College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China; (Y.L.); (Q.L.); (D.C.)
- Correspondence: (L.X.); (J.Q.); Tel.: +86-0571-8820-8627 (J.Q.)
| | - Jianhua Qi
- College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China; (Y.L.); (Q.L.); (D.C.)
- Correspondence: (L.X.); (J.Q.); Tel.: +86-0571-8820-8627 (J.Q.)
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40
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Promislow DEL, Flatt T, Bonduriansky R. The Biology of Aging in Insects: From Drosophila to Other Insects and Back. ANNUAL REVIEW OF ENTOMOLOGY 2022; 67:83-103. [PMID: 34590891 PMCID: PMC8940561 DOI: 10.1146/annurev-ento-061621-064341] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
An enormous amount of work has been done on aging in Drosophila melanogaster, a classical genetic and molecular model system, but also in numerous other insects. However, these two extensive bodies of work remain poorly integrated to date. Studies in Drosophila often explore genetic, developmental, physiological, and nutrition-related aspects of aging in the lab, while studies in other insects often explore ecological, social, and somatic aspects of aging in both lab and natural populations. Alongside exciting genomic and molecular research advances in aging in Drosophila, many new studies have also been published on aging in various other insects, including studies on aging in natural populations of diverse species. However, no broad synthesis of these largely separate bodies of work has been attempted. In this review, we endeavor to synthesize these two semi-independent literatures to facilitate collaboration and foster the exchange of ideas and research tools. While lab studies of Drosophila have illuminated many fundamental aspects of senescence, the stunning diversity of aging patterns among insects, especially in the context of their rich ecology, remains vastlyunderstudied. Coupled with field studies and novel, more easily applicable molecular methods, this represents a major opportunity for deepening our understanding of the biology of aging in insects and beyond.
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Affiliation(s)
- Daniel E L Promislow
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA;
- Department of Biology, University of Washington, Seattle, Washington 98195, USA
| | - Thomas Flatt
- Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland;
| | - Russell Bonduriansky
- Evolution and Ecology Research Centre, School of Biological, Earth and Environmental Sciences, University of New South Wales Sydney, New South Wales 2052, Australia;
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41
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Lagunas-Rangel FA. G protein-coupled receptors that influence lifespan of human and animal models. Biogerontology 2021; 23:1-19. [PMID: 34860303 PMCID: PMC8888397 DOI: 10.1007/s10522-021-09945-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/22/2021] [Indexed: 12/16/2022]
Abstract
Humanity has always sought to live longer and for this, multiple strategies have been tried with varying results. In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while maintaining good health since they have a substantial participation in a wide variety of processes of human pathophysiology and are one of the main therapeutic targets. In this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the lifespan of animal and human models, and in which we put a special interest in describing the molecular mechanisms involved. Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are those that mimic dietary restriction, those related to insulin signaling and the AMPK and TOR pathways, and those that alter oxidative homeostasis and severe and/or chronic inflammation. We also discuss the possibility of using agonist or antagonist drugs, depending on the beneficial or harmful effects of each GPCR, in order to prolong people's lifespan and healthspan.
