Friends and Family: How African-American Adolescents' Perceptions of Dietary Beliefs and Behaviors of Others Relate to Diet Quality.

BACKGROUND: Adolescents' dietary intake often fails to meet national dietary guidelines, especially among low-income African-American youth. The dietary habits established in adolescence are likely to continue into adulthood, and a poor-quality diet increases the risk of developing obesity and chronic disease. Based on principles from ecological and social-cognitive behavior change health theories, perceptions of parental beliefs about healthy eating, perceptions of peer eating behaviors, and parental monitoring of what adolescents eat may positively influence adolescent diet quality. OBJECTIVE: The purposes of this study were to determine whether perceived parental beliefs about nutrition, perceived peer eating behaviors, and reported parental monitoring of the adolescent diet were related to African-American adolescent diet quality and whether these relationships were moderated by adolescent age or sex. DESIGN: This secondary cross-sectional study used baseline data (2002 to 2004) from an urban community sample of low-income adolescents participating in a health promotion trial. PARTICIPANTS/SETTING: Participants were 216 African-American adolescent-caregiver dyads in Baltimore, MD. MAIN OUTCOME MEASURES: The 2010 Healthy Eating Index was used to estimate adolescent diet quality. STATISTICAL ANALYSES PERFORMED: Analyses included correlations, t tests, age- and sex-by-perception regression interactions, and multivariate regressions adjusted for body mass index-for-age percentile, caregiver weight status, and caregiver depressive symptoms. RESULTS: Higher diet quality scores were related to higher levels of perceived parental and peer support for healthy eating behaviors among adolescents (ß=.21; P<0.05; ß=.15; P<0.05, respectively) and to caregiver reports of parental monitoring of adolescent dietary behavior (ß=1.38, P<0.01). Findings were not moderated by age or sex. CONCLUSIONS: Consistent with ecological and social-cognitive theories, adolescents look to their friends and family in making healthy food choices. The relationships uncovered by this study describe some of the contextual, interpersonal influences associated with diet quality among low-income, urban African-American adolescents and warrant further exploration in future intervention studies.

Comparison of the HEI and HEI-2010 Diet Quality Measures in Association with Chronic Disease Risk among Low-Income, African American Urban Youth in Baltimore, Maryland.

OBJECTIVE: Overall diet patterns may be a better predictor of disease risk than specific nutrients or individual foods. The purpose of this study is to examine how overall diet patterns relate to nutritional intake, body composition, and physiological measures of chronic disease risk among low-income, urban African American adolescents. METHODS: Cross-sectional data were collected from two samples of African American adolescents (n = 317) from a low-income urban community, including dietary intake using the food frequency Youth/Adolescent Questionnaire and anthropometric measures. Serum cholesterol, serum lipoproteins, and glucose tolerance were measured in a subsample. Means testing compared differences in Healthy Eating Index (HEI) and Healthy Eating Index-2010 (HEI-2010) component and total scores. Pearson correlations examined how HEI and HEI-2010 scores related to nutrient, food intakes, and markers of disease risk, including body mass index, percent body fat, abdominal fat, serum cholesterol, serum lipoproteins, and impaired glucose tolerance. Fisher R-Z transformations compared magnitude differences between HEI and HEI-2010 correlations to nutritional intake and chronic disease risk. RESULTS: Both HEI and HEI-2010 scores were positively associated with micronutrient intakes. Higher HEI scores were inversely related to serum cholesterol, low-density lipoprotein, impaired glucose tolerance, percent body fat, and percent abdominal fat. HEI-2010 scores were not related to biomarkers of chronic disease risk. CONCLUSIONS: Compared to the HEI-2010, the HEI is a better indicator of chronic disease risk among low-income, urban African American adolescents.

Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging.

