Modulation of aging through mechanisms of nutrient demand and reward

通过营养需求和奖励机制调节衰老

• 批准号: 9005964
• 负责人: SCOTT PLETCHER
• 金额: $ 31.28万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9005964
• 关键词: Affect; Afferent Neurons; Aging; Amino Acids; Animal Model; Animals; Behavior; Behavioral; Biological; Biological Models; Biology of Aging; Brain; Brain region; Caenorhabditis elegans; Cells; Complex; Corticotropin-Releasing Hormone; Creativeness; Data; Decision Making; Dementia; Diet; Disease; Diuretics; Drosophila genus; Drosophila melanogaster; Elderly; Environment; Evaluation; Feedback; Food; Food Preferences; Genes; Growth; Health; Health Benefit; Homologous Gene; Hormones; Hour; Human; Hunger; Individual; Insulin; Intake; Intervention; Ion Channel; Laboratories; Lead; Life; Link; Longevity; Malignant Neoplasms; Mammals; Maps; Metabolic; Metabolism; Molecular; Molecular Genetics; Mus; Nature; Nervous system structure; Neurobiology; Neurologic; Neurons; Neuropeptides; Nutrient; Nutritional; Organism; Outcome; Output; Pain; Partner in relationship; Pathology; Pathway interactions; Peripheral; Phenotype; Physiological; Physiology; Play; Population; Prevalence; Process; Proteins; Regulation; Reporting; Reproduction; Research; Rewards; Risk Factors; Role; Saccharomyces cerevisiae; Satiation; Sensory; Serotonin; Signal Pathway; Signal Transduction; Societies; Starvation; Stress; System; TRP channel; Taste Perception; Taxon; Testing; Tissues; Work; age related; detection of nutrient; dietary manipulation; experience; fly; functional decline; genetic analysis; health economics; healthy aging; innovation; insight; loss of function; mortality; neural circuit; novel; preference; protein intake; public health relevance; relating to nervous system; response; sensory input; sensory system; serotonin receptor; success; tool

 DESCRIPTION (provided by applicant): Unrelenting growth in the number of elderly in our society and the resulting impact on the prevalence of age- related disease will have dramatic economic and health-related consequences over the next two decades. Although the causes and consequences of many diseases, including cancer and dementia, are slowly being unraveled, the mechanisms that underlie advanced age as the most significant risk factor associated with these disease states are relatively unknown. This is an important issue because single interventions that impact mechanisms of aging would be expected to ameliorate or eliminate multiple pathologies and diseases. We are, therefore, not just talking about extending lifespan; advances in understanding the basic biology of aging would have tremendous general health benefits as well. Our understanding of mammalian aging has been greatly stimulated over the past decade by research in simple model systems. Arguably, today's most effective aging-related interventions in mice target sirtuin genes, as well as TOR and insulin/IGF signaling pathways, all of which were first identified in Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster. In recent years, modern molecular genetics, often using simple model organisms, has provided a well-defined biological framework for understanding the causes and consequences of decision-making. Information entering the brain from canonical sensory systems and internal homeostatic mechanisms is received, integrated, and dispatched to orchestrate changes in peripheral tissues. We believe that these 'decisions' are important modulators of aging. More specifically, our hypothesis is that specific mechanisms that evaluate internal and external nutrient availability and initiate physiological changes associated with states such as hunger and satiety play important roles in the modulation of behavior and lifespan. Harnessing the neurobiology of simple model systems to study the impact of how physiological decisions are made in response to evaluated energy status will yield insights into the broad influence of nutrients on longevity across taxa, includin humans. It will also provide an understanding of the molecular details about how neuronal inputs orchestrate cell-autonomous and non-autonomous mechanisms to insure survival and health in a complex organism. The innovative nature of this proposal, which derives from the uniquely appropriate tools available in Drosophila together with a novel perspective about the importance of evaluative and sensory influences on lifespan, provides the creativity and experimental power to develop and test hypotheses about the cell non-autonomous control of aging that have not been previously considered. In addition to providing an opportunity to discover basic mechanisms of aging, our work may also lead to creative intervention strategies that ameliorate aging-related functional decline in humans.