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C elegans aging

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https://www.readbyqxmd.com/read/28940623/genetic-interaction-with-temperature-is-an-important-determinant-of-nematode-longevity
#1
Hillary Miller, Marissa Fletcher, Melissa Primitivo, Alison Leonard, George L Sutphin, Nicholas Rintala, Matt Kaeberlein, Scott F Leiser
As in other poikilotherms, longevity in C. elegans varies inversely with temperature; worms are longer-lived at lower temperatures. While this observation may seem intuitive based on thermodynamics, the molecular and genetic basis for this phenomenon is not well understood. Several recent reports have argued that lifespan changes across temperatures are genetically controlled by temperature-specific gene regulation. Here, we provide data that both corroborate those studies and suggest that temperature-specific longevity is more the rule than the exception...
September 21, 2017: Aging Cell
https://www.readbyqxmd.com/read/28934747/untangling-longevity-dauer-and-healthspan-in-caenorhabditis-elegans-insulin-igf-1-signalling
#2
Collin Yvès Ewald, Jorge Iván Castillo-Quan, T Keith Blackwell
The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C...
September 22, 2017: Gerontology
https://www.readbyqxmd.com/read/28934392/nceh-1-modulates-cholesterol-metabolism-and-protects-against-%C3%AE-synuclein-toxicity-in-a-c-elegans-model-of-parkinson-s-disease
#3
Siyuan Zhang, Samantha A Glukhova, Kim A Caldwell, Guy A Caldwell
Parkinson's disease (PD) is an aging-associated neurodegenerative disease affecting millions worldwide. Misfolding, oligomerization and accumulation of the human α-synuclein protein is a key pathological hallmark of PD and is associated with the progressive loss of dopaminergic neurons over the course of aging. Lifespan extension via the suppression of IGF-1/insulin-like signaling (IIS) offers a possibility to retard disease onset through induction of metabolic changes that provide neuroprotection. The nceh-1 gene of Caenorhabditis elegans encodes an ortholog of neutral cholesterol ester hydrolase 1 (NCEH-1), an IIS downstream protein that was identified in a screen as a modulator of α-synuclein accumulation in vivo...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28919364/forward-and-reverse-genetics-approaches-to-uncover-metabolic-aging-pathways-in-caenorhabditis-elegans
#4
REVIEW
Arwen W Gao, Jelmi Uit de Bos, Mark G Sterken, Jan E Kammenga, Reuben L Smith, Riekelt H Houtkooper
The biological mechanisms of aging have been studied in depth and prominent findings in this field promote the development of new therapies for age-associated disorders. Various model organisms are used for research on aging; among these, the nematode Caenorhabditis elegans has been widely used and has provided valuable knowledge in determining the regulatory mechanisms driving the aging process. Many genes involved in lifespan regulation are associated with metabolic pathways and are influenced by genetic and environmental factors...
September 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28915791/segmentation-and-classification-of-two-channel-c-elegans-nucleus-labeled-fluorescence-images
#5
Mengdi Zhao, Jie An, Haiwen Li, Jiazhi Zhang, Shang-Tong Li, Xue-Mei Li, Meng-Qiu Dong, Heng Mao, Louis Tao
BACKGROUND: Aging is characterized by a gradual breakdown of cellular structures. Nuclear abnormality is a hallmark of progeria in human. Analysis of age-dependent nuclear morphological changes in Caenorhabditis elegans is of great value to aging research, and this calls for an automatic image processing method that is suitable for both normal and abnormal structures. RESULTS: Our image processing method consists of nuclear segmentation, feature extraction and classification...
September 15, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28915560/pharynx-mitochondrial-ca-2-dynamics-in-live-c-elegans-worms-during-aging
#6
Pilar Alvarez-Illera, Paloma García-Casas, Jessica Arias-Del-Val, Rosalba I Fonteriz, Javier Alvarez, Mayte Montero
Progressive decline in mitochondrial function is generally considered one of the hallmarks of aging. We have expressed a Ca(2+) sensor in the mitochondrial matrix of C. elegans pharynx cells and we have measured for the first time mitochondrial [Ca(2+)] ([Ca(2+)]M) dynamics in the pharynx of live C. elegans worms during aging. Our results show that worms stimulated with serotonin display a pharynx [Ca(2+)]M oscillatory kinetics that includes both high frequency oscillations (up to about 1Hz) and very prolonged "square-wave" [Ca(2+)]M increases, indicative of energy depletion of the pharynx cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912432/mitigating-motor-neuronal-loss-in-c-elegans-model-of-als8
#7
Wendy Zhang, Antonio Colavita, Johnny K Ngsee
ALS8 is a late-onset familial autosomal dominant form of Amyotrophic Lateral Sclerosis (ALS) caused by a point mutation (P56S) in the VAPB gene (VAMP associated protein isoform B). Here, we generated two C. elegans models of the disease: a transgenic model where human VAPB wild-type (WT) or P56S mutant was expressed in a subset of motor neurons, and a second model that targeted inducible knockdown of the worm's orthologue, vpr-1. Overexpression of human VAPB in DA neurons caused a backward locomotion defect, axonal misguidance, and premature neuronal death...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882853/neuronal-inhibition-of-the-autophagy-nucleation-complex-extends-life-span-in-post-reproductive-c-elegans
#8
Thomas Wilhelm, Jonathan Byrne, Rebeca Medina, Ena Kolundžić, Johannes Geisinger, Martina Hajduskova, Baris Tursun, Holger Richly
Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including pha-4 Through downstream analysis of pha-4, we identified that the inactivation of genes governing the early stages of autophagy up until the stage of vesicle nucleation, such as bec-1, strongly extend both life span and health span...
September 7, 2017: Genes & Development
https://www.readbyqxmd.com/read/28878670/daf-16-foxo-transcription-factor-in-aging-and-longevity
#9
REVIEW
Xiaojuan Sun, Wei-Dong Chen, Yan-Dong Wang
Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signaling pathway, TOR signaling, AMPK pathway, JNK pathway and germline signaling have been found to be involved in aging and longevity. And DAF-16/FOXO, as a key transcription factor, could integrate different signals from these pathways to modulate aging, and longevity via shuttling from cytoplasm to nucleus...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28857552/precision-electrophile-tagging-in-caenorhabditis-elegans
#10
Marcus J C Long, Daniel A Urul, Shivansh Chawla, Hong-Yu Lin, Yi Zhao, Joseph A Haegele, Yiran Wang, Yimon Aye
Adduction of an electrophile to privileged sensor proteins and the resulting phenotypically dominant responses are increasingly appreciated as being essential for metazoan health. Functional similarities between the biological electrophiles and electrophilic pharmacophores commonly found in covalent drugs further fortify the translational relevance of these small-molecule signals. Genetically encodable or small-molecule-based fluorescent reporters and redox proteomics have revolutionized the observation and profiling of cellular redox states and electrophile-sensor proteins, respectively...
September 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28854356/multilayered-reprogramming-in-response-to-persistent-dna-damage-in-c-%C3%A2-elegans
#11
Diletta Edifizi, Hendrik Nolte, Vipin Babu, Laia Castells-Roca, Michael M Mueller, Susanne Brodesser, Marcus Krüger, Björn Schumacher
DNA damage causally contributes to aging and age-related diseases. Mutations in nucleotide excision repair (NER) genes cause highly complex congenital syndromes characterized by growth retardation, cancer susceptibility, and accelerated aging in humans. Orthologous mutations in Caenorhabditis elegans lead to growth delay, genome instability, and accelerated functional decline, thus allowing investigation of the consequences of persistent DNA damage during development and aging in a simple metazoan model. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28844646/counteracting-ascarosides-act-through-distinct-neurons-to-determine-the-sexual-identity-of-c-%C3%A2-elegans-pheromones
#12
Erin Z Aprison, Ilya Ruvinsky
Sex pheromones facilitate reproduction by attracting potential mates and altering their behavior and physiology. In C. elegans, males and hermaphrodites secrete similar blends of pheromone molecules, two of which are present in different relative concentrations: ascr#3, which is more abundant in hermaphrodites, and ascr#10, which is more abundant in males. It is not currently understood how this compositional difference results in sex-specific effects, for example, the slower aging of the hermaphrodite germline in the presence of physiologically relevant concentrations of male pheromones...
September 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28840220/microfluidic-systems-for-high-throughput-and-high-content-screening-using-the-nematode-caenorhabditis-elegans
#13
REVIEW
Matteo Cornaglia, Thomas Lehnert, Martin A M Gijs
In a typical high-throughput drug screening (HTS) process, up to millions of chemical compounds are applied to cells cultured in well plates, aiming to find molecules that exhibit a robust dose-response, as evidenced for example by a fluorescence signal. In high-content screening (HCS), one goes a step further by linking the tested compounds to phenotypic information, obtained, for instance, from microscopic cell images, thereby creating richer data sets that also require more advanced analysis methods. The nematode Caenorhabditis elegans came into the screening picture due to the wide availability of its mutants and human disease models, its relatively easy culture and short life cycle...
August 25, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28839194/an-automated-compound-screening-for-anti-aging-effects-on-the-function-of-c-elegans-sensory-neurons
#14
Daphne Bazopoulou, Amrita R Chaudhury, Alexandros Pantazis, Nikos Chronis
Discovery of molecular targets or compounds that alter neuronal function can lead to therapeutic advances that ameliorate age-related neurodegenerative pathologies. Currently, there is a lack of in vivo screening technologies for the discovery of compounds that affect the age-dependent neuronal physiology. Here, we present a high-throughput, microfluidic-based assay for automated manipulation and on-chip monitoring and analysis of stimulus-evoked calcium responses of intact C. elegans at various life stages...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835694/coherent-raman-imaging-of-live-muscle-sarcomeres-assisted-by-sfg-microscopy
#15
Hyunmin Kim, Do-Young Kim, Kyung-Il Joo, Jung-Hye Kim, Soon Moon Jeong, Eun Seong Lee, Jeong-Hoon Hahm, Kyuhyung Kim, Dae Woon Moon
In this study, we used spectrally focused coherent anti-Stokes Raman scattering (spCARS) microscopy assisted by sum-frequency generation (SFG) to monitor the variations in the structural morphology and molecular vibrations of a live muscle of Caenorhabditis elegans. The subunits of the muscle sarcomeres, such as the M-line, myosin, dense body, and α-actinin, were alternatively observed using spCARS microscopy for different sample orientations, with the guidance of a myosin positional marker captured by SFG microscopy...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28831863/emodin-extends-lifespan-of-caenorhabditis-elegans-through-insulin-igf-1-signaling-pathway-depending-on-daf-16-and-sir-2-1
#16
Xuan Zhao, Lulu Lu, Yonghao Qi, Miao Li, Lijun Zhou
The naturally occurring anthraquinone emodin has been serving primarily as an anti-bacterial and anti-inflammatory agent. However, little is known about its potential on anti-aging. This investigation examined the effect of emodin on lifespan and focused on its physiological molecular mechanisms in vivo. Using Caenorhabditis elegans (C. elegans) as an animal model, we found emodin could extend lifespan of worms and improve their antioxidant capacity. Our mechanistic studies revealed that emodin might function via insulin/IGF-1 signaling (IIS) pathway involving, specifically the core transcription factor DAF-16...
October 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28827345/indoles-from-commensal-bacteria-extend-healthspan
#17
Robert Sonowal, Alyson Swimm, Anusmita Sahoo, Liping Luo, Yohei Matsunaga, Ziqi Wu, Jui A Bhingarde, Elizabeth A Ejzak, Ayush Ranawade, Hiroshi Qadota, Domonica N Powell, Christopher T Capaldo, Jonathan M Flacker, Rhienallt M Jones, Guy M Benian, Daniel Kalman
Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28817671/immunohistochemical-analysis-reveals-variations-in-proteasome-tissue-expression-in-c-elegans
#18
Elisa Mikkonen, Caj Haglund, Carina I Holmberg
The ubiquitin-proteasome system (UPS) plays a crucial part in normal cell function by mediating intracellular protein clearance. We have previously shown that UPS-mediated protein degradation varies in a cell type-specific manner in C. elegans. Here, we use formalin-fixed, paraffin-embedded C. elegans sections to enable studies on endogenous proteasome tissue expression. We show that the proteasome immunoreactivity pattern differs between cell types and within subcellular compartments in adult wild-type (N2) C...
2017: PloS One
https://www.readbyqxmd.com/read/28814374/from-bench-laboratory-to-bed-hospital-home-how-to-explore-effective-natural-and-synthetic-pak1-blockers-longevity-promoters-for-cancer-therapy
#19
REVIEW
Hiroshi Maruta, Mok-Ryeon Ahn
PAK family kinases are RAC/CDC42-activated kinases that were first found in a soil amoeba 4 decades ago, and 2 decades later, were discovered in mammals as well. Since then at least 6 members of this family have been identified in mammals. One of them called PAK1 has been best studied so far, mainly because it is essential not only for malignant cell growth and metastasis, but also for many other diseases/disorders such as diabetes (type 2), AD (Alzheimer's disease), hypertension, and a variety of inflammatory or infectious diseases, which definitely shorten our lifespan...
August 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28808619/gastrointestinal-parasites-in-captive-and-free-ranging-cebus-albifrons-in-the-western-amazon-ecuador
#20
Sarah Martin-Solano, Gabriel A Carrillo-Bilbao, William Ramirez, Maritza Celi-Erazo, Marie-Claude Huynen, Bruno Levecke, Washington Benitez-Ortiz, Bertrand Losson
Currently, there is a lack of surveys that report the occurrence of gastrointestinal parasites in the white-headed capuchin monkey (Cebus albifrons). We therefore assessed the presence and richness (= number of different parasite genera) of parasites in C. albifrons in wildlife refuges (n = 11) and in a free-ranging group near a human village (n = 15) in the Ecuadorian Amazon. In the 78 samples collected (median of 3 samples per animal), we identified a total of 6 genera of gastrointestinal parasites, representing protozoa, nematodes, acanthocephalans and cestodes...
December 2017: International Journal for Parasitology. Parasites and Wildlife
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