BACKGROUND: Caloric restriction (CR) can increase longevity in rodents and improve memory function in humans. α-Lipoic acid (LA) has been shown to improve memory function in rats, but not longevity. While studies have looked at survival in rodents after switching from one diet to another, the underlying mechanisms of the beneficial effects of CR and LA supplementation are unknown. Here, we use RNA-seq in cerebral cortex from rats subjected to CR and LA-supplemented rats to understand how changes in diet can affect aging, neurodegeneration and longevity. RESULTS: Gene expression changes during aging in ad libitum-fed rats are largely prevented by CR, and neuroprotective genes are overexpressed in response to both CR and LA diets with a strong overlap of differentially expressed genes between the two diets. Moreover, a number of genes are differentially expressed specifically in rat cohorts exhibiting diet-induced life extension. Finally, we observe that LA supplementation inhibits histone deacetylase (HDAC) protein activity in vitro in rat astrocytes. We find a single microRNA, miR-98-3p, that is overexpressed during CR feeding and LA dietary supplementation; this microRNA alters HDAC and histone acetyltransferase (HAT) activity, which suggests a role for HAT/HDAC homeostasis in neuroprotection. CONCLUSIONS: This study presents extensive data on the effects of diet and aging on the cerebral cortex transcriptome, and also emphasises the importance of epigenetics and post-translational modifications in longevity and neuroprotection.

Symptom-Onset Dosing of Sertraline for the Treatment of Premenstrual Dysphoric Disorder: A Randomized Clinical Trial.

IMPORTANCE: Serotonin reuptake inhibitors (SRIs) are efficacious treatments for premenstrual dysphoric disorder (PMDD) when given daily or for half of the menstrual cycle during the luteal phase. Preliminary studies suggest that SRI treatment can be shortened to the interval from symptom onset through the beginning of menses. OBJECTIVE: To determine the efficacy of symptom-onset dosing with the SRI sertraline hydrochloride for treatment of PMDD. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled, multisite, parallel-group randomized clinical trial conducted September 1, 2007, to February 29, 2012, at 3 university medical centers. In all, 252 women with PMDD started treatment at symptom onset and continued until the first few days of menses for 6 menstrual cycles. Intent-to-treat analyses were performed February 28, 2014, through April 21, 2015. INTERVENTIONS: Placebo or sertraline hydrochloride, 50 to 100 mg/d, during the symptomatic interval. MAIN OUTCOMES AND MEASURES: Premenstrual Tension Scale (PMTS) score was the primary outcome measure (score range, 0-36; 36 indicates most severe score). Secondary outcome measures included the Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C) (score range, 0-84; 84 indicates most severe score), Daily Record of Severity of Problems (DRSP) (total and subscale scores; higher scores indicate most severe problems), Clinical Global Impression (CGI) scales (score range, 1-7; 7 indicates most severe symptoms and least improvement), and Michelson SSRI (Selective SRI) Withdrawal Symptoms Scale scores (range, 0-51; higher scores indicate more severe withdrawal symptoms). RESULTS: Among the participants, 125 with PMDD were randomized to sertraline, and 127 to placebo. At baseline the mean (SD) PMTS scores for sertaline and placebo were 22.3 (4.8) and 21.4 (4.5), respectively, which declined to 11.7 (6.8) and 12.0 (6.9), respectively; group mean difference, 1.88 (95% CI, 0.01-3.75; P = .06). The mean (SD) estimated difference in IDS-C scores between baseline (35.4 [10.7] for sertraline; 32.8 [10.4] for placebo) and the end point (15.3 [10.7] for sertraline; 17.8 [11.0] for placebo) favored the sertraline group by 5.14 (95% CI, 1.97-8.31) points (P = .02). Compared with the placebo group, those assigned to sertraline showed greater improvement on the total DRSP score (estimated mean difference, 1.09 [95% CI, 0.96-1.25] points; P = .02) and Anger/Irritability DRSP subscale score (1.22 [95% CI, 1.05-1.41] points; P < .01) and were more likely to respond to treatment (77 of 115 patients [67.0%] for sertraline and 65 of 124 [52.4%] for placebo; χ21 = 5.23; P = .02). The mean (SD) number of symptomatic days before treatment diminished over time (sertraline, -0.7 [3.4] days; placebo, -1.0 [3.2] days), with no group differences in symptomatic days or the Michelson SSRI Withdrawal Symptoms Scale. CONCLUSIONS AND RELEVANCE: Depending on the symptom scale, women with PMDD may or may not benefit from SRI treatment during the interval from the onset of premenstrual symptoms through the first few days of menses. Abrupt treatment cessation was not associated with discontinuation symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00536198.

Perinatal substance use: a prospective evaluation of abstinence and relapse.

