Although DNA repair capacity has been correlated with lifespan in terrestrial vertebrate species, it remains unknown how evolutionarily conserved the process is across all vertebrate taxa. In particular, chondrichthyan fishes have lifespans that range from 3-350 years and they are evolutionarily separated from modern humans Homo sapiens by approximately 400 million years. We hypothesized that chondrichthyan fishes would show significant homology in nuclear excision repair (NER) genes with humans, and that the expression of NER genes will correlate with the lifespan of the respective assessed species. For this study, DNA repair gene homology and expression was performed on the nurse shark Ginglymostoma cirratum (n=3) and yellow stingray Urobatis jamaicensis (n=3). The five main NER pathways were analyzed and compared to see the differences in both elasmobranch species, then compared with human foreskin fibroblast samples (n=3). RNA sequencing was used to determine the extent of gene expression in each species, comparing the read counts in each gene and comparing between the two species. The elephant shark Callorhinchus milii reference genome was used to align the nurse shark and yellow stingray samples. Homology of each gene of the NER pathways was assessed by the NCBI BLAST software. Results show that the MMR pathway has all the significant genes in higher frequencies in the nurse shark than in human. Within elasmobranchs in the five DNA repair pathways, the longer-lived species (nurse shark) has a significant higher gene expression than shorter-lived species (yellow stingray). Genes involved in the NER and BER pathways showed significantly lower expression in elasmobranch than in humans. However, there were significantly higher expression of more genes for the HR and MMR pathways in elasmobranchs than in humans.

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mRNA molecules form an intermediate in the transfer of sequences from DNA to ribosomes in order to guide protein production. Errors can be introduced into mRNA, producing aberrant proteins which place a strain on cellular regulatory machinery, causing increased risks of apoptosis, cancer, and decreased fitness. These errors may be introduced due to decreased transcriptional proofreading capabilities, exposure to chemicals, or mistakes in RNA editing machinery. It is important to investigate these causes of transcription errors to better understand the long-neglected area of mRNA fidelity which has such significant impacts on our cellular functions. In this paper, it was determined that addition of adenine opposite from abasic sites, not genomic uracil pairing with adenine, are a probable cause of G-to-A transcription errors. That exposure to Roundup causes increased levels of transcription errors, potentially due to oxidative stress. And finally, that off-target ADAR gene editing of transcripts occurs at high levels.

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This thesis investigates the link between optimal carbon tax and endogenous longevity. It considers an overlapping generation model with clean and dirty intermediate goods. Externality caused by producing dirty intermediate goods damages the final goods productionas well as the agents’ longevity. From the social planner’s problem, the cost of carbon emission is formulated. Then, the Pigouvian carbon tax rate is used to internalize such costs. With the two channels of impact of carbon emission combined, the theoretical results suggest that (i) the current carbon tax may abstract from local health costs of carbon emission, especially in rich economies, (ii) in poor economies, the government may be lowering the carbon tax at the expense of their elderly’s welfare, and (iii) the government in economies transitioning from poverty to richness should raise their carbon tax level above that of poor economies. Deeper investigation into the mechanism and a quantitative analysis would beneeded. Future studies can also include endogenous technological change or extend to amulti-economy model.

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Globally, increased length-of-life trends parallel the rise in reported levels of loneliness. Social connectedness is associated with a 50% reduced risk of premature mortality, and research has shown there is a moderately strong association between people who are lonely and people who have an unmet desire to belong. As so, urban planners and designers continually try to understand place relationships within communities to better the health and welfare of future generations. This thesis acknowledges there is a gap of understanding how the built and natural environment play a role in an increased sense of belonging, thus contributing to an alleviation of reported feelings of loneliness and potentially increasing length and quality of life. Utilizing the ‘Blue Zone’ island of Ikaria as a case study, where residents commonly live well beyond 90 and 100 years, this thesis aims to better understand connections between longevity and the physical environment for the longest-lived, cataloguing how these connections influence feelings of belonging. The research consists of a site visit to Ikaria, Greece, where data was collected over the period of five days, employing interview and field observation methods. Drawing from key concepts within environmental psychology and placemaking, the work critically explores the perceptions of Ikarian elders and the public space they regularly inhabit, as well as their role in contributing to sense of place and feelings of belonging. The conclusion offers suggestions on how urban planners might take these findings into consideration, as it is of great importance for planning professionals to better understand individual perceptions of their environment, which may help prevent alienation and increase overall wellbeing.

京都大学 / 新制・課程博士 / 博士(理学) / 甲第23744号 / 理博第4834号 / 新制||理||1691(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 工藤 洋, 准教授 本庄 三恵, 教授 松下 智直 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

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