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Ageing: Lessons from C. elegans

Ageing: Lessons from C. elegans
Author: Anders Olsen
Publisher: Springer
Total Pages: 433
Release: 2016-12-06
Genre: Medical
ISBN: 3319447033

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This book brings together in one volume the current state of ageing research in the nematode Caenorhabditis elegans. The authors are leading researchers in the field, placing this topic in the context of human ageing, describing how and why basic discoveries in this simple organism have impacted our prospects for intervention in the ageing process. The authors cover a broad range of topics with regards to organismal and reproductive ageing including anatomical, physiological and biochemical changes, as well as genetic and environmental interventions that promote longevity and ameliorate age-related disease. Ageing is the single most important factor determining the onset of human disease in developed countries. With current worldwide demographic trends indicating that the number of individuals over the age of 65 will continue to rise, it is clear that an understanding of the processes that underpin ageing and age-related disease represents a key challenge in the biomedical sciences. In recent years there have been huge advances in our understanding of the ageing process and many of these have stemmed from genetic analysis of C. elegans. With no analogous book in this subject area this work will be of interest to a wide audience, ranging from academic researchers to the general public.


Comparative Biology of Aging

Comparative Biology of Aging
Author: Norman S. Wolf
Publisher: Springer Science & Business Media
Total Pages: 397
Release: 2010-01-08
Genre: Medical
ISBN: 904813465X

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determined by an inability to move in response to touch. C. elegans develop through four larval stages following hatching and prior to adulthood. Adult C. elegans are reproductive for about the rst week of adulthood followed by approximately two weeks of post-reproductive adulthood prior to death. Life span is most commonly measured in the laboratory by maintaining the worms on the surface of a nutrie- agar medium (Nematode Growth Medium, NGM) with E. coli OP50 as the bacterial food source (REF). Alternative culture conditions have been described in liquid media; however, these are not widely used for longevity studies. Longevity of the commonly used wild type C. elegans hermaphrodite (N2) varies ? from 16 to 23 days under standard laboratory conditions (20 C, NGM agar, E. coli OP50 food source). Life span can be increased by maintaining animals at lower ambient temperatures and shortened by raising the ambient temperature. Use of a killed bacterial food source, rather than live E. coli, increases lifespan by 2–4 days, and growth of adult animals in the absence of bacteria (axenic growth or bac- rial deprivation) increases median life span to 32–38 days [3, 23, 24]. Under both standard laboratory conditions and bacterial deprivation conditions, wild-derived C. elegans hermaphrodites exhibit longevity comparable to N2 animals [25].


Aging of Organisms

Aging of Organisms
Author: H.D. Osiewacz
Publisher: Springer Science & Business Media
Total Pages: 278
Release: 2013-11-11
Genre: Science
ISBN: 9401706719

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Biological aging as the time-depending general decline of biological systems associated with a progressively increasing mortality risk is a general phenomenom of great significance. The underlying processes are very complex and depending on genetic and environment factors. These factors encode or affect a network of interconnected cellular pathways. In no system this network has been deciphered in greater detail. However, the strategy of studying various biological systems has let to the identification of pathways and specific modules and makes it obvious that aging is the result of different overlapping mechanisms and pathways. Some of these appear to be conserved ("public") among species, others are specific or "private" and only of significance in one or a few organisms. This volume in the series on "Biology of aging and its modulation" specifically focuses on organismic aging. The book covers research on organisms from lower to higher complexity representing examples from very diverse taxa like photosynthetic plants, fungi, sponges, nematodes, flies, birds and mammals. Such a broad treatise of this complex topic provides a comprehensive "flavor" about the current issues dealt with in this rapidly growing scientific discipline.