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Li YL, Li YX, Wang XP, Kang XL, Guo KQ, Dong DJ, Wang JX, Zhao XF. Identification and Functional Analysis of G Protein-Coupled Receptors in 20-Hydroxyecdysone Signaling From the Helicoverpa armigera Genome. Front Cell Dev Biol 2021; 9:753787. [PMID: 34765604 PMCID: PMC8576438 DOI: 10.3389/fcell.2021.753787] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/30/2021] [Indexed: 11/13/2022] Open
Abstract
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors in animals and humans, which transmit various signals from the extracellular environment into cells. Studies have reported that several GPCRs transmit the same signal; however, the mechanism is unclear. In the present study, we identified all 122 classical GPCRs from the genome of Helicoverpa armigera, a lepidopteran pest species. Twenty-four GPCRs were identified as upregulated at the metamorphic stage by comparing the transcriptomes of the midgut at the metamorphic and feeding stages. Nine of them were confirmed to be upregulated at the metamorphic stage. RNA interference in larvae revealed the prolactin-releasing peptide receptor (PRRPR), smoothened (SMO), adipokinetic hormone receptor (AKHR), and 5-hydroxytryptamine receptor (HTR) are involved in steroid hormone 20-hydroxyecdysone (20E)-promoted pupation. Frizzled 7 (FZD7) is involved in growth, while tachykinin-like peptides receptor 86C (TKR86C) had no effect on growth and pupation. Via these GPCRs, 20E regulated the expression of different genes, respectively, including Pten (encoding phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase), FoxO (encoding forkhead box O), BrZ7 (encoding broad isoform Z7), Kr-h1 (encoding Krüppel homolog 1), Wnt (encoding Wingless/Integrated) and cMyc, with hormone receptor 3 (HHR3) as their common regulating target. PRRPR was identified as a new 20E cell membrane receptor using a binding assay. These data suggested that 20E, via different GPCRs, regulates different gene expression to integrate growth and development.
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Affiliation(s)
- Yan-Li Li
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Yan-Xue Li
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Xiao-Pei Wang
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Xin-Le Kang
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Ke-Qin Guo
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Du-Juan Dong
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Jin-Xing Wang
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Xiao-Fan Zhao
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
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Hayes T, López-Martínez G. Resistance and survival to extreme heat shows circadian and sex-specific patterns in A cavity nesting bee. CURRENT RESEARCH IN INSECT SCIENCE 2021; 1:100020. [PMID: 36003599 PMCID: PMC9387514 DOI: 10.1016/j.cris.2021.100020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 06/14/2023]
Abstract
The pollination services provided by insects have been a crucial part of evolution and survival for many species, including humans. For bees to be efficient pollinators they must survive the environmental insults they face daily. Thus, looking into the short- and long-term effects of heat exposure on bee performance provides us with a foundation for investigating how stress can affect insect pollination. Solitary bees are a great model for investigating the effects of environmental stress on pollinators because the vast majority of insect pollinator species are solitary rather than social. One of the most pervasive environmental stressors to insects is temperature. Here we investigated how a one-hour heat shock affected multiple metrics of performance in the alfalfa leafcutting bee, Megachile rotundata. We found that a short heat shock (1hr at 45°C) can delay adult emergence in males but not females. Bee pupae were rather resilient to a range of high temperature exposures that larvae did not survive. Following heat shock (1hr at 50°C), adult bees were drastically less active than untreated bees, and this reduction in activity was evident over several days. Heat shock also led to a decrease in bee survival and longevity. Additionally, we found a connection between starvation survival after heat shock and time of exposure, where bees exposed in the morning survived longer than those exposed in the afternoon, when they would normally experience heat shock in the field. These data suggest that there is an unexplored daily/circadian component to the stress response in bees likely similar to that seen in flies, nematodes, and plants which is constitutive or preemptive rather than restorative. Taken together our data indicate that single heat shock events have strong potential to negatively impact multiple life history traits correlated with reproduction and fitness.
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Affiliation(s)
- Tayia Hayes
- Department of Natural Sciences and Environmental Health, Mississippi Valley State University, Itta Bena, MS 38941
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44
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The 50th anniversary of the Konopka and Benzer 1971 paper in PNAS: "Clock Mutants of Drosophila melanogaster". Proc Natl Acad Sci U S A 2021; 118:2110171118. [PMID: 34507977 DOI: 10.1073/pnas.2110171118] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2021] [Indexed: 11/18/2022] Open
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45
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Salvadori G, Mirisola MG, Longo VD. Intermittent and Periodic Fasting, Hormones, and Cancer Prevention. Cancers (Basel) 2021; 13:cancers13184587. [PMID: 34572814 PMCID: PMC8472354 DOI: 10.3390/cancers13184587] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 09/09/2021] [Indexed: 12/25/2022] Open
Abstract
The restriction of proteins, amino acids or sugars can have profound effects on the levels of hormones and factors including growth hormone, IGF-1 and insulin. In turn, these can regulate intracellular signaling pathways as well as cellular damage and aging, but also multisystem regeneration. Both intermittent (IF) and periodic fasting (PF) have been shown to have both acute and long-term effects on these hormones. Here, we review the effects of nutrients and fasting on hormones and genes established to affect aging and cancer. We describe the link between dietary interventions and genetic pathways affecting the levels of these hormones and focus on the mechanisms responsible for the cancer preventive effects. We propose that IF and PF can reduce tumor incidence both by delaying aging and preventing DNA damage and immunosenescence and also by killing damaged, pre-cancerous and cancer cells.