BACKGROUND: Substance use decreases in pregnancy but little prospective data are available on the rates of abstinence and relapse for specific substances. This study compared rates of abstinence in pregnancy and relapse postpartum for nicotine cigarettes, alcohol, marijuana, and cocaine. METHODS: Data from 152 women drawn from a randomized controlled trial comparing psychological treatments for substance use in pregnancy were analyzed. Self-reports of substance use and urine for toxicology testing throughout pregnancy and 3-months, 12-months and 24-months post-delivery were collected. Multivariate Cox models were used to compare rates of abstinence and relapse across substances. RESULTS: In pregnancy, 83% of all women achieved abstinence to at least one substance. The mean (SE) days to abstinence was 145.81 (9.17), 132.01 (6.17), 151.52 (6.24), and 148.91 (7.68) for cigarettes, alcohol, marijuana and cocaine, respectively. Participants were more likely to achieve abstinence from alcohol (HR 7.24; 95% CI 4.47-11.72), marijuana (HR 4.06; 95% CI 1.87-6.22), and cocaine (HR 3.41; 95% CI 2.53-6.51), than cigarettes. Postpartum, 80% of women abstinent in the last month of pregnancy relapsed to at least one substance. The mean days to relapse was 109.67 (26.34), 127.73 (21.29), 138.35 (25.46), and 287.55 (95.85) for cigarettes, alcohol, marijuana and cocaine, respectively. Relapse to cocaine was only 34% (HR 0.34; 95% CI 0.15-0.77) that of cigarettes. CONCLUSIONS: Pregnancy-related abstinence rates were high for all substances except cigarettes. Postpartum relapse was common, with cocaine using women being less likely to relapse after attaining abstinence compared to women using cigarettes, alcohol or marijuana.

Maternal mental health and infant dietary patterns in a statewide sample of Maryland WIC participants.

The study's objective was to examine the relation between maternal mental health and infant dietary intake. A cross-sectional, population-based telephone survey was employed within a statewide sample of Maryland Special Supplemental Nutrition Program for Women, Infants and Children participants. A 24-h diet recall was performed using the United States Department of Agriculture Automated Multiple-Pass Method. Analyses presented were based on 689 mother-infant pairs. Overall, 36.5% of mothers reported introducing solids to their infants early (<4 months of age), and 40% reported adding cereal to their infant's bottle. Among 0-6-month-old infants, higher infant energy intake was associated with symptoms of maternal stress [ß=0.02; confidence interval (CI): 0.01, 0.04], depression (ß=0.04; CI: 0.01, 0.06) and overall maternal psychological distress (ß=0.02; CI: 0.003, 0.03). With early introduction of solids in the model, the significant associations between infant energy intake and maternal stress and maternal psychological distress became marginal (P's=0.06-0.10). The association between infant energy intake and maternal depression remained significant (ß=0.03; CI: 0.01, 0.06). Among 4-6-month-old infants, intakes of breads and cereals were higher among mothers who reported more symptoms of stress (ß=0.12; CI: 0.04, 0.23), depression (ß=0.19; CI: 0.03, 0.34), anxiety (ß=0.15; CI: 0.02, 0.27) and overall psychological distress (ß=0.04; CI: 0.01, 0.07). Among 7-12-month-old infants, dietary intake was not related to mental health symptoms. Findings suggest poorer infant feeding practices and higher infant dietary intake during the first 6 months of age in the context of maternal mental health symptoms. Further research is needed to evaluate these effects on child dietary habits and growth patterns over time.

Progesterone Reduces Cocaine Use in Postpartum Women with a Cocaine Use Disorder: A Randomized,Double-Blind Study.

BACKGROUND: Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD). METHODS: A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized to placeboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites. FINDINGS: Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ2 =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events. INTERPRETATION: These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through. FUNDING: US National Institute on Drug Abuse; Veterans Administration.

A-to-I RNA editing does not change with age in the healthy male rat brain.

RNA editing is a post-transcriptional process, which results in base substitution modifications to RNA. It is an important process in generating protein diversity through amino acid substitution and the modulation of splicing events. Previous studies have suggested a link between gene-specific reductions in adenosine to inosine RNA editing and aging in the human brain. Here we demonstrate that changes in RNA editing observed in humans with age are not observed during aging in healthy rats. Furthermore, we identify a conserved editing site in rats, in Cog3. We propose that either age-related changes in RNA editing are specific to primates or humans, or that they are the manifestation of disease pathology. Since rodents are often used as model organisms for studying aging, these findings demonstrate the importance of understanding species-specific differences in RNA biology during aging.

Whole transcriptome sequencing of the aging rat brain reveals dynamic RNA changes in the dark matter of the genome.