Neuronal Inputs and Outputs of Aging and Longevity

Neuronal Inputs and Outputs of Aging and Longevity
Author: Joy Alcedo
Publisher: Frontiers
Total Pages: 136
Release: 2013-08-23
Genre:
ISBN: 2889191605

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An animal’s survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environments. This is achieved through intercellular communication not only within a single tissue but also among different tissues and organ systems. Thus, alterations in tissue-to-tissue or organ-to-organ communications, which are under genetic regulation, can affect organismal homeostasis, and consequently impact the aging process. One of the organ systems that play a major role in maintaining homeostasis is the nervous system. Considering that the nervous system includes the sensory system, which perceives the complexity of an animal’s environment, it should be no surprise that there would be a sensory influence on homeostasis and aging. To promote homeostasis, any given sensory information is transmitted through short-range signals via neural circuits and/or through long-range endocrine signals to target tissues, which may in turn be neuronal or non-neuronal in nature. At the same time, since homeostasis involves a number of feedback mechanisms, non-neuronal tissues can also modulate sensory and other neuronal functions. Several genes that regulate signaling pathways known to affect homeostasis and aging have been shown to act in neurons, in tissues that are likely downstream targets of the nervous system, or through feedback regulation of neuronal activities. These genes can have different temporal requirements: some might function early, e.g., by affecting neural development, while others may only be required later in adulthood. Some well-known examples of genes involved in the neuronal regulation of homeostasis and longevity encode components of the evolutionarily conserved nutrient-sensing insulin/insulin-like signaling pathway, the stress-sensing internal repair system, and the mitochondrial electron transport chain. Indeed, the genetic perturbation of these pathways has been found to lead to numerous diseases, many of which are age-related and involve the nervous system, such as neurodegeneration and the metabolic syndrome. Despite much progress, however, many aspects of the neuronal inputs and outputs that affect aging and longevity are poorly understood to date. For example, the precise neuronal and non-neuronal circuitries and the details of the molecular mechanisms through which genes/signaling pathways maintain homeostasis and affect aging in response to the environment remain to be elucidated. Similarly, it is presently unclear whether genes that regulate the early development of the nervous system and its consequent circuitry influence homeostasis and longevity during adulthood. At the same time, although many genes affecting aging are conserved, both the nervous system and the aging process are highly variable within populations and among taxa. Accordingly, the role of natural genetic variation in shaping the neurobiology of aging is also presently unknown. The aim of this Research Topic is therefore to highlight the genetic, developmental, and physiological aspects of the signaling networks that mediate the neuronal inputs and outputs that are required to maintain organismal homeostasis. The elucidation of the effects of these neuronal activities on homeostasis may thus provide much-needed insight into mechanisms that affect aging and longevity.


A Living Model for Obesity and Aging Research

A Living Model for Obesity and Aging Research
Author: Peiyi Shen
Publisher:
Total Pages:
Release: 2018
Genre:
ISBN:

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Caenorhabditis elegans (C. elegans) is a free-living nematode that has been extensively utilized as an animal model for the research involving aging and neurodegenerative diseases, like Alzheimer and Parkinson, etc. Compared with the traditional animal models, this nematode possesses many benefits, such as small body size, short lifespan, complete sequenced genome and more than 65% of the genes associated with human diseases. All these characteristics enable this organism to be an ideal living system for obesity and aging studies. Piceatannol is a natural stilbene with many beneficial effects, such as anti-oxidative, anti-inflammatory, anti-atherogenic activities, however, its role on fat accumulation and aging of whole organism is not known. Our results showed that piceatannol (50 and 100 [mu]M) significantly reduced fat accumulation of wild type worms grown in normal and high glucose conditions without altering the growth rate, worm length, pumping rate, or moving speed. The current study further indicated that piceatannol decreased the expression of sbp-1 (encodes an ortholog of mammalian sterol-regulatory-element-binding protein) and its target gene fasn-1 (encodes fatty acid synthase) as well as increased the expression of hosl-1 (encodes an ortholog of hormone-sensitive lipase) in glucose-treated worms. These data suggested that piceatannol reduced fat accumulation in C. elegans by suppression of genes involved in lipid synthesis and possibly through stimulation of lipolysis. Furthermore, piceatannol (50 and 100 [mu]M) significantly extended the lifespan of C. elegans and delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. The current study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires the insulin/IGF-1 signaling (IIS) pathway and sir-2.1 (encodes sirtuin). Research has shown that permethrin, a Type-I pyrethroid, increases triglyceride (fat) accumulation in adipocytes. Little is known, however, about any similar effect of deltamethrin, a Type-II pyrethroid, which produces a distinct syndrome of poisoning in mammals compared with permethrin. Our study indicated that deltamethrin (10 [mu]M) significantly increased the fat accumulation in wild type C. elegans and concomitantly reduced the total progeny number and locomotive activities in a dose-dependent manner. Deltamethrin increased fat accumulation via aak-2 (an ortholog of AMPK[alpha]) and nhr-49 (downstream target of aak-2 with function close to peroxisome proliferator-activated receptor-a) mediated mechanisms. The current study may have important implications in understanding effect of bioactive compounds as well as insecticides on the regulation of fat storage and healthy aging in humans.


Longitudinal Studies of Caenorhabditis Elegans Aging and Behavior Using a Microfabricated Multi-well Device

Longitudinal Studies of Caenorhabditis Elegans Aging and Behavior Using a Microfabricated Multi-well Device
Author: Matthew Alexander Churgin
Publisher:
Total Pages: 0
Release: 2017
Genre:
ISBN:

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The roundworm C. elegans is a powerful model organism for dissecting the genetics of behavior and aging. The central genetic pathways regulating lifespan, such as insulin signaling, were first identified in worms. C. elegans is also the only animal for which a full map of all neural synpatic connections, or connectome, exists. However, current manual and automated methods are unable to efficiently monitor and quantify behavioral phenotypes which unfold over long time scales. Therefore, it has been difficult to study phenotypes such as long-term behavior states and behavioral changes with age in worms. To address these limitations, here I describe a novel device, called the WorMotel, to longitudinally monitor behavior in up to 240 single C. elegans on time scales encompassing the worm's maximum lifespan of two months. The WorMotel is fabricated from polydimethylsiloxane from a 3-D printed negative mold. Each device consists of 240 individual wells, each of which houses a single worm atop agar and bacterial food. I use custom software to quantify movement between frames to longitudinally monitor behavior for each animal. I first describe the application of the WorMotel to the automation of lifespan measurements in C. elegans, the characterization of intra-strain and inter-strain variability in behavioral decline, the relationship between behavior and lifespan, and the scaling of behavioral decline with increasing stress. I then describe the application of the WorMotel to quantify locomotive behavioral states and their modulation by the presence or absence of food as well as biogenic amine neurotransmitters. Using the WorMotel in combination with genetics and pharmacology, I outline a neural circuit by which the biogenic amines serotonin and octopamine regulate locomotion state to signal animals to adopt behavior appropriate to a fed and fasting state, respectively. I include protocols for construction of custom imaging rigs and requirements for long-term imaging as an appendix. The WorMotel is a powerful tool that can facilitate discovery and understanding of the mechanisms underlying long-term phenotypes such as behavioral states and aging.


Metabolic Control of Aging in C. Elegans

Metabolic Control of Aging in C. Elegans
Author: Wen Gao
Publisher:
Total Pages: 201
Release: 2018
Genre:
ISBN: 9789462998858

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Aging is a complex process that is characterized by a physiological decline at the cellular and tissue level and it is associated with many diseases. So far, several hallmarks of aging have been identified, and many of them have emphasized the important role of metabolism in the aging process. The objective of this thesis is to elucidate the role of metabolic processes involved in aging. To explore this, we developed a platform for metabolomics analysis in nematode C. elegans, and measured metabolic consequences of in aging models as well as the interactions between genes and the environment (G x E). In order to study the metabolic consequence related to the aging process, I developed and validated a sensitive mass-spectrometry (MS)-based platform for metabolomics studies in C. elegans. This platform was applied in the following three chapters of the thesis and allowed us to investigate metabolic consequence related to aging in different angles. In Chapter 4, We directly compared two long-lived mutant strains, i.e. daf-2 (impaired IIS pathway) and eat-2 (CR model), by whole-genome microarray and MS platforms. In Chapter 5, we studied the contribution of genetic factors on metabolite levels in a natural population of C. elegans and identified several fatty acid metabolism genes. In Chapter 6, we used a candidate gene approach to study the effect of G x E interaction on metabolic process and aging. In the final chapter of this thesis, Chapter 7 and Chapter 8, I summarized all chapters and provided concluding remarks and future perspectives.