Browsing by Subject "Longevity"
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Item A PRELIMINARY INVESTIGATION INTO THE EXTENDED LIFESPAN OF BAT SPECIES: THE RELATIONSHIP BETWEEN THE EXTRACELLULAR MATRIX PROTEIN HAS2 AND LONGEVITY(2015-06-05) Denham, Aimee N.; Eoff, Shirley M; Ammerman, Loren K; Wilke, RussellInvestigation into physiological and molecular factors influencing the extended lifespan of long-lived species significantly contributes to clinical research aimed at improving the lives of humans. Bats have a significantly longer lifespan than other mammals of similar size and have not been recorded to develop cancer. The longevity and anti-cancer properties displayed by bats are features shared by another well-studied mammal, the naked mole rat. The naked mole rat is currently the longest living rodent with a maximum lifespan of over 30 years, and the species exhibits a novel anti-cancer mechanism involving the rapid production of hyaluronan. The naked mole rat has a unique sequence of hyaluronan synthase 2 (HAS2) which rapidly produces high molecular mass hyaluronan and contributes to reduced activity of hyaluronan degrading enzymes. Known genomic sequences of several species of bats were analyzed to determine differences in amino acid sequence for the HAS2 gene. Furthermore, RNA extracted from captured bats was subjected to real-time polymerase chain reaction to measure the expression level of HAS2 in various tissues. Genomic sequence analysis revealed that the bat species examined did not have the same amino acid substitutions in HAS2 as the naked mole rat. Real-time PCR trials using multiple primers designed to be specific for the HAS2 region resulted in inconclusive data. Therefore, gene expression analysis conclusions cannot be made until successful HAS2 primers are generated to amplify the HAS2 region. Further research needs to be directed towards determining alternative methods to study the longevity and anti-cancer mechanisms bats possess.Item In Pursuit of a Molecular Fountain of Youth: the Identification and Characterization of Lifespan Regulators in Drosophila(2012-07-20) Stenesen, Drew Stanness; Graff, Jonathan M.Over the past century, average human lifespan has experienced steady increase despite lack of substantial intervention or understanding of the aging process. In fact, many organisms have the latent potential to live much longer than they normally do. This indicates lifespan determination is an active process subject to regulation. Components of this impending longevity are beginning to unravel through dietary and genetic studies in model systems. To date, several pathways indicate human lifespan extension through direct molecular intervention may be feasible, however, important limitations persist. A common thread among these conserved lifespan regulators is metabolism. Therefore, further insight into lifespan extending mechanisms may lie within tissues governing important metabolic processes. Here we describe a multi-tiered, strategy to identify Drosophila melanogaster mutants with extended lifespan based upon enrichment for insertions in genes that are expressed in metabolic tissues. Our results indicate metabolically relevant tissues are a rich source of genetic longevity regulation. We identified a regulator of G protein signaling (RGS) domain containing sorting nexin, termed snazarus (sorting nexin lazarus, snz). Flies with insertions into the 5’ untranslated region of snz live up to twice as long as controls. Transgenic expression of UAS-Snz from the snz Gal4 enhancer trap insertion, active in metabolic tissues, rescued lifespan extension. Notably, old snz mutant flies remain active and fertile indicating that snz mutants have prolonged youthfulness, a goal of aging research. Since mammals have snz-related genes, it is possible that the functions of the snz family may be conserved to humans. Next, we identified the two key adenosine monophosphate (AMP) biosynthetic pathways as regulators of Drosophila longevity. We found that heterozygous mutation of anabolic components of the de novo as well as the salvage AMP biosynthesis pathways extend lifespan. These pathway mutations, and caloric restriction, increased adenosine mono- and diphosphate to adenosine triphosphate (ATP) ratios. Consistent with the altered ratios, lifespan extension was dependent on functional adenosine monophosphate-activated protein kinase (AMPK). Supplementing the diets of adult mutants with adenine restored adenosine nucleotide ratios and rescued lifespan extension. These data establish de novo and salvage AMP biosynthesis as determinants of adult lifespan. The dosage sensitivity and enzymatic nature of de novo and salvage AMP biosynthesis, and the conserved aspects of adenosine nucleotide derivatives and lifespan extension, indicate that these pathways are potentially amendable