京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18646号 / 医博第3945号 / 新制||医||1006(附属図書館) / 31560 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川上 浩司, 教授 横出 正之, 教授 千葉 勉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Adolescence is an important developmental period for executive function as well as establishing lifelong health habits like diet and exercise. However, connections between exercise, executive function and dietary behaviors have not yet been adequately studied in adolescents, especially in terms of exercise duration. This research seeks to establish how 30 versus 60 minutes of exercise affects the association between executive function, calorie consumption and food-specific inhibition. The current research uses a within-participant design and linear mixed modeling to test the impact of exercise bout duration and executive function on calorie consumption and food-specific inhibition (food Go/No-Go accuracy and reaction time). This paper concludes that for adolescents, there may be a small impact of EF on dietary behaviors. It also concludes that 30 versus 60 minutes of non-cognitively demanding exercise (i.e., treadmill running) does not affect these associations in meaningful ways. Overall, the practical advantages of 30 minutes versus 60 minutes of exercise may make this a better recommendation for teens, but additional research on the impact of exercise is needed to inform these recommendations.

Acetyl-CoA is a metabolite at the crossroads of central metabolism and the substrate of histone acetyltransferases regulating gene expression. In many tissues fasting or lifespan extending calorie restriction (CR) decreases glucose-derived metabolic flux through ATP-citrate lyase (ACLY) to reduce cytoplasmic acetyl-CoA levels to decrease activity of the p300 histone acetyltransferase (HAT) stimulating pro-longevity autophagy. Because of this, compounds that decrease cytoplasmic acetyl-CoA have been described as CR mimetics. But few authors have highlighted the potential longevity promoting roles of nuclear acetyl-CoA. For example, increasing nuclear acetyl-CoA levels increases histone acetylation and administration of class I histone deacetylase (HDAC) inhibitors increases longevity through increased histone acetylation. Therefore, increased nuclear acetyl-CoA likely plays an important role in promoting longevity. Although cytoplasmic acetyl-CoA synthetase 2 (ACSS2) promotes aging by decreasing autophagy in some peripheral tissues, increased glial AMPK activity or neuronal differentiation can stimulate ACSS2 nuclear translocation and chromatin association. ACSS2 nuclear translocation can result in increased activity of CREB binding protein (CBP), p300/CBP-associated factor (PCAF), and other HATs to increase histone acetylation on the promoter of neuroprotective genes including transcription factor EB (TFEB) target genes resulting in increased lysosomal biogenesis and autophagy. Much of what is known regarding acetyl-CoA metabolism and aging has come from pioneering studies with yeast, fruit flies, and nematodes. These studies have identified evolutionary conserved roles for histone acetylation in promoting longevity. Future studies should focus on the role of nuclear acetyl-CoA and histone acetylation in the control of hypothalamic inflammation, an important driver of organismal aging.

<div> <div> <div> <p>Recent studies using data from the National Health and Nutrition Examination Survey (NHANES) have used inconsistent approaches to identify and categorize beverages, especially those containing low-calorie sweeteners (LCS), also referred to as low-calorie sweetened beverages (LCSB). Herein, we investigate the approaches used to identify and categorize LCSB in recent analyses of NHANES data. We reviewed published studies examining LCS consumption in relation to dietary and health outcomes and extracted the methods used to categorize LCS as reported by the authors of each study. We then examined the extent to which these approaches reliability identified LCSBs using the Internet Archive Wayback Machine to examine beverage ingredients lists across 3 NHANES cycles (2011-2016). None of the four general strategies appeared to include all LCSB while also excluding all beverages that did not contain LCS. In some cases, the type of sweetener in the beverage consumed could not be clearly determined; we found 9, 16, and 18 of such “mixed” beverage identifiers in 2011-12, 2013-14, and 2015-15, respectively. Then, to illustrate how heterogeneity in beverage categorization may impact the outcomes of published analyses, we compared results of a previously published analysis with outcomes when “mixed” beverages were grouped either all as LCSB or all as sugary beverages. Our results suggest that caution is warranted in design and interpretation of studies using NHANES data to examine dietary and health correlates of sweetened beverage intake. </p> </div> </div> </div>

No description available.

The purpose of this study was to determine if post-operative serum albumin and percentage of weight loss improved in patients who received formalized pre-operative nutrition counseling. Nutrition intervention was measured quantitatively. A retrospective review of records was conducted on 77 RYGB patients (68 female subjects and 9 male subjects), ages 21-64, during January 2001 through January 2006. The results indicated that patients who received pre-operative nutrition intervention had better clinical outcomes of serum albumin than those with no nutrition intervention from a registered dietitian. However, outcomes regarding percentage of weight loss varied. Both pre-operatively and at the 3 month post-operative visit the weight of subjects who received nutrition intervention seemed to be increasing by the 6 month post-operative visit the subjects with no nutrition intervention had lost more weight.

Genome-wide studies of diseases and chronic conditions frequently fail to uncover marked or consistent differences in RNA or protein concentrations. However, the developing field of kinetic proteomics has made promising discoveries in differences in the turnover rate of these same proteins, even when concentrations were not necessarily different. The situation can theoretically be modeled mathematically using bifurcation equations, but uncovering the proper form of these is difficult. To this end, we developed TWIG, a method for characterizing bifurcations that leverages information geometry to identify drivers of complex systems. Using this, we characterized the bifurcation and stability properties of all 132 possible 3- and 22,662 possible 4-node subgraphs (motifs) of protein-protein interaction networks. Analyzing millions of real world protein networks indicates that natural selection has little preference for motifs that are stable per se, but a great preference for motifs who have parameter regions that are exclusively stable, rather than poorly constrained mixtures of stability and instability. We apply this knowledge to mice on calorie restricted (CR) diets, demonstrating that changes in their protein turnover rates do indeed make their protein networks more stable, explaining why CR is the most robust way known to extend lifespan.

No description available.

The normal aging process in humans is characterized by a number of hallmark changes including decreased white matter volume in the brain and accompanying cognitive decline. This is in contrast to neurodegenerative aging processes which involve acute pathology which results in neuronal cell death. Studying non-degenerative normal aging in humans can be difficult because of the high prevalence of neurodegenerative diseases in the population and other potentially confounding effects. Rhesus monkeys are an excellent model organism for the study of normal aging, as their aging process has been demonstrated to involve diminished white matter volume, but they do not suffer from neurodegenerative diseases such as Alzheimer's. In this study we seek to quantify levels of myelin degradation using confocal microscopy in regions of interest where it has been previously demonstrated that loss of white matter integrity results in lower levels of cognitive function across different treatment groups including aging monkeys, calorie restricted monkeys, and controls for calorie restricted monkeys. These areas include prefrontal white matter which is vital to executive function, the hippocampus which is integral to memory consolidation and the learning process, and finally the anterior, middle, and posterior cingulum bundle. The cingulum bundle contains a diverse variety of projections between cortical and subcortical regions, including but not limited to projections to and from the cingulate cortex which has been demonstrated to be vital for emotional processing, the limbic system, and a wide spectrum of other functions. We aim to quantify white matter degradation in these regions by using immunofluorescent tagging for healthy myelin basic protein (MBP) and degraded myelin basic protein (dMBP) and by measuring the colocalization between the two. For prefrontal white matter and hippocampus, we did not find significant differences in myelin degradation across treatment groups. In the cingulum bundle, however, we did find a significant effect of treatment on overall myelin damage throughout the bundle, and in particular we determined that there was a significant difference in colocalization in the anterior cingulum bundle between aging monkeys and control calorie restricted monkeys. Analysis of behavioral testing data yielded surprising results as we were unable to find a strong correlation between our measure for myelin degradation, and level of cognitive impairment. Our results indicate that there are likely differences in regional vulnerability to age related myelin damage across different white matter regions of the brain, however we would like to expand on this study to gain a more accurate understanding of how loss of white matter volume is distributed through the brain and the impact that has on cognitive outcomes.

Aging is the major risk factor for chronic age-related diseases characterized by loss of homeostasis, organ dysfunction, and inflammation. Calorie restriction (CR) has been shown to slow aging and delay the onset of chronic age-related diseases. Even though CR has many positive health effects, the degree and duration of the restriction needed would reduce the intervention's usefulness and make it challenging to start and maintain in humans. The difficulties brought on by CR have led to the development of CR mimetics that can mimic the effects of CR without reducing food intake (in an ad libitum state). We hypothesize that in PEPCK bovine Growth Hormone (bGH) overexpressing transgenic mice with accelerated metabolic and cognitive aging, the health span and phenotypes of aging can be improved by adding CR mimetics, a combination of lipoic acid, nicotinamide, thiamine, pyridoxine, and piperine to the diet. From 10 to 40 weeks of age, bGH-tg mice and their normal (N) littermates were fed CRM diet ad libitum. Normal littermates and bGH-tg mice fed a standard chow diet served as controls. Evaluation of the effects of CRM included insulin and glucose tolerance tests (ITT and GTT), indirect calorimetry as well as rotarod, working memory, grip strength testing. Body weight and percent fat mass were significantly lower, but percent lean mass was significantly higher in mice on a CRM diet at 40 weeks. At 19 weeks, insulin sensitivity was improved considerably in treated N and bGH-tg males. At 20 weeks of age, all mice on a CRM diet had significantly improved glucose tolerance and lower fasting glucose. At week 32, treated N female mice had significantly higher energy expenditure during the day and night per gram of body weight. In treated N males, this was true only during the day. Male bGH-tg mice on CRM diet had decreased energy expenditure during the night. Insulin sensitivity was significantly improved in treated male N and bGH-tg mice at week 37. Week 38 GTT showed enhanced glucose tolerance and lower fasting glucose in all mice on a CRM diet except Tg females. Week 39-40 Y-maze, rotarod and grip strength testing showed improved motor coordination and grip strength in all mice on CRM diet with no difference in working memory. Also, there was a significant improvement in metabolic and aging phenotype with lowered pro-inflammatory cytokines at the gene and protein levels in various tissues. Our study indicates the employed CRM produce the beneficial health effects in short-lived, insulin resistant bGH Tg mice but the effects are time-, sex-, genotype-, and diet-dependent. Most of the effects of this intervention resemble the effects of CR suggesting that employed compounds may act via similar mechanisms. This work was funded by the SIU-SOM Geriatrics Research Initiative (AB), NIA R01AG068288, and the Hillblom Foundation (PK).