The extension of life span by caloric restriction has been studied across species from yeast and Caenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. From nematodes to mice, extension of life span results from decreased signaling through the insulin/insulin-like growth factor receptor signaling (IIS) pathway. Decreased IIS diminishes phosphatidylinositol (3,4,5) triphosphate (PIP3) production, leading to reduced PI3K and AKT kinase activity and decreased forkhead box O transcription factor (FOXO) phosphorylation, allowing FOXO proteins to remain in the nucleus. In the nucleus, FOXO proteins increase the transcription of genes encoding antioxidant enzymes, including superoxide dismutase 2, catalase, glutathione peroxidase, and hundreds of other genes. An effective method for combating free radical damage occurs through the metabolism of ketone bodies, ketosis being the characteristic physiological change brought about by caloric restriction from fruit flies to primates. A dietary ketone ester also decreases circulating glucose and insulin leading to decreased IIS. The ketone body, d-β-hydroxybutyrate (d-βHB), is a natural inhibitor of class I and IIa histone deacetylases that repress transcription of the FOXO3a gene. Therefore, ketosis results in transcription of the enzymes of the antioxidant pathways. In addition, the metabolism of ketone bodies results in a more negative redox potential of the NADP antioxidant system, which is a terminal destructor of oxygen free radicals. Addition of d-βHB to cultures of C. elegans extends life span. We hypothesize that increasing the levels of ketone bodies will also extend the life span of humans and that calorie restriction extends life span at least in part through increasing the levels of ketone bodies. An exogenous ketone ester provides a new tool for mimicking the effects of caloric restriction that can be used in future research. The ability to power mitochondria in aged individuals that have limited ability to oxidize glucose metabolites due to pyruvate dehydrogenase inhibition suggests new lines of research for preventative measures and treatments for aging and aging-related disorders.

Idag äger en stor del av befolkningen en mobiltelefon. Dessa tillverkas, konsumeras och slängs i stor utsträckning och konsumtionsmönstret visar på en kort livslängd för mobiltelefoner. Tillverkningen leder till farliga utsläpp, och uttjänta mobiltelefoner tas inte alltid om hand på bästa sätt. Detta tär på både miljö och natur, vilket var motiveringen till att utföra denna studie. Målet med studien var att identifiera vilka kategorier av mjukvaruproblem som leder till att mobiltelefoner ersätts. Dessutom undersöks mjukvarans roll till att mobiltelefoner ersätts i relation till sociala faktorer och hårdvarurelaterade problem. Detta gjordes genom en kvalitativ intervjustudie med ett varierat urval på tjugo personer. Identifierade kategorier som lett till ersättning av mobiltelefon är: Skada på hårdvara, Batteri, Prestanda, Annan mobiltelefon, Erbjudande, Slutade uppdateras, och Lagringsutrymme. Kategorier för mjukvarurelaterade problem som identifierats är: Prestanda, Användarvänlighet, Energiförbrukning, Bugg, Påtvingad funktionalitet, Otillgänglig funktionalitet, och Mjukvarustorlek. För framtida forskning föreslås kvantitativa studier för validering av vårt resultat för ett större, representativt, urval. / Today, a large part of the population owns a mobile phone. These are manufactured, consumed and disposed to a large extent, and the consumption pattern shows a short lifetime for mobile phones. Manufacturing leads to dangerous emissions, and the disposal of mobile phones are not always taken care of in the best way, which causes harm to the environment and nature. Seeing how this is a big problem is the reason to why this study has been carried out. The aim of the study was to identify the categories of software problems that are behind the replacement of mobile phones. In addition, the software’s role in the replacement of mobile phones in relation to social factors and hardware problems was investigated. This was done through a qualitative interview study with a varied selection of twenty people. Identified categories that led to mobile phone replacement are: Hardware damage, Battery, Performance, Other mobile phone, Offer, Discontinued updates, and Storage space. Identified categories for software-related issues include: Performance, User-friendliness, Energy consumption, Bug, Enforced functionality, Inaccessible functionality, and Software size. For future research we suggest quantitative studies for validating our results using a larger, representative sample of respondents.

La plasticité cérébrale donne l’opportunité à chaque individu de maximiser son fonctionnement cognitif via l’adoption de comportements enrichis (i.e., théorie de l’enrichissement cognitif). Suivant cette perspective, nous avons articulé dans le cadre de ce travail doctoral des hypothèses inhérentes au rôle modérateur du style de vie sur le déclin cognitif tout au long de la vie adulte, et avons observé le rôle du sexe dans cette relation. La contribution scientifique de ce travail se manifeste au travers de la création et la validation d’un outil de mesure du style de vie (étude 2), et de deux études observationnelles portant (i) sur l’activité physique (étude 1) et (ii) sur le style de vie global (étude 3). Les résultats de cette thèse mettent en évidence l’existence de différents patterns influant sur le vieillissement cognitif, ainsi qu’un important rôle modérateur du sexe dans la relation entre style de vie et déclin cognitif lié à l’âge. Plus précisément, les résultats montrent que le style de vie global, ainsi que les dimensions incluant les relations sociales, les activités physiques pratiquées à long terme et les autres activités de loisirs, sont efficaces pour freiner le vieillissement cognitif chez les femmes uniquement. Si les sollicitations cognitives ne permettent pas, quant à elles, de ralentir la courbe du déclin cognitif, elles influencent de manière positive les performances cognitives tant chez les femmes que chez les hommes. Ce travail doctoral atteste que le style de vie peut représenter un moyen efficace pour lutter contre les effets délétères liés à l’avancée en âge, et permettre non seulement d’ajouter des années à la vie, mais aussi de la vie aux années. / Cerebral plasticity provides an opportunity for each individual to maximize his/her cognitive performance through the adoption of enriched behaviors (i.e., Cognitive Enrichment Theory). From this perspective, we had articulated work hypotheses inherent to the moderating role of lifestyle on the age-related cognitive decline throughout adult lifespan, and we observed the role of sex in this relationship. The scientific contribution of this work occurred through the creation and validation of a lifestyle questionnaire (study 2) and two observational studies about (i) physical activity (study 1) and (ii) the general lifestyle (study 3). Results of this thesis showed the existence of different models influencing cognitive aging, as well as an important moderating role of sex in the relationship between lifestyle and age-related cognitive decline. More specifically, results highlighted that general lifestyle, as well as dimensions including social relationships, long-term physical activities and other leisure activities, were effective for cognitive aging in women only. While cognitive solicitations did not show to slow down the cognitive decline, they had a positive influence on cognitive performances in both women and men. This PhD demonstrated that lifestyle can be an effective way to combat the deleterious effects of aging and could not only add years to life, but also add life to years.

