Relationships Between Growth, Aging, and Lifespan

Washington University School Of Medicine, Saint Louis MO

Investigators

Abstract

Aging is a fascinating process that occurs in many plants and animals, including humans. Although aging is extremely important, the causes of aging and the regulation of the aging process are not well characterized. Recently, exciting discoveries regarding genetic and environmental factors that regulate aging have come from studies of the Caenorhabditis elegans nematode worm, and these factors may have evolutionarily conserved roles in vertebrate aging. However, much remains to be learned about how these genetic and environmental factors regulate aging. The experiments in this proposal will address this important issue. The first specific aim is to develop quantitative measures of the growth and aging of somatic and reproductive systems. Longitudinal studies of wild-type animals will be used to characterize the relationships between these processes. In particular, these studies will elucidate the relationships between the growth of somatic and reproductive systems: are there tradeoffs between the growth of different organ systems or do these systems grow in concert? These studies will elucidate the relationships between the aging of somatic and reproductive systems: is the age-related degeneration of one organ dependent or independent of the age-related degeneration of another organ? These studies will elucidate the relationships between growth and aging: does robust growth of somatic or reproductive systems have an eventual cost and result in accelerated aging? Finally, these studies will elucidate how growth and aging of these systems relate to lifespan. The second specific aim is to use these analytic methods to elucidate the mechanisms of lifespan regulation by genetic and environmental factors. Cold temperatures extend the lifespan of many poikilotherm animals, such as C. elegans, and the proposed experiments will characterize the mechanisms of temperature regulation. Genetic analysis of C. elegans has demonstrated that an insulin-like signaling pathway and mitochondrial function significantly affect lifespan regulation. The mechanisms of lifespan regulation will be elucidated by analyzing the relationships between growth and aging in these mutants. Together, these studies will elucidate the aging process in wild-type animals and the regulation of aging by genetic and environmental factors. Intellectual merit of the proposed activity: Aging is a fundamental biological process that remains poorly characterized. The C. elegans model system is well suited to studies of aging, and important insights have already emerged from studies of this organism. By developing quantitative measurements of the growth and aging of somatic and reproductive functions and using longitudinal studies to characterize the relationships between these processes, this proposal is likely to generate substantial insights into the aging process. By using these techniques to characterize environmental and genetic regulation of aging, this proposal is likely to advance the understanding of how the aging process is controlled. Broader impacts resulting from the proposed activity: The proposed experiments will integrate research and teaching and provide opportunities for research training for high school, undergraduate, and graduate students, including individuals from underrepresented groups. This training will contribute to preparing the next generation of scientists in our society. The results of these experiments will be disseminated by publication in scientific journals and be available to the scientific community and the public. Aging has profound affects on individuals, and the aging population has profound affects on society. An understanding of aging may help individuals and society cope with this enormous challenge.