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Category :
Languages : en
Pages :
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Book Description
I have assessed longevity in a collection of 1332 co-isogenic gene-trap P-element insertion lines and determined changes in life span of each insert line relative to a corresponding control line. After a secondary screen to validate an effect on phenotype, 58 insert lines were significant for an increase in life span. Starvation resistance, chill coma recovery time and climbing activity were measured on these lines to identify pleiotropic effects. A positive correlation was found for males between life span and starvation resistance as well as between life span and chill coma recovery. Females only displayed a correlation between life span and chill coma recovery, which was negative. None of the lines indicated increased fitness for all phenotypes, indicating there may be some type of trade-off. There also appears to be a lot of pleiotropic variation depending on background and sex. Ten of the lines, all with the same parental background, were chosen for a half-diallel cross to identify epistasis between the mutants. There were substantial epistatic interactions between all ten lines. Furthermore, males and females displayed vastly different patterns of epistasis, again indicating major differences in life span regulation between the sexes. Finally, a subset of seven of the lines used in the epistatic study, in addition to the corresponding parental control, were chosen for microarray analysis to look for possible pathways and novel genes involved in increasing life span. 1,996 probe sets were significant at a false discovery rate q-value threshold of q d"0.0001. Tukeys tests were carried out for these probe sets to determine how each of the seven mutant backgrounds differed compared to the control and each other. In addition, each mutant background was compared individually with the control to identify any changes in expression. Gene ontologies were determined for each of the lines to identify over-represented biological functions which would indicate possibl.
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Category :
Languages : en
Pages :
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Book Description
I have assessed longevity in a collection of 1332 co-isogenic gene-trap P-element insertion lines and determined changes in life span of each insert line relative to a corresponding control line. After a secondary screen to validate an effect on phenotype, 58 insert lines were significant for an increase in life span. Starvation resistance, chill coma recovery time and climbing activity were measured on these lines to identify pleiotropic effects. A positive correlation was found for males between life span and starvation resistance as well as between life span and chill coma recovery. Females only displayed a correlation between life span and chill coma recovery, which was negative. None of the lines indicated increased fitness for all phenotypes, indicating there may be some type of trade-off. There also appears to be a lot of pleiotropic variation depending on background and sex. Ten of the lines, all with the same parental background, were chosen for a half-diallel cross to identify epistasis between the mutants. There were substantial epistatic interactions between all ten lines. Furthermore, males and females displayed vastly different patterns of epistasis, again indicating major differences in life span regulation between the sexes. Finally, a subset of seven of the lines used in the epistatic study, in addition to the corresponding parental control, were chosen for microarray analysis to look for possible pathways and novel genes involved in increasing life span. 1,996 probe sets were significant at a false discovery rate q-value threshold of q d"0.0001. Tukeys tests were carried out for these probe sets to determine how each of the seven mutant backgrounds differed compared to the control and each other. In addition, each mutant background was compared individually with the control to identify any changes in expression. Gene ontologies were determined for each of the lines to identify over-represented biological functions which would indicate possibl.
Author: Michael Mahlon Magwire
Publisher:
ISBN:
Category :
Languages : en
Pages : 188
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Book Description
Keywords: longevity.
Author: Steven Paul Nilsen
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages :
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Book Description
Analysis of the mechanisms of aging has been advanced by finding single gene mutation which affect life span in model organisms, such as Drosophila melanogaster and C. elegans. Understanding genetic changes associated with age-dependent functional decline are also vital for elucidating the mechanisms of aging, and may predict mutations which affect life span. This study expands on current methods for screening longevity mutations in Drosophila by assaying phenotypic changes in aged adult flies. Several lines of evidence implicate the nervous system as critical to regulation of life span, thus mutations are made via ectopic overexpression of random genes in neural cell lineages using the GAL4-UAS system. The age-dependent behaviors used to assay functional change in aged adults were negative geotaxis response, heat stress sensitivity, and temperature sensitive paralysis. Other recorded phenotypes include lethality, physical defects and increased mortality under normal environmental conditions. 1868 mutations were screened, 36 were lethal and 245 were behaviorally phenotypic. Functional analysis of phenotypic versus non-phenotypic mutations identified gene families affecting age-dependent functional decline by altering neural function. Specific analysis of two mutations demonstrates the utility of the screen in uncovering mutations that change functional decline and life span. A mutation that activated expression of both Aats-asp and NMDA1 demonstrated it was possible to correlate accelerated functional decline with a decrease in life span and slowed functional decline with an increase in lifespan. A different mutation that increased expression of dsc1, a sodium channel homologue, accelerated functional decline and shortened life span when used to affect several different neural populations. However increasing expression in dsc1 in glial cell lineages slowed functional decline and may have increased life span. The results support a glial and non-neural endogenous adult expression pattern of dsc1. Thus, this screen provides a framework for launching further investigations into the mechanisms of physiological aging affecting age-dependent functional decline and possibly mortality.