Brain aging frequently underlies cognitive decline and is a major risk factor for neurodegenerative conditions. The exact molecular mechanisms underlying brain aging, however, remain unknown. Whole transcriptome sequencing provides unparalleled depth and sensitivity in gene expression profiling. It also allows non-coding RNA and splice variant detection/comparison across phenotypes. Using RNA-seq to sequence the cerebral cortex transcriptome in 6-, 12- and 28-month-old rats, age-related changes were studied. Protein-coding genes related to MHC II presentation and serotonin biosynthesis were differentially expressed (DE) in aging. Relative to protein-coding genes, more non-coding genes were DE over the three age-groups. RNA-seq quantifies not only levels of whole genes but also of their individual transcripts. Over the three age-groups, 136 transcripts were DE, 37 of which were so-called dark matter transcripts that do not map to known exons. Fourteen of these transcripts were identified as novel putative long non-coding RNAs. Evidence of isoform switching and changes in usage were found. Promoter and coding sequence usage were also altered, hinting of possible changes to mitochondrial transport within neurons. Therefore, in addition to changes in the expression of protein-coding genes, changes in transcript expression, isoform usage, and non-coding RNAs occur with age. This study demonstrates dynamic changes in RNA with age at various genomic levels, which may reflect changes in regulation of transcriptional networks and provides non-coding RNA gene candidates for further studies.

Caloric restriction increases adiponectin expression by adipose tissue and prevents the inhibitory effect of insulin on circulating adiponectin in rats.

Aging is associated with redistribution of body fat and the development of insulin resistance. White adipose tissue emerges as an important organ in controlling life span. Caloric restriction (CR) delays the rate of aging possibly modulated partly by altering the amount and function of adipose tissue. Adiponectin is a major adipose-derived adipokine that has anti-inflammatory and insulin-sensitizing properties. This study examined the effects of CR on adiposity and gene expression of adiponectin, its receptors (AdipoR1 and AdipoR2) in adipose tissue and in isolated adipocytes of Brown Norway rats that had undergone CR for 4 months or fed ad libitum. The study also determined plasma concentrations of adiponectin and insulin in these animals and whether insulin infusion for 7 days affects adiponectin expression and its circulating concentrations under CR conditions. CR markedly reduced body weight as anticipated, epididymal fat mass and adipocyte size. CR led to an increase in plasma free fatty acid and glycerol (both twofold), and adipose triglyceride lipase messenger RNA (mRNA) in adipose tissue and isolated adipocytes (both >2-fold). Adiponectin mRNA levels were elevated in adipose tissue and adipocytes (both >2-fold) as was plasma adiponectin concentration (2.8-fold) in CR rats. However, CR did not alter tissue or cellular AdipoR1 and AdipoR2 expression. Seven days of insulin infusion decreased adiponectin mRNA in adipose tissue but did not reverse the CR-induced up-regulation of circulating adiponectin levels. Our results suggest that the benefits of CR could be, at least in part, dependent on enhanced expression and secretion of adiponectin by adipocytes.

Ethnic Group Differences in the Outcomes of Multidisciplinary Pain Treatment.

OBJECTIVES: The aim of this prospective investigation was to evaluate ethnic group differences in pain-related outcomes following multidisciplinary chronic pain treatment. A prospective pre- and post-treatment assessment design was employed to investigate the effects of ethnicity on changes in pain-related variables following completion of a multidisciplinary pain treatment program. METHODS: One hundred fifty five chronic pain patients participating in a multidisciplinary pain treatment program completed measures of pain and mood both prior to and following the four-week treatment. Primary outcome variables included pain severity, pain-related interference, and depressive symptoms. RESULTS: Baseline differences between African-Americans and Whites were observed for depressive symptoms, but not for pain severity or pain-related interference. Following multidisciplinary pain treatment, both White and African-American patients displayed post-treatment reductions in depressive symptoms and pain-related interference. However, White patients also reported reduced pain severity while African-Americans did not. CONCLUSIONS: The treatment approach used in the present study appeared to be less effective in reducing self-reported pain severity in African-American versus White patients, though both groups benefited in terms of reduced depressive symptoms and pain-related interference. Moreover, the observation that improvements in functioning occurred without reductions in pain severity in African-American patients suggests that differences may exist in treatment processes as a function of ethnic group, and will consequently be an important area for future research.

Whole-genome microarray analysis identifies up-regulation of Nr4a nuclear receptors in muscle and liver from diet-restricted rats.

