Ageing Lessons From C Elegans

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.

Using the most well-studied behavioral analyses of animal subjects to promote a better understanding of the effects of disease and the effects of new therapeutic treatments on human cognition, Methods of Behavior Analysis in Neuroscience provides a reference manual for molecular and cellular research scientists in both academia and the pharmaceutic

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].

Featuring extensive references, updated for this paperback edition, Longevity, Senescence, and the Genome constitutes a landmark contribution to biomedicine and the evolutionary biology of aging. To enhance gerontology's focus on human age-related dysfunctions, Caleb E. Finch provides a comparative review of all the phyla of organisms, broadening gerontology to intersect with behavioral, developmental, evolutionary, and molecular biology. By comparing species that have different developmental and life spans, Finch proposes an original typology of senescence from rapid to gradual to negligible, and he provides the first multiphyletic calculations of mortality rate constants.

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.

The molecular genetics of aging or life-span determination is an expanding field. One reason is because many people would consider it desirable if hu man life span could be extended. Indeed, it is difficult not to be fascinated by tales of the life and death of people who have succeeded in living a very long life. Because of this, we have placed at the head of this book the chapter by Perls et al. on Centenerians and the Genetics of Longevity. Perls and his coauthors convincingly argue that, while the average life expectancy might be mostly determined by environmental factors because the average person has an average genotype, extremely long life spans are genetically determined. Of course, studying humans to uncover the genetics of aging is not ideal, not so much because one cannot easily perform experiments as because they live such a long time. This is why most of this book describes the current state of research with model organisms such as yeast, worms, flies, and mice. J aswinski focuses on yeast and how metabolic activity and stress resistance affect the longevity of Saccharomyces cerevisiae. In the process, he discusses the concept of aging as applied to a unicellular organism such as yeast and the importance of metabolism and stress resistance for aging in all organisms.

Defines the current status of research in the genetics, anatomy, and development of the nematode C. elegans, providing a detailed molecular explanation of how development is regulated and how the nervous system specifies varied aspects of behavior. Contains sections on the genome, development, neural networks and behavior, and life history and evolution. Appendices offer genetic nomenclature, a list of laboratory strain and allele designations, skeleton genetic maps, a list of characterized genes, a table of neurotransmitter assignments for specific neurons, and information on codon usage. Includes bandw photos. For researchers in worm studies, as well as the wider community of researchers in cell and molecular biology. Annotation copyrighted by Book News, Inc., Portland, OR

Comprehensive Overview of Advances in Olfaction The common belief is that human smell perception is much reduced compared with other mammals, so that whatever abilities are uncovered and investigated in animal research would have little significance for humans. However, new evidence from a variety of sources indicates this traditional view is likely overly simplistic. The Neurobiology of Olfaction provides a thorough analysis of the state-of-the-science in olfactory knowledge and research, reflecting the growing interest in the field. Authors from some of the most respected laboratories in the world explore various aspects of olfaction, including genetics, behavior, olfactory systems, odorant receptors, odor coding, and cortical activity. Until recently, almost all animal research in olfaction was carried out on orthonasal olfaction (inhalation). It is only in recent years, especially in human flavor research, that evidence has begun to be obtained regarding the importance of retronasal olfaction (exhalation). These studies are beginning to demonstrate that retronasal smell plays a large role to play in human behavior. Highlighting common principles among various species – including humans, insects, Xenopus laevis (African frog), and Caenorhabditis elegans (nematodes) – this highly interdisciplinary book contains chapters about the most recent discoveries in odor coding from the olfactory epithelium to cortical centers. It also covers neurogenesis in the olfactory epithelium and olfactory bulb. Each subject-specific chapter is written by a top researcher in the field and provides an extensive list of reviews and original articles for students and scientists interested in further readings.