Author: Alexander M. Vaiserman
Publisher: Springer
ISBN: 3319183265
Category : Medical
Languages : en
Pages : 351
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Book Description
This book looks at aging through research on Drosophila, the fruit fly that is one of the most widely used model organisms in bio gerontology. Work in model organisms can expand the theoretical knowledge of aging: it yields valuable insight into the molecular and cellular processes that underlie aging process, and it can perhaps provide new therapeutic targets for the treatment of age-related disorders in humans. Drosophila models have been developed for a large variety of aging-related processes and diseases, and this book provides readers with an overview of current research on the use of the Drosophila model to understand the genetic, molecular and physiological mechanisms that underlie the aging process. Themes of health span, life extension and longevity-associated genes emerge in this collation of international research on Drosophila that is of relevance to geriatrics and gerontology, animal genetics and genomics, and biomedicine. This fascinating, illustrated book will be of interest to a wide audience, ranging from academic researchers to the general reader.
Author: Hardip Brar Passananti
Publisher: World Scientific
ISBN: 9789812567222
Category : Music
Languages : en
Pages : 510
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Book Description
Methuselah Flies presents a trailblazing project on the biology of aging. It describes research on the first organisms to have their lifespan increased, and their aging slowed, by hereditary manipulation. These organisms are fruit flies from the species Drosophila melanogaster, the great workhorse of genetics. Michael Rose and his colleagues have been able to double the lifespan of these insects, and improved their health in numerous respects as well. The study of these flies with postponed aging is one of the best means we have of understanding, and ultimately achieving, the postponement of aging in humans. As such, the carefully presented detail of this book will be of value to research devoted to the understanding and control of aging. Methuselah Flies: is a tightly edited distillation of twenty years of work by many scientists; contains the original publications regarding the longer-lived fruit flies; offers commentaries on each of the topics covered - new, short essays that put the individual research papers in a wider context; gives full access to the original data; captures the scientific significance of postponed aging for a wide academic audience.
Author: Caleb E. Finch
Publisher:
ISBN:
Category : Health & Fitness
Languages : en
Pages : 304
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Book Description
Demographers and public health specialists have been surprised by the rapid increases in life expectancy, especially at the oldest ages, that have occurred since the early 1960s. Some scientists are calling into question the idea of a fixed upper limit for the human life span. There is new evidence about the genetic bases for both humans and other species. There are also new theories and models of the role of mutations accumulating over the life span and the possible evolutionary advantages of survival after the reproductive years. This volume deals with such diverse topics as the role of the elderly in other species and among human societies past and present, the contribution of evolutionary theory to our understanding of human longevity and intergenerational transfers, mathematical models for survival, and the potential for collecting genetic material in household surveys. It will be particularly valuable for promoting communication between the social and life sciences.
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Category : Demography
Languages : en
Pages : 312
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Author: Angela Parrish
Publisher:
ISBN:
Category :
Languages : en
Pages : 70
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Author: Robert Arking
Publisher: Oxford University Press
ISBN: 0195167392
Category : Family & Relationships
Languages : en
Pages : 619
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Book Description
Robert Arking's Biology of Aging is an introductory text to the biology of aging which gives advanced undergraduate and graduate students a thorough review of the entire field. The mass of data related to aging is summarized into fifteen focused chapters, each dealing with some particular aspect of the problem. His prior two editions have also served admirably as a reference text for clinicians and scientists. This new edition captures the extraordinary recent advances in our knowledge of the ultimate and proximal mechanisms underlying the phenomenon of aging.
Author: Christian Sell
Publisher: Springer Science & Business Media
ISBN: 160327507X
Category : Medical
Languages : en
Pages : 203
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Book Description
In recent years, remarkable discoveries have been made concerning the underlying mechanisms of aging. In Life-Span Extension: Single-Cell Organisms to Man, the editors bring together a range of illuminating perspectives from researchers investigating the aging process in a variety of species. This novel work addresses the aging process in species ranging from yeast to man and, among other subjects, features detailed discussions of the naked mole-rat, an exceptionally long-lived rodent; the relationship between dietary factors/food restriction and aging; and an evolutionary view of the human aging process. Single mutations that extend life span have been identified in yeast, worms, flies, and mice, whereas studies in humans have identified potentially important markers for successful aging. At the same time, it has been discovered that the genes and pathways identified in these studies involve a surprisingly small set of conserved functions, most of which have been the focus of aging research for some time. For example, the mTOR pathway, a regulator of translation and protein synthesis, has been identified as a common longevity pathway in yeast and Caenorhabditis elegans. In mammals, this pathway intersects with neuroendocrine pathways and with the insulin/insulin-like growth factor pathways, which have been identified as major modulators of life span and aging in both invertebrates and mice. Novel, emerging technologies and the increasingly wide variety of systems that are now used to study aging and the mechanisms of aging provide enormous opportunities for the identification of common pathways that modulate longevity. It is these common pathways that are the focus of this important volume.