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Affiliation(s)
- Giulia Salvadori
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy;
- IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy
| | - Mario Giuseppe Mirisola
- Department of Surgical, Oncological, and Oral Sciences, University of Palermo, 90127 Palermo, Italy;
| | - Valter D. Longo
- IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy
- Department of Biological Sciences, Longevity Institute, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA
- Correspondence:
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Sigrist-Flores SC, Castañeda-Partida L, Campos-Aguilar M, Santos-Cruz LF, Miranda-Gutierrez A, Gallardo-Ortíz IA, Villalobos-Molina R, Dueñas-García IE, Heres-Pulido ME, Piedra-Ibarra E, Rosales-García VH, Jimenez-Flores R, Ponciano-Gómez A. Variation in resistance to oxidative stress in Oregon-(R)R-flare and Canton-S strains of Drosophila melanogaster. Toxicol Res (Camb) 2021; 10:817-823. [PMID: 34484673 DOI: 10.1093/toxres/tfab066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 05/07/2021] [Accepted: 06/25/2021] [Indexed: 11/13/2022] Open
Abstract
All aerobic organisms are susceptible to damage by reactive oxygen species (ROS). ROS-induced damage has been associated with aging and diseases such as metabolic syndrome and cancer. However, not all organisms develop these diseases, nor do they age at the same rate; this is partially due to resistance to oxidative stress, a quantitative trait attributable to the interaction of factors including genetics and environmental. Drosophila melanogaster represents an ideal system to study how genetic variation can affect resistance to oxidative stress. In this work, oxidative stress (total and mitochondrial ROS), antioxidant response, and Cap 'n' collar isoform C and Spineless gene expression, one pesticide resistant (Oregon R(R)-flare) and wild-type (Canton-S) strains of D. melanogaster, were analyzed to test resistance to basal oxidative stress. ROS, catalase, and superoxide dismutase were determined by flow cytometry, and Cap 'n' collar isoform C and Spineless expression by qRT-PCR. The intensity of oxidative stress due to the pro-oxidant zearalenone in both was evaluated by flow cytometry. Data confirm expected differences in oxidative stress between strains that differ in Cyp450s levels. The Oregon (R)R-flare showed greater ROS, total and mitochondrial, compared to Canton-S. Regarding oxidative stress genes expression Cap 'n' collar isoform C and Spineless (Ss), Oregon R(R)-flare strain showed higher expression. In terms of response to zearalenone mycotoxin, Canton-S showed higher ROS concentration. Our data show variation in the resistance to oxidative stress among these strains of D. melanogaster.
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Affiliation(s)
- Santiago Cristobal Sigrist-Flores
- Laboratorio de Inmunología (UMF), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla, C.P. 54090, Estado de México, México
| | - Laura Castañeda-Partida
- Toxicología Genética, Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla C.P. 54090, Estado de México, México
| | - Myriam Campos-Aguilar
- Laboratorio de Inmunología (UMF), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla, C.P. 54090, Estado de México, México
| | - Luis Felipe Santos-Cruz
- Toxicología Genética, Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla C.P. 54090, Estado de México, México
| | - Aranza Miranda-Gutierrez
- Laboratorio de Inmunología (UMF), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla, C.P. 54090, Estado de México, México
| | - I A Gallardo-Ortíz
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla C.P. 54090, Estado de México, México
| | - R Villalobos-Molina
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla C.P. 54090, Estado de México, México
| | - Irma Elena Dueñas-García
- Toxicología Genética, Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla C.P. 54090, Estado de México, México
| | - María Eugenia Heres-Pulido
- Toxicología Genética, Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla C.P. 54090, Estado de México, México
| | - Elías Piedra-Ibarra
- Fisiología Vegetal (UBIPRO), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla C.P. 54090, Estado de México, México
| | - Víctor Hugo Rosales-García
- Laboratorios Nacionales de Servicios Experimentales, Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional. Ciudad de México, La Laguna Ticoman, Gustavo A. Madero, 07340 Mexico City, México
| | - Rafael Jimenez-Flores
- Laboratorio de Inmunología (UMF), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla, C.P. 54090, Estado de México, México
| | - Alberto Ponciano-Gómez
- Laboratorio de Inmunología (UMF), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios N° 1, Los Reyes Iztacala, Tlalnepantla, C.P. 54090, Estado de México, México
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Ji L, Jazwinski SM, Kim S. Frailty and Biological Age. Ann Geriatr Med Res 2021; 25:141-149. [PMID: 34399574 PMCID: PMC8497950 DOI: 10.4235/agmr.21.0080] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 08/10/2021] [Indexed: 12/15/2022] Open
Abstract
A reliable model of biological age is instrumental in the field of geriatrics and gerontology. This model should account for the heterogeneity and plasticity of aging and also accurately predict aging-related adverse outcomes. Epigenetic age models are based on DNA methylation levels at selected genomic sites and can be significant predictors of mortality and healthy/unhealthy aging. However, the biological function of DNA methylation at selected sites is yet to be determined. Frailty is a syndrome resulting from decreased physiological reserves and resilience. The frailty index is a probability-based extension of the concept of frailty. Defined as the proportion of health deficits, the frailty index quantifies the progression of unhealthy aging. The frailty index is currently the best predictor of mortality. It is associated with various biological factors and provides insight into the biological processes of aging. Investigation of the multi-omics factors associated with the frailty index will provide further insight.
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Affiliation(s)
- Lixin Ji
- Tulane University School of Medicine, New Orleans, LA, USA
| | - S Michal Jazwinski
- Tulane Center for Aging & Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Sangkyu Kim
- Tulane Center for Aging & Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
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48
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Developmental ethanol exposure causes central nervous system dysfunction and may slow the aging process in a Drosophila model of fetal alcohol spectrum disorder. Alcohol 2021; 94:65-73. [PMID: 33961967 DOI: 10.1016/j.alcohol.2021.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 03/25/2021] [Accepted: 03/31/2021] [Indexed: 11/21/2022]
Abstract
Alcohol is a known teratogen, and developmental exposure to ethanol results in fetal alcohol spectrum disorder (FASD). Children born with FASD can exhibit a range of symptoms including low birth weight, microcephaly, and neurobehavioral problems. Treatment of patients with FASD is estimated to cost 4 billion dollars per year in the United States alone, and 2 million dollars per affected individual's lifetime. We have established Drosophila melanogaster as a model organism for the study of FASD. Here we report that mutations in Dementin (Dmtn), the Drosophila ortholog of the Alzheimer's disease-associated protein TMCC2, convey sensitivity to developmental ethanol exposure, and provide evidence that Dmtn expression is disrupted by ethanol. In addition, we find that flies reared on ethanol exhibit mild climbing defects suggestive of neurodegeneration. Surprisingly, our data also suggest that flies reared on ethanol age more slowly than control animals, and we find that a number of slow-aging mutants are sensitive to developmental ethanol exposure. Finally, we find that flies reared on ethanol showed a persistent upregulation of genes encoding antioxidant enzymes, which may contribute to a reduced rate of central nervous system aging. Thus, in addition to the well-documented negative effects of developmental alcohol exposure on the nervous system, there may be a previously unsuspected neuroprotective effect in adult animals.
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49
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O'Connor JT, Stevens AC, Shannon EK, Akbar FB, LaFever KS, Narayanan NP, Gailey CD, Hutson MS, Page-McCaw A. Proteolytic activation of Growth-blocking peptides triggers calcium responses through the GPCR Mthl10 during epithelial wound detection. Dev Cell 2021; 56:2160-2175.e5. [PMID: 34273275 DOI: 10.1016/j.devcel.2021.06.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 05/20/2021] [Accepted: 06/25/2021] [Indexed: 12/20/2022]
Abstract
The presence of a wound triggers surrounding cells to initiate repair mechanisms, but it is not clear how cells initially detect wounds. In epithelial cells, the earliest known wound response, occurring within seconds, is a dramatic increase in cytosolic calcium. Here, we show that wounds in the Drosophila notum trigger cytoplasmic calcium increase by activating extracellular cytokines, Growth-blocking peptides (Gbps), which initiate signaling in surrounding epithelial cells through the G-protein-coupled receptor Methuselah-like 10 (Mthl10). Latent Gbps are present in unwounded tissue and are activated by proteolytic cleavage. Using wing discs, we show that multiple protease families can activate Gbps, suggesting that they act as a generalized protease-detector system. We present experimental and computational evidence that proteases released during wound-induced cell damage and lysis serve as the instructive signal: these proteases liberate Gbp ligands, which bind to Mthl10 receptors on surrounding epithelial cells, and activate downstream release of calcium.
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Affiliation(s)
- James T O'Connor
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA; Program in Developmental Biology, Vanderbilt University, Nashville, TN, USA
| | - Aaron C Stevens
- Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, USA
| | - Erica K Shannon
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA; Program in Developmental Biology, Vanderbilt University, Nashville, TN, USA
| | - Fabiha Bushra Akbar
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
| | - Kimberly S LaFever
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
| | - Neil P Narayanan
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
| | - Casey D Gailey
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
| | - M Shane Hutson
- Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, USA; Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA; Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, USA.
| | - Andrea Page-McCaw
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA; Program in Developmental Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
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50
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Liu N, Li T, Wang Y, Liu S. G-Protein Coupled Receptors (GPCRs) in Insects-A Potential Target for New Insecticide Development. Molecules 2021; 26:2993. [PMID: 34069969 PMCID: PMC8157829 DOI: 10.3390/molecules26102993] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 05/10/2021] [Accepted: 05/12/2021] [Indexed: 02/07/2023] Open
Abstract
G-protein coupled receptors (GPCRs) play important roles in cell biology and insects' physiological processes, toxicological response and the development of insecticide resistance. New information on genome sequences, proteomic and transcriptome analysis and expression patterns of GPCRs in organs such as the central nervous system in different organisms has shown the importance of these signaling regulatory GPCRs and their impact on vital cell functions. Our growing understanding of the role played by GPCRs at the cellular, genome, transcriptome and tissue levels is now being utilized to develop new targets that will sidestep many of the problems currently hindering human disease control and insect pest management. This article reviews recent work on the expression and function of GPCRs in insects, focusing on the molecular complexes governing the insect physiology and development of insecticide resistance and examining the genome information for GPCRs in two medically important insects, mosquitoes and house flies, and their orthologs in the model insect species Drosophila melanogaster. The tissue specific distribution and expression of the insect GPCRs is discussed, along with fresh insights into practical aspects of insect physiology and toxicology that could be fundamental for efforts to develop new, more effective, strategies for pest control and resistance management.
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Affiliation(s)
- Nannan Liu
- Department of Entomology and Plant Pathology, Auburn University, Auburn, AL 36849, USA; (T.L.); (Y.W.)
| | - Ting Li
- Department of Entomology and Plant Pathology, Auburn University, Auburn, AL 36849, USA; (T.L.); (Y.W.)
| | - Yifan Wang
- Department of Entomology and Plant Pathology, Auburn University, Auburn, AL 36849, USA; (T.L.); (Y.W.)
| | - Shikai Liu
- College of Fisheries, Ocean University of China, Qingdao 266100, China;
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