One of the most conserved methods to significantly increase lifespan in animals is through dietary restriction (DR). The mechanisms by which DR increases survival are controversial but are thought to include improvements in mitochondrial function concomitant with reductions in reactive oxygen species production and alterations in the insulin signalling pathway, resulting in global metabolic adaptation. In order to identify novel genes that may be important for lifespan extension of Brown Norway rats, we compared gene expression profiles from skeletal muscle of 28-month-old animals fed ad libitum or DR diets using whole-genome arrays. Following DR, 426 transcripts were significantly down-regulated whilst only 52 were up-regulated. Included in the up-regulated transcripts were three functionally related previously unidentified DR-regulated genes: Nr4a1, Nr4a2, and Nr4a3. Up-regulation of all three Nr4a receptors was also observed in liver - but not brain - of DR-fed animals. Furthermore, RT-PCR revealed up-regulation of several NR4A transcriptional targets (Ucp-3, Ampk-gamma3, Pgc-1alpha and Pgc-1beta) in skeletal muscle of DR animals. Due to the proposed roles of the NR4A nuclear receptors in sensing and responding to changes in the nutritional environment and in regulating glucose and lipid metabolism and insulin sensitivity, we hypothesise that these proteins may contribute to DR-induced metabolic adaptation.

The healthy eating index and youth healthy eating index are unique, nonredundant measures of diet quality among low-income, African American adolescents.

Chronic disease is related to poor diet quality. The Healthy Eating Index (HEI) was developed to assess diet quality. The Youth HEI (YHEI) is an adaptation of the HEI for use with children and adolescents. The objectives were to compare HEI and YHEI scores among adolescents at risk for chronic disease and to compare associations between the scores and health indicators. This cross-sectional study included 2 low-income, urban African American adolescent samples (Challenge, n = 196; Three Generation, n = 121). HEI and YHEI scores were calculated from a FFQ and compared with BMI, body composition, and micronutrient, energy, and dietary intakes. YHEI scores were lower than HEI scores across both adolescent samples (Challenge, 48.94 +/- 9.31 vs. 62.83 +/- 11.75; Three Generation, 47.08 +/- 9.65 vs. 59.93 +/- 11.27; P < 0.001). Females (64.47 +/- 11.70) had higher HEI scores than males (61.15 +/- 11.61) (P < 0.05), but there was no gender difference in YHEI scores. HEI and YHEI scores were associated with higher micronutrient and total energy intakes (r = 0.19-0.76; P < 0.05). Higher percent body/abdominal fat was associated with lower HEI scores (r = -0.17 to -0.19; P < 0.05) but not with YHEI scores. BMI was not associated with either HEI or YHEI scores. In conclusion, many adolescents were consuming diets that placed them at risk for developing chronic disease. Although both the HEI and YHEI are useful in assessing diet quality, the HEI is inversely associated with body composition, a predictor of chronic disease, and accounts for gender differences in the Dietary Guidelines, whereas the YHEI discounts nutrient-poor, energy-dense foods.

Seasons of survivorship revisited.

Several decades ago the chance of a cancer survivor enjoying long-term survival was limited. At that time the terms cancer survivor and cancer survivorship were new. A cancer survivor was defined as a person from the moment of diagnosis onward for as long as they live. Cancer survivorship was also described in several "seasons" including; acute survivorship (the experience of diagnosis and treatment), extended survivorship (a time for "watchful waiting"), and then permanent survivorship (long-term remission). Today, acute cancer survivorship is still a time of intense emotion and medical activity surrounding the diagnosis, staging, and actual treatment. We then propose that after the intense initial therapy is completed the survivors enter a "season" that can be called "transitional cancer survivorship" reflecting the transition from active treatment to careful observation and the emotional, social, and medical adaptations that occur. Next, there are a growing number of cancer survivors who are (1) alive and "living with cancer" but requiring ongoing treatment for recurrent, active, and often advanced disease; (2) in a complete remission that requires ongoing therapy; or (3) in a complete remission and with a favorable prognosis. Collectively, this is a diverse group in "extended survivorship" and some later go on to obtain a permanent remission although others experience disease progression. Finally, there are millions of long-term or "permanent survivors." This group is also very heterogeneous and is comprised of 4 subgroups including (1) survivors who are "cancer-free but not free of cancer," (2) survivors who are cancer-free but continue to have significant "fall-out" from cancer and its treatment including psychosocial, medical, financial, or legