Does aging change docosahexaenoic acid homeostasis? Implications for the challenge to cognitive health in the elderly

Epidemiological studies fairly convincingly suggest that higher intake of fish and omega-3 fatty acids present in fish is associated with reduced risk for age-related cognitive decline (ARCD). Normally, docosahexaenoic acid (DHA) in plasma is positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, ARCD is not consistently associated with lower plasma DHA. Furthermore, DHA is often slightly but significantly higher in plasma and erythrocytes in the elderly without ARCD compared to young adults. Higher plasma DHA in the elderly may be a sign that their fish or DHA intake is higher but we show here that various aspects of DHA homeostasis also change with age. Our supplementation and tracer studies show that DHA metabolism, e.g. transit through the plasma and apparent retroconversion but not beta-oxidation, is different in healthy elderly compared to healthy young adults. Apolipoprotein E4 increases the risk of ARCD, possibly in part because it changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may contribute to making the elderly more susceptible to cognitive decline despite them having similar or sometimes higher plasma DHA than in younger adults. Key words: aging, cognitive decline, dietary, docosahexaenoic acid, omega-3 fatty aci

Plasma incorporation, apparent retroconversion and β-oxidation of 13C-docosahexaenoic acid in the elderly

<p>Abstract</p> <p>Background</p> <p>Higher fish or higher docosahexaenoic acid (DHA) intake normally correlates positively with higher plasma DHA level, but recent evidence suggests that the positive relationship between intake and plasma levels of DHA is less clear in the elderly.</p> <p>Methods</p> <p>We compared the metabolism of ¹³C-DHA in six healthy elderly (mean - 77 y old) and six young adults (mean - 27 y old). All participants were given a single oral dose of 50 mg of uniformly labelled ¹³C-DHA. Tracer incorporation into fatty acids of plasma triglycerides, free fatty acids, cholesteryl esters and phospholipids, as well as apparent retroconversion and β-oxidation of ¹³C-DHA were evaluated 4 h, 24 h, 7d and 28d later.</p> <p>Results</p> <p>Plasma incorporation and β-oxidation of ¹³C-DHA reached a maximum within 4 h in both groups, but ¹³C-DHA was transiently higher in all plasma lipids of the elderly 4 h to 28d later. At 4 h post-dose, ¹³C-DHA β-oxidation was 1.9 times higher in the elderly, but over 7d, cumulative β-oxidation of ¹³C-DHA was not different in the two groups (35% in the elderly and 38% in the young). Apparent retroconversion of ¹³C-DHA was well below 10% of ¹³C-DHA recovered in plasma at all time points, and was 2.1 times higher in the elderly 24 h and 7d after tracer intake.</p> <p>Conclusions</p> <p>We conclude that ¹³C-DHA metabolism changes significantly during healthy aging. Since DHA is a potentially important molecule in neuro-protection, these changes may be relevant to the higher vulnerability of the elderly to cognitive decline.</p

Yucca Mountain Project: FY 2006 Annual Report for Waste Form Testing Activities.

This report describes the experimental work performed at Argonne National Laboratory (Argonne) during fiscal year (FY 2006) under the Bechtel SAIC Company, LLC (BSC) Memorandum Purchase Order (MPO) contract number B004210CM3X. Because this experimental work is focused on the dissolution and precipitation behavior of neptunium, the report also includes, or incorporates by reference, earlier results that are relevant to presenting a more complete understanding of the likely behavior of neptunium under experimental conditions relevant to the Yucca Mountain repository. Important results relevant to the technical bases, validations, and conservatisms in current source term models are summarized. The CSNF samples were observed to corrode following the general contour of the surface rather than via (for instance) grain boundary attack. This supports the current approach of estimating the effective surface area of corroding CSNF based on the geometric surface area of fuel pellet fragments. It was observed that the neptunium and plutonium concentrations in corroded CSNF samples were somewhat higher at and near the corrosion front (i.e., at the interface between the alteration product ''rind'' layer and the underlying fuel) than in the bulk fuel. The neptunium and plutonium at the corrosion front and in the uranyl alteration layer were found to be in the quadravalent (4+) oxidation state. The uranyl phases that constitute most of the alteration rind were depleted in neptunium relative to the bulk fuel: neptunium concentrations in the uranyl alteration rind were less than 20% of that in the parent fuel. Homogeneous precipitation tests have shown that solids precipitate from a 1 x 10{sup -4} M Np(V) solution over the temperature range of 200-280 C, but no evidence was found that any solids precipitated from the same solution at 150 C through 289 days. The solids formed in the homogeneous precipitation tests were predominantly a Np(IV)-bearing phase, probably NpO{sub 2}. The presence of UO{sub 2} resulted in the rapid precipitation at room temperature of similar amounts of Np(IV)- and Np(V)-bearing phases, probably NpO{sub 2} and Np{sub 2}O{sub 5}. Although the UO{sub 2} is presumed to act as a reducing agent for Np(V) that leads to the precipitation of a Np(IV)-bearing phase, the observed formation of a Np(V)-bearing phase suggests that the UO{sub 2} also catalyzes Np{sub 2}O5 precipitation under these test conditions

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline (N = 25) and two (N = 25) and four (N = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (Kglc) declined by 6%–12% mainly in the temporo-parietal lobes and cingulate gyri (p ≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions (p ≥ 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. Kglc in the caudate was directly related to performance on several cognitive tests (r = +0.41 to +0.43, allp ≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to Kglc in the thalamus (r = −0.44, p = 0.04) and in the caudate (r = −0.43, p = 0.05), and also inversely related to executive function, attention and processing speed (r = −0.45 to −0.53, all p ≤ 0.03). We confirm in a longitudinal setting that the age-related decline in Kglc is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac

Plasma response to fish oil in the elderly

Little information is available concerning whether incorporation of dietary omega-3 fatty acids into plasma lipids changes during healthy aging. Elderly (74 ± 4 years old) and young (24 ± 2 years old) adults were given a fish oil supplement for 3 weeks that provided 680 mg/day of docosahexaenoic acid and 320 mg/day of eicosapentaenoic acid, followed by a 2 week wash-out period. Compliance was monitored by spiking the capsules with carbon-13 glucose, the excretion of which was measured in breath CO2. In response to the supplement, plasma docosahexaenoic acid rose 42% more in the elderly but eicosapentaenoic responded similarly in both groups. Despite raising docosahexaenoic acid intake by five to tenfold, the supplement did not raise plasma free docosahexaenoic acid (% or mg/dL) in either group. We conclude that healthy aging is accompanied by subtle but significant changes in DHA incorporation into plasma lipids

Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele

Carrying the apoE ε4 allele (E4+) is the most important genetic risk for Alzheimer's disease. Unlike non-carriers (E4 − ), E4+ seem not to be protected against Alzheimer's disease when consuming fish. We hypothesised that this may be linked to a disturbance in n-3 DHA metabolism in E4+. The aim of the present study was to evaluate [13C]DHA metabolism over 28 d in E4+v. E4 − . A total of forty participants (twenty-six women and fourteen men) received a single oral dose of 40 mg [13C]DHA, and its metabolism was monitored in blood and breath over 28 d. Of the participants, six were E4+ and thirty-four were E4 − . In E4+, mean plasma [13C]DHA was 31 % lower than that in E4 − , and cumulative β-oxidation of [13C]DHA was higher than that in E4 − 1–28 d post-dose (P≤ 0·05). A genotype × time interaction was detected for cumulative β-oxidation of [13C]DHA (P≤ 0·01). The whole-body half-life of [13C]DHA was 77 % lower in E4+ compared with E4 − (P≤ 0·01). In E4+ and E4 − , the percentage dose of [13C]DHA recovered/h as 13CO2 correlated with [13C]DHA concentration in plasma, but the slope of linear regression was 117 % steeper in E4+ compared with E4 − (P≤ 0·05). These results indicate that DHA metabolism is disturbed in E4+, and may help explain why there is no association between DHA levels in plasma and cognition in E4+. However, whether E4+ disturbs the metabolism of 13C-labelled fatty acids other than DHA cannot be deduced from the present study

ANL Technical Support Program for DOE Environmental Restoration and Waste Management. Annual report, October 1990--September 1991

This report provides an overview of progress during FY 1991 for the Technical Support Program that is part of the ANL Technology Support Activity for DOE, Environmental Restoration and Waste Management (EM). The purpose is to evaluate, before hot start-up of the Defenses Waste Processing Facility (DWPF) and the West Valley Demonstration Project (WVDP), factors that are likely to affect glass reaction in an unsaturated environment typical of what may be expected for the candidate Yucca Mountain repository site. Specific goals for the testing program include the following: (1) to review and evaluate available information on parameters that will be important in establishing the long-term performance of glass in a repository environment; (2) to perform testing to further quantify the effects of important variables where there are deficiencies in the available data; and (3) to initiate long-term testing that will bound glass performance under a range of conditions applicable to repository disposal

Kinetics of 13C-DHA before and during fish-oil supplementation in healthy older individuals

Background: Docosahexaenoic acid (DHA) kinetics appear to change with intake, which is an effect that we studied in an older population by using uniformly carbon-13–labeled DHA (13C-DHA). Objective: We evaluated the influence of a fish-oil supplement over 5 mo on the kinetics of 13C-DHA in older persons. Design: Thirty-four healthy, cognitively normal participants (12 men, 22 women) aged between 52 and 90 y were recruited. Two identical kinetic studies were performed, each with the use of a single oral dose of 40 mg 13C-DHA. The first kinetic study was performed before participants started taking a 5-mo supplementation that provided 1.4 g DHA/d plus 1.8 g eicosapentaenoic acid (EPA)/d (baseline); the second study was performed during the final month of supplementation (supplement). In both kinetic studies, blood and breath samples were collected ≤8 h and weekly over 4 wk to analyze 13C enrichment. Results: The time × supplement interaction for 13C-DHA in the plasma was not significant, but there were separate time and supplement effects (P < 0.0001). The area under the curve for plasma 13C-DHA was 60% lower while subjects were taking the supplement than at baseline (P < 0.0001). The uniformly carbon-13–labeled EPA concentration was 2.6 times as high 1 d posttracer while patients were taking the supplement as it was at baseline. The mean (±SEM) plasma 13C-DHA half-life was 4.5 ± 0.4 d at baseline compared with 3.0 ± 0.2 d while taking the supplement (P < 0.0001). Compared with baseline, the mean whole-body half-life was 61% lower while subjects were taking the supplement. The loss of 13C-DHA through β-oxidation to carbon dioxide labeled with carbon-13 increased from 0.085% of dose/h at baseline to 0.208% of dose/h while subjects were taking the supplement. Conclusions: In older persons, a supplement of 3.2 g EPA + DHA/d increased β-oxidation of 13C-DHA and shortened the plasma 13C-DHA half-life. Therefore, when circulating concentrations of EPA and DHA are increased, more DHA is available for β-oxidation. This trial was registered at clinicaltrials.gov as NCT01577004

Being punk in higher education: subcultural strategies for academic practice

Since its beginnings in the late 1970s, punk culture has been associated with counter-mainstream ideology and anti-institutional antagonism. In particular, formal education has been criticised in punk for sustaining oppressive social and conceptual orders and associated behavioural norms. Drawing on literature and interviews, this paper focuses on the experiences of higher education teachers who self-identify as punks, and considers how they negotiate and reconcile their subcultural and academic identities in their academic practice. The findings reveal that participants’ affiliations with punk subculture give rise to counter-cultural pedagogies in which both the ethics and aesthetics of punk are applied in classroom contexts. Furthermore, the participants draw upon subcultural ethical and epistemological narratives to formulate and rationalise their responses to the state of contemporary UK higher education

European Food Safety Authority; Outcome of the Public consultation on the Draft Opinion of the Scientific Panel on Dietetic products, Nutrition, and Allergies (NDA) on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol

On 2 July 2009, the EFSA Panel on Dietetic products, Nutrition and Allergies (NDA) endorsed a draft Opinion on Dietary Reference Values for fats to be released for public consultation. This Scientific Report summarises the comments received through the public consultation and outlines how these were taken into account in the final opinion. EFSA had received contributions from 40 interested parties (individuals, non-governmental organisations, industry organisations, academia and national assessment bodies). The main comments which were received during the public consultation related to: the availability of more recent data, the nomenclature used, the use of a non-European food composition data base, the impact of genetic factors in modulating the absorption, metabolism and health effects of different fatty acids, the definition of “nutritionally adequate diet”, the use of Dietary Reference Values in the labelling of foods, the translation of advice into food-based dietary guidelines, nutrient goals and recommendations, certain risk management issues, and to Dietary Reference Values of fats, individual fatty acids, and cholesterol. All the public comments received that related to the remit of EFSA were assessed and the Opinion on Dietary Reference Values for fats has been revised taking relevant comments into consideration