drug targets worth continued exploration. [Keywords: longevity, Drosophila, genetics, aging, metabolism]Item Leadership actions and structures superintendents believe to enhance superintendent longevity : a qualitative study(2014-05) Russell, Susanna Vaulx; Somers, Patricia (Patricia A.)The modern American superintendency faces many challenges, including a national concern that there is a demonstrated shortage of qualified school superintendents in the United States. Reported superintendent tenure ranges from 2.5-4.8 years. Various research and anecdotal data identify and illustrate the complex factors influencing superintendent tenure, and in turn, organizational stability and student achievement. In Texas, superintendents identify strained relationships with the school board president, superintendent/school board communication and relations, and the inability to accomplish goals with the board as significant factors in their length of tenure. Superintendent success in creating and sustaining effective working relationships with his or her boards of trustees and various stakeholder groups is predictive of his or her longevity. Superintendents must successfully navigate interactions with their boards of trustees, as well as internal and external special interest groups, and the greater voting community. Studies abound, regarding causal factors in truncated superintendent tenure, as well as the intrinsic challenges of effectively managing the myriad functions of the superintendency. Those studies primarily focus on interactions with the school board, or describe failed superintendencies from a postmortem perspective. However, the research literature lacks qualitative studies that focus attention on successful superintendent leadership strategies, which have contributed to increased superintendent tenure, and have resulted in increased organizational stability and higher levels of student achievement.Item The stochastic mortality modeling and the pricing of mortality/longevity linked derivatives(2013-05) Chuang, Shuo-Li; Brockett, Patrick; Golden, Linda; MacMinn, Richard D.; Muthuraman, Kumar; Sager, Thomas W.The Lee-Carter mortality model provides the very first model for modeling the mortality rate with stochastic time and age mortality dynamics. The model is constructed modeling the mortality rate to incorporate both an age effect and a period effect. The Lee-Carter model provides the fundamental set up currently used in most modern mortality modeling. Various extensions of the Lee-Carter model include either adding an extra term for a cohort effect or imposing a stochastic process for mortality dynamics. Although both of these extensions can provide good estimation results for the mortality rate, applying them for the pricing of the mortality/ longevity linked derivatives is not easy. While the current stochastic mortality models are too complicated to be explained and to be implemented, transforming the cohort effect into a stochastic process for the pricing purpose is very difficult. Furthermore, the cohort effect itself sometimes may not be significant. We propose using a new modified Lee-Carter model with a Normal Inverse Gaussian (NIG) Lévy process along with the Esscher transform for the pricing of mortality/ longevity linked derivatives. The modified Lee-Carter model, which applies the Lee-Carter model on the growth rate of mortality rates rather than the level of mortality rates themselves, performs better than the current mortality rate models shown in Mitchell et al (2013). We show that the modified Lee-Carter model also retains a similar stochastic structure to the Lee-Carter model, so it is easy to demonstrate the implication of the model. We proposed the additional NIG Lévy process with Esscher transform assumption that can improve the fit and prediction results by adapting the mortality improvement rate. The resulting mortality rate matches the observed pattern that the mortality rate has been improving due to the advancing development of technology and improvements in the medical care system. The resulting mortality rate is also developed under a martingale measure so it is ready for the direct application of pricing the mortality/longevity linked derivatives, such as q-forward, longevity bond, and mortality catastrophe bond. We also apply our proposed model along with an information theoretic optimization method to construct the pricing procedures for a life settlement. While our proposed model can improve the mortality rate estimation, the application of information theory allows us to incorporate the private health information of a specific policy holder and hence customize the distribution of the death year distribution for the policy holder so as to price the life settlement. The resulting risk premium is close to the practical understanding in the life settlement market.