Aging in appendaged bacteria

Trustees Of Indiana University, Bloomington IN

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Abstract

DESCRIPTION (provided by applicant): Recent research demonstrates that bacteria deteriorate with age, as indicated by declining reproductive output. These findings open up an exciting new avenue of research on the evolution and physiology of aging, providing a potential analog for aging in eukaryotes and a means for identifying universal features of aging. Furthermore, aging mechanisms in bacteria offer particular promise for understanding and mitigating mitochondrial deterioration, potentially improving the quality and duration of human life. However, the physiological qualities of older bacteria and the mechanism(s) of age-specific decline remain undetermined. We hypothesize that asymmetrical damage segregation during reproduction promotes age-specific deterioration via damage accumulation in aging cells. Furthermore, we propose that reproductive asymmetry facilitates efficient elimination of damage from a cell population. This study provides a detailed analysis of the aging process in two closely related, appendaged bacteria, Hyphomonas neptunium and Caulobacter crescentus. These organisms, including known Caulobacter asymmetry mutants, provide a comparative model system for evaluating the hypothesized consequences of reproductive asymmetry. Specific Aims Determine the degree of reproductive asymmetry diverse C. crescentus strains and in H. neptunium Quantify the effects of asymmetry on cellular damage accumulation and aging in C. crescentus and H. neptunium Fluorescent labeling of macromolecules will permit detailed examination of cellular trafficking between mother and daughter cells, thereby establishing the degree of reproductive asymmetry in allocation of potentially damaged biomolecules in various bacterial strains. Measures of reproductive rate, RNA expression, protein expression, and oxidative damage will then assess physiological changes between birth and late life in order to determine correlations between agings and described reproductive asymmetries. PUBLIC HEALTH RELEVANCE: These experiments provide the first detailed analysis of the mechanism(s) and physiology of bacterial aging. This research aims to identify the mechanistic basis for bacterial aging, thereby determining the generality of aging mechanisms identified previously in humans and other organisms. Detailed understanding of bacterial aging offers potential strategies for slowing the aging process in humans. Aging mechanisms in bacteria may also provide drug targets for treating bacterial infection.