This project will develop the microcrustacean Daphnia as a model system for the biology of aging. Daphnia are freshwater microcrustaceans that reproduce through cyclic parthenogenesis, allowing laboratory investigators to generate thousands of genetically identical individuals easily. Biodemographic and physiological methods for quantifying genetic variation of lifespan and rates of aging will be coupled with analyses of genome-wide gene expression and the development of transgenic individuals. The goal is to establish a model system where information on aging can be integrated from molecular, cellular, physiological and demographic approaches and placed in the context of known ecological pressures exerted on aging and on the response to available resources. The proposed work includes A) characterization of aging in TCO, the Daphnia pulex clone whose entire genome has been sequenced, B) characterization of aging in a genetically diverse collection of new isolates from the field, C) characterization of the response to dietary restriction in the TCO clone and new isolates, D) application of whole-genome microarray technology to quantify global patterns of age-dependency in gene expression in TCO and new isolates, E) investigation of the scale and pattern of changes in age-dependent gene expression induced by dietary restriction, F) identification of novel genes and pathways with age- dependent regulation or whose expression is predictive of lifespan, G) development of a technique for heritable transformation of live Daphnia, H) overexpression of key genes involved in pathways known to regulate the effects of dietary restriction on aging, and I) observation of aging and response to dietary restriction in Daphnia clones where key genes have been overexpressed. PUBLIC HEALTH RELEVANCE: Aging is the progressive decline of bodily faculties as individuals grow older. The development of new model organisms to understand the biology of aging allows for a broader understanding of the genetic mechanisms and consequences of potential interventions, such as dietary restriction, that reduce the negative effects of aging. In this work, a new model organism, Daphnia, is developed through the identification of genetic variants with different rates of aging, identification of genes with age-dependent expression, and determination of the effects of key genes on aging processes.