Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid

An extensive body of evidence indicates that oxidative stress and inflammation play a central role in the degenerative changes of systemic tissues in aging. However a comparatively limited amount of data is available to verify whether these processes also contribute to normal aging within the brain. High levels of oxidative damage results in key cellular changes including a reduction in available nicotinamide adenine dinucleotide (NAD+), an essential molecule required for a number of vital cellular processes including DNA repair, immune signaling and epigenetic processing. In this study we quantified changes in [NAD(H)] and markers of inflammation and oxidative damage (F2-isoprostanes, 8-OHdG, total antioxidant capacity) in the cerebrospinal fluid (CSF) of healthy humans across a wide age range (24–91 years). CSF was collected from consenting patients who required a spinal tap for the administration of anesthetic. CSF of participants aged .45 years was found to contain increased levels of lipid peroxidation (F2-isoprostanes) (p = 0.04) and inflammation (IL-6) (p = 0.00) and decreased levels of both total antioxidant capacity (p = 0.00) and NAD(H) (p = 0.05), compared to their younger counterparts. A positive association was also observed between plasma [NAD(H)] and CSF NAD(H) levels (p = 0.03). Furtheranalysis of the data identified a relationship between alcohol intake and CSF [NAD(H)] and markers of inflammation. The CSF of participants who consumed .1 standard drink of alcohol per day contained lower levels of NAD(H) compared to those who consumed no alcohol (p,0.05). An increase in CSF IL-6 was observed in participants who reported drinking .0–1 (p,0.05) and .1 (p,0.05) standard alcoholic drinks per day compared to those who did not drink alcohol. Taken together these data suggest a progressive age associated increase in oxidative damage, inflammation and reduced [NAD(H)] in the brain which may be exacerbated by alcohol intake

The Relative Value of Measures of Omega-3 Index, Perceived Stress, Cortisol and Sleep Time in Identifying Depression Among a Cohort of Australian Adolescents

Objective: To assess the relative prognostic value of 11 variables including, omega-3, perceived stress, cortisol and sleep duration, in predicting adolescent depression. Design, Setting and Participants: A cross-sectional study of 444 healthy adolescents aged 16-18 years, from 10 schools within the Northern Sydney and Central Coast regions of New South Wales, Australia. Participants provided blood and saliva samples and completed questionnaires. Statistical classification methods were used to model the relationships between the predictors and depression. Main Outcome Measures: relative predictive value of each variable in correctly classifying depression. Results: 6% of boys and 9% of girls were categorised as experiencing severe to extremely severe depression. 4% of boys and 10% of girls were categorised as experiencing severe to extremely severe stress. The mean AM:PM cortisol for boys, 22±101, was higher than that of girls, 11±10. The average omega-3 index for boys, 10.5±3.7, was also higher than that of girls, 7.7±2.6. The average sleep duration of 7.8±1.1 hrs showed no gender differences. The best classification model identified perceived stress as the most significant predictor of depression followed by BMI and omega-3 index. Cortisol ratio was a significant discriminator for boys but not girls. When stress was excluded, shorter sleep duration became a significant discriminator in both boys and girls with waist to hip ratio providing further discrimination in girls only. Conclusion: The strongest predictor of depression in adolescents was perceived stress followed by higher BMI and lower omega-3 levels. These findings provide a rational basis for establishing program priorities for the prevention and treatment of adolescent depression

Suboptimal Omega-3 Levels in Australian Adolescents

Design, Setting and Participants:A cross-sectional descriptive study of 251 apparently healthy adolescents (192 female, 59 male) aged 15-17 years, in year 11, from 10 schools within the Northern Sydney and Central Coast areas of New South Wales. Participants provided a morning non-fasting blood sample via finger-prick and written answers to specific demographic and lifestyle questions. Omega-3 index was calculated by adding %EPA and %DHA values in the whole blood. Equivalent erythrocyte omega-3 index values were obtained by using conversion factors (1.33 for EPA and 2.22 for DHA) from published erythrocyte/whole blood values. Main Outcome Measures: Quantitation of the individual, and estimation of the group average, blood omega-3 Index. Results:The blood omega-3 Index for this adolescent cohort ranged from 2.1-22.3 with a mean of 8.3±3.2, and median of 7.8. On average males had a higher omega-3 Index compared to females (10.5±3.7 vs 7.7±2.6, p8. Three percent had an Index of On average, adolescents from low or medium socioeconomic communities had a significantly lower omega-3 Index compared to those from higher socioeconomic neighbourhoods (mean difference=1.4, p=0.018). Overall 20% of boys and 17% of girls reported regularly taking omega-3 supplements. Regular use of omega-3 supplements was associated with a higher average omega-3 Index (9.8±3.7, n=44 compared to 8.0±3.0, n=203, p=0.001 in those not taking supplements). Conclusion:This study indicates that Australian adolescents, even when from advantaged homes, have a high probability of below optimum omega-3 levels. As reduced omega-3 levels are linked to conditions of public health concern such as diabetes, asthma and depression, targeted strategies to improve the omega-3 status in the childhood population may be warranted

Struggling to Stay Awake: The Sleep Patterns of Adventist Secondary School Students

Sleep deprivation studies indicate that sleep is vital to emotional, physical and behavioural wellbeing. This study presents the results of a survey in which 945 students in Seventh-day Adventist secondary schools responded to questions about the length and quality of their sleep. The study found that: almost one half of the students were at risk of falling short of the recommended number of hours of sleep per night; toward one in every five students were averaging six or fewer hours sleep per night; the quality of sleep (in terms of better sleep habits) and the resulting levels of daytime alertness were clearly linked to having a permanent, personal space for sleep; and finally that academic performance was strongly related to measures of daytime alertness and measures of the quality of sleep habits

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of deat

Open Access

Cerebrospinal fluid levels of inflammation, oxidative stress and NAD + are linked to differences in plasma carotenoid concentration

Oxidative damage and inflammation in the central nervous system: influence of age and specific nutritional elements

The studies presented in this thesis were designed to quantitate and compare the influence of age and selected dietary elements on oxidative and inflammatory activity and circulating levels of the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+), in the human systemic circulation and central nervous system (CNS). The data presented shows significant associations between aging and a progressive increase in oxidative and inflammatory processes concomitant with a reduction in NAD+ availability both systemically and within the CNS, even in the absence of disease. Evidence is further provided indicating that these biochemical changes may be exacerbated by consumption of alcohol or foods high in animal derived saturated fat and refined carbohydrates. Carotenoids, cobalamin (vitamin B12) and folate were also found to effect NAD+ levels and modulate oxidative and inflammatory processes. Considered together the evidence presented in this thesis suggests that oxidative and inflammatory activity, processes associated with aging and degenerative disease, can be influenced by dietary choices and that nutritional intervention may confer protection against age-related deficits, particularly in the central nervous system

Relationship between central and peripheral fatty acids in humans

Background: In recent years the physiological and pathological importance of fatty acids in both the periphery and central nervous system (CNS) has become increasingly apparent. However surprisingly limited research has been conducted comparing the fatty acid composition of central and peripheral lipid stores. Methods: The present study compared the distribution of polyunsaturated (PUFA), as well as specific saturated (SFA) and monounsaturated (MUFA) fatty acids in the whole blood and cerebrospinal fluid (CSF) of humans. Gas chromatography with flame ionization detection was used to determine the fatty acid profiles of twenty-eight matched CSF and whole blood samples. Multiple linear regression modeling, controlling for age, was used to identify significant relationships. Results: A significant positive relationship was seen between whole blood total omega-3 fatty acids and the CSF omega-3 subfractions, docosapentaenoic acid (DPA) (P = 0.019) and docosahexaenoic acid (DHA) (P = 0.015). A direct association was also observed between the whole blood and CSF omega-6 PUFA, arachidonic acid (AA) (P = 0.045). Interestingly an inverse association between central and peripheral oleic acid was also found (P = 0.045). Conclusions: These findings indicate a relationship between central and peripheral fatty acids of varying degrees of unsaturation and chain length and support the view that some systemic fatty acids are likely to cross the human blood brain barrier (BBB) and thereby influence central fatty acid concentrations

Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM) for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose) polymer production. Significant decreases in total NAD(H) and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM) decreased levels of NAD(H) in primary human astrocytes. NAD(H) depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H)]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene