TitleAnalysis of EGF signaling in healthy aging promotion in caenorhabditis elegans
NameYu, Shih-Hung (author), Padgett, Richard (chair), Driscoll, Monica (internal member), Pintar, John (internal member), Singson, Andrew (outside member), Rutgers University, Graduate School - New Brunswick,
Aging--Animal models ,
DescriptionThe increase in longevity expectancy has been a focused issue goal of much current aging research. Many genes have been noted to modulate longevity of simple model systems, acting through distinct mechanisms. However, in principle, promotion of healthy aging of individual tissues can be accomplished without a major impact on the longevity endpoint. As such, healthspan-only genes may have been missed by genetic screens for longevity. New screens for tissue–specific betterment of aging phenotypes were anticipated to reveal a class of genes that might be manipulated for tissue-specific anti-aging outcomes. We identified two novel healthspan regulators, called HPA-1 and HPA-2 (for the high performance in old age locomotory phenotypes that their disruption confers) that delay age-associated locomotory decline when they are knocked down by RNAi or by genetic deletion. Surprisingly, hpa-1 and hpa-2 do not regulate healthspan through canonical recognized longevity pathways. Instead, the structure of HPA proteins implicated a novel function of EGF signaling in anti–aging protection, and my genetic studies supported this mechanism. Activated EGF signaling confers a positive effect on multiple aging phenotypes, acting through the downstream branch of the EGF pathway involving PLCanalysis defined the temporal and spatial benefits from EGF signaling. EGF/lin-3 ligand is expressed into late life and acts throughout life to influence healthy aging. lin-3 alternative slice variants, lin-3S and lin-3XL show healthspan promotion. Muscle and neuron are the most potent tissue for EGFR signaling on healthspan enhancement. I also identified global and tissue-specific modulators of healthy aging in the EGF pathway and identified candidate calcium-sensitive transducers of the anti-aging function of EGF signaling. Recent data in vertebrates suggest that EGF signaling might contribute to long-term maintenance. Thus, EGF signaling may exert a conserved impact on healthy aging and might be a plausible reagent for anti-aging therapies.
NoteIncludes bibliographical references
Noteby Shih-Hung Yu
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.