Nearly all multicellular organisms show changes in redox balance with aging leading to oxidative damage of macromolecules. This study investigated the role of the [NADP+]/[NADPH] redox couple in aging. This redox couple plays an important role in maintaining tissue redox balance and becomes slightly more oxidized in aged tissues. NADPH is a major source of reducing equivalents for enzymes that detoxify hydrogen peroxide. However, catalase detoxifies hydrogen peroxide independently of NADPH. But catalase is absent from mitochondria, a major source of hydrogen peroxide, where instead glutathione plays the major role in hydrogen peroxide detoxification in an NADPH-dependent manner. Three major cytoplasmic and three major mitochondrial NADPH generating enzymes were knocked down by the RNAi feeding technique in C. elegans, but little to no significant effects on lifespan were observed. The C. elegans genome contains two predicted, yet uncharacterized, NAD kinase (NADK) genes nadk-1 and nadk-2 to synthesize NADP+. Data suggest that NADK-1 is cytoplasmic, while NADK-2 is mitochondrial. NADK activity assays strongly suggested that both NADK-1 and NADK-2 possess NADK activity. Knockdown of NADKs did not affect the rate of body bending in young nematodes. However, knockdown of nadk-2 in nadk-1 mutant worms slightly decreased lifespan. Deficiency of NADKs increased the [NADP+]/[NADPH] and decreased the [NAD+]/[NADH], similar to redox changes that occur with aging. Unexpectedly, nadk-1 or nadk-2 knockdown resulted in decreased reactive oxygen species (ROS) levels and increased survival in young adult nematodes in the presence of juglone, a superoxide generator. The antioxidant response generated upon NADK knockdown required the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1 in nadk-2 knockdown nematodes, but only required HSF-1 in nadk-1 knockdown nematodes. NADK-1 or NADK-2 deficiency led to increased catalase activity and a strong trend for increased cytoplasmic catalase-1 (ctl-1) gene expression. Peroxisomal catalase-2 (ctl-2) mutant worms showed increased SOD activity when either NADK gene was knocked down, while ctl-1 mutant worms showed increased glutathione peroxidase or glutathione reductase activities following NADK knockdown. In summary, NADK knockdown oxidizes the [NADP+]/[NADPH] to compromise the antioxidant system, but young nematodes are able to mount a compensatory broad antioxidant response leading to decreased ROS levels.

No description available.

No description available.

No description available.

No description available.

Indigenous youth are overrepresented within homelessness and form approximately 20 percent of the total youth homeless population in Canada that uses emergency shelters. While extensive studies have been conducted and new practices have been put in place in an effort to reduce the number of individuals experiencing homelessness, the number of Indigenous youth journeying into homelessness continues to increase. This suggests that the solutions implemented to date have inadequately addressed the needs of Indigenous youth and the situations integral to their worlds. The purpose of this research was to explore Indigenous youths’ experiences of homelessness that promote positive identity development. It used a community-based Indigenous methodology. Building on research by Indigenous and non-Indigenous academics with the stories of Indigenous homeless youth, this research was centered at the intersection of Indigenous youth homelessness and their engagement in behaviours affected by past and present events that impact their processes of identity development. With its strengths-based lens, it deepens understandings of how Indigenous homeless youth create prosocial outcomes that bolster their self-esteem and encourage positive identity development that will support them in young adulthood and stages beyond. Indigenous youth prosocial outcomes must include holistic health outcomes that encompass spiritual, physical, mental and emotional well-being. Ultimately, this research challenges existing conversations held in society regarding Indigenous youths’ behaviours exhibited in homelessness and contributes to Indigenous resurgence, equitable colonial-Indigenous relationships, and reconciliation consistent with the goals put forth in the Truth and Reconciliation Commission of Canada’s recommendations. / Graduate / 2023-08-30

A core construct in the lifespan theory of socioemotional selectivity, future time perspective (FTP) refers to individuals’ perceptions of their remaining time in life. Its adaptation to the work context, occupational future time perspective (OFTP), entails workers’ perceptions of remaining time and opportunities in their careers. Over the past decade, several quantitative studies have investigated antecedents and consequences of general FTP and OFTP in the work context (i.e., FTP at work). We systematically review and critically discuss this literature on general FTP (k = 17 studies) and OFTP (k = 16 studies) and highlight implications for future research and practice. Results of our systematic review show that, in addition to its strong negative relationship with age, FTP at work is also associated with other individual (e.g., personality traits) and contextual variables (e.g., job characteristics). Moreover, FTP at work has been shown to mediate and moderate relationships of individual and contextual antecedents with occupational well-being, as well as motivational and behavioral outcomes. As a whole, findings suggest that FTP at work is an important variable in the field of work and aging, and that future research should improve the ways in which FTP at work is measured and results on FTP at work are reported.