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Markus Friedrich, Jeffery W Jones
Affecting lifespan regulation and oxidative stress resistance, the G-protein coupled receptor (GPCR) gene methuselah (mth) plays important roles in the life history of Drosophila melanogaster. Substantial progress has been made in elucidating the molecular pathways by which mth affects these traits, yet conflicting ideas exist as to how old these genetic interactions are as well as how old the mth gene itself is. Root to these issues is the complex gene family history of the Mth/Mthl GPCR family, which experienced independent expansions in a variety of animal clades, leading to at least six subfamilies in insects...
January 11, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Michael Shermer
No abstract text is available yet for this article.
September 20, 2016: Scientific American
Zhengqing Zhang, Huapeng Wang, Chunfeng Hao, Wei Zhang, Miaomiao Yang, Yong Chang, Menglou Li
Dastarcus helophoroides, which has a relatively longer lifespan compared to other insects, is one of the most effective natural enemies of many large-body long-horned beetles. Methuselah (Mth) is associated with the lifespan, stress resistance, and reproduction in Drosophila melanogaster, but Mth is not present in non-drosophiline insects. A number of methuselah-like genes (mth-likes, mthls) have been identified in non-drosophiline insects, but it is still unknown whether they are present in Dastarcus helophoroides...
October 21, 2016: Genes
Renald Delanoue, Eleonora Meschi, Neha Agrawal, Alessandra Mauri, Yonit Tsatskis, Helen McNeill, Pierre Léopold
Animals adapt their growth rate and body size to available nutrients by a general modulation of insulin-insulin-like growth factor signaling. In Drosophila, dietary amino acids promote the release in the hemolymph of brain insulin-like peptides (Dilps), which in turn activate systemic organ growth. Dilp secretion by insulin-producing cells involves a relay through unknown cytokines produced by fat cells. Here, we identify Methuselah (Mth) as a secretin-incretin receptor subfamily member required in the insulin-producing cells for proper nutrient coupling...
September 30, 2016: Science
Alexandre de Mendoza, Jeffery W Jones, Markus Friedrich
Inconsistent conclusions have been drawn regarding the phylogenetic age of the Methuselah/Methuselah-like (Mth/Mthl) gene family of G protein-coupled receptors, the founding member of which regulates development and lifespan in Drosophila. Here we report the results from a targeted homolog search of 39 holozoan genomes and phylogenetic analysis of the conserved seven transmembrane domain. Our findings reveal that the Mth/Mthl gene family is ancient, has experienced numerous extinction and expansion events during metazoan evolution, and acquired the current definition of the Methuselah ectodomain during its exceptional expansion in arthropods...
February 26, 2016: Scientific Reports
Alyson Sujkowski, Brian Bazzell, Kylie Carpenter, Robert Arking, Robert J Wessells
Endurance exercise has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. In addition, long-term exercise reduces the incidence of age-related diseases in humans and in model organisms. Despite these evident benefits, the genetic pathways required for exercise interventions to achieve these effects are still relatively poorly understood. Here, we compare gene expression changes during endurance training in Drosophila melanogaster to gene expression changes during selective breeding for longevity...
August 2015: Aging
Neil Audsley, Rachel E Down
There is an on-going need for the discovery and development of new pesticides due to the loss of existing products through the continuing development of resistance, the desire for products with more favourable environmental and toxicological profiles and the need to implement the principles of integrated pest management. Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behaviour, including reproduction, osmoregulation, growth and development. Modifying normal receptor function by blocking or over stimulating its actions may either result in the death of a pest or disrupt its normal fitness or reproductive capacity to reduce pest populations...
December 2015: Insect Biochemistry and Molecular Biology
Lijun Wang, Yuk Man Li, Lin Lei, Yuwei Liu, Xiaobo Wang, Ka Ying Ma, Zhen-Yu Chen
Cranberry is an excellent source of dietary antioxidants. The present study investigated the effect of cranberry anthocyanin (CrA) extract on the lifespan of fruit flies with focus on its interaction with aging-related genes including superoxide dismutase (SOD), catalase (CAT), methuselah (MTH), insulin receptor (InR), target of rapamycin (TOR), hemipterus (Hep), and phosphoenolpyruvate carboxykinase (PEPCK). Results showed that diet containing 20mg/mL CrA could significantly prolong the mean lifespan of fruit flies by 10% compared with the control diet...
September 2015: Experimental Gerontology
Ashutosh Pandey, Rehana Khatoon, Sanjay Saini, Divya Vimal, Devendra Kumar Patel, Gopeshwar Narayan, Debapratim Kar Chowdhuri
Adverse reports on the exposure of organisms to dichlorvos (DDVP; an organophosphate insecticide) necessitate studies of organismal resistance/tolerance by way of pharmacological or genetic means. In the context of genetic modulation, a mutation in methuselah (mth; encodes a class II G-protein-coupled receptor (GPCR)) is reported to extend (~35%) the life span of Drosophila melanogaster and enhance their resistance to oxidative stress induced by paraquat exposure (short term, high level). A lack of studies on organismal tolerance of DDVP by genetic modulation prompted us to examine the protective efficacy of mth mutation in exposed Drosophila...
June 2015: Free Radical Biology & Medicine
Chengjun Li, Wei Wu, Ming Sang, Xing Liu, Xingxing Hu, Xiaopei Yun, Bin Li
Methuselah-like 1 of Tribolium castaneum (TcMthl1) has been reported to play crucial roles in development, lifespan, stress resistance and reproduction. However, the signaling system of TcMthl1 is unknown. Thus, we compare the transcriptome profile of RNAi treated larvae (ds-Tcmthl1) and control larvae of T. castaneum by RNA-sequencing, and obtained 14,613,514 sequence reads aligned with 13,533 genes; 812 differentially expressed genes (DEGs) were identified. These DEGs were classified into 47 GO functional groups, including such functions as the immune system process, the response to stimulus, the developmental process and reproduction...
September 1, 2014: Gene
Chengjun Li, Yi Zhang, Xiaopei Yun, Yanyun Wang, Ming Sang, Xing Liu, Xingxing Hu, Bin Li
Methuselah (Mth) is associated with lifespan, stress resistance and reproduction in Drosophila melanogaster, but Mth is not present in nondrosophiline insects. A number of methuselah-likes (mthls) have been identified in nondrosophiline insects, but it is unknown whether the functions of mth are shared by mthls or are divergent from them. Five mthls have been identified in Tribolium castaneum. Although they have different developmental expression patterns, they all enhance resistance to starvation. Only mthl1 and mthl2 enhance resistance to high temperature, whereas mthl4 and mthl5 negatively regulate oxidative stress in T...
October 2014: Insect Molecular Biology
Arvind K Shukla, Prakash Pragya, Hitesh S Chaouhan, D K Patel, M Z Abdin, Debapratim Kar Chowdhuri
Parkinson's disease (PD) is a prevalent and devastating neurodegenerative disorder having limited cure options and strong association with the loss of dopaminergic neurons in the substantia nigra region of the mid brain. Etiology of PD includes both genetic and environmental factors. Paraquat (PQ), a widely used herbicide, is known to be associated with pathogenesis of PD. We report that a mutation in Drosophila methuselah (mth(1)), which is associated with aging, has a role in preventing dopaminergic neuronal cell death in PQ-exposed organism...
October 2014: Neurobiology of Aging
Agavni Petrosyan, Oscar F Gonçalves, I-Hui Hsieh, Kourosh Saberi
Methuselah (mth) is a chromosome 3 Drosophila mutant with an increased lifespan. A large number of studies have investigated the genetic, molecular, and biochemical mechanisms of the mth gene. Much less is known about the effects of mth on preservation of sensorimotor abilities throughout Drosophila's lifespan, particularly in late life. The current study investigated functional senescence in mth and its parental-control line (w1118) in two experiments that measured age-dependent changes in flight functions and locomotor activity...
February 2014: Age (2005-)
Carla M Sgrò, Belinda van Heerwaarden, Vanessa Kellermann, Choon W Wee, Ary A Hoffmann, Siu F Lee
Clinal studies are a powerful tool for understanding the genetic basis of climatic adaptation. However, while clines in quantitative traits and genetic polymorphisms have been observed within and across continents, few studies have attempted to demonstrate direct links between them. The gene methuselah in Drosophila has been shown to have a major effect on stress response and longevity phenotypes based largely on laboratory studies of induced mutations in the mth gene. Clinal patterns in the most common mth haplotype and for lifespan (both increasing with latitude) have been observed in North American populations of D...
July 2013: Molecular Ecology
Ana Rita Araújo, Micael Reis, Helder Rocha, Bruno Aguiar, Ramiro Morales-Hojas, Sandra Macedo-Ribeiro, Nuno A Fonseca, David Reboiro-Jato, Miguel Reboiro-Jato, Florentino Fdez-Riverola, Cristina P Vieira, Jorge Vieira
The Drosophila melanogaster G protein-coupled receptor gene, methuselah (mth), has been described as a novel gene that is less than 10 million years old. Nevertheless, it shows a highly specific expression pattern in embryos, larvae, and adults, and has been implicated in larval development, stress resistance, and in the setting of adult lifespan, among others. Although mth belongs to a gene subfamily with 16 members in D. melanogaster, there is no evidence for functional redundancy in this subfamily. Therefore, it is surprising that a novel gene influences so many traits...
2013: PloS One
Joel C Eissenberg
Like our clothes, our chromosomes fray at the edges with age. Some believe that if we could discover a molecular tailor to patch our age-abraded chromosome ends, we could become modern Methuselahs. Notably, cancer cells achieve immortality by protecting their chromosome ends. Drugs that selectively fray the ends of cancer cell chromosomes would be potent and general anti-cancer therapies. Here, I summarize data on the role of chromosome ends in cellular and organismal aging.
January 2013: Missouri Medicine
Yuanyuan Zuo, Cheng Peng, Yintong Liang, Ka Ying Ma, Ho Yin Edwin Chan, Yu Huang, Zhen-Yu Chen
The present study investigated the anti-ageing activity of sesamin and its effect on gene expression of superoxide dismutase (SOD), catalase (CAT), methuselah (Mth) and Rpn11 in Drosophila melanogaster. Results demonstrated that 0.2 % sesamin in diet prolonged the mean lifespan of OR wild fruit flies by 12 %, accompanied by up-regulation of SOD1, SOD2, CAT and Rpn11. Sesamin at 0.2 % in diet also attenuated paraquat-induced neurodegeneration with up-regulation of SOD1, SOD2 and Rpn11 in OR wild fruit flies...
April 2013: Biogerontology
Luis E D Gimenez, Parakashtha Ghildyal, Kathleen E Fischer, Hongxiang Hu, William W Ja, Benjamin A Eaton, Yimin Wu, Steven N Austad, Ravi Ranjan
Ubiquitously reduced signaling via Methuselah (MTH), a G-protein-coupled receptor (GPCR) required for neurosecretion, has previously been reported to extend life and enhance stress resistance in flies. Whether these effects are due to reduced MTH signalling in specific tissues remains unknown. We determined that reduced expression of mth targeted to the insulin-producing cells (IPCs) of the fly brain was sufficient to extend life and enhance oxidative stress resistance. Paradoxically, we discovered that overexpression of mth targeted to the same cells has similar phenotypic effects to reduced expression due to MTH's interaction with β-arrestin, which uncouples GPCRs from their G-proteins...
February 2013: Aging Cell
Yuanyuan Zuo, Cheng Peng, Yintong Liang, Ka Ying Ma, Hongjian Yu, Ho Yin Edwin Chan, Zhen-Yu Chen
Black rice is rich in anthocyanin antioxidants. The present study investigated the lifespan-prolonging activity of black rice extracts (BREs) and its effect on gene expressions of CuZnSOD (SOD1), MnSOD (SOD2), catalase (CAT), methuselah (Mth) and Rpn11 involved in the antioxidant system and ageing of fruit flies. The OR wild type fly was maintained on a control diet or two experimental diets containing 10 mg ml(-1) BRE (BRE10) or 30 mg ml(-1) BRE (BRE30). Results demonstrated that BRE30 could prolong the mean lifespan of fruit flies by 14%, accompanied with up-regulation of mRNA SOD1, SOD2, CAT and Rpn11, and with down-regulation of Mth...
December 2012: Food & Function
Meghna V Patel, Dana A Hallal, Jeffery W Jones, Denise N Bronner, Rami Zein, Jason Caravas, Zahabiya Husain, Markus Friedrich, Mark F A Vanberkum
Functional studies of the methuselah/methuselah-like (mth/mthl) gene family have focused on the founding member mth, but little is known regarding the developmental functions of this receptor or any of its paralogs. We undertook a comprehensive analysis of developmental expression and sequence divergence in the mth/mthl gene family. Using in situ hybridization techniques, we detect expression of six genes (mthl1, 5, 9, 11, 13, and 14) in the embryo during gastrulation and development of the gut, heart, and lymph glands...
July 2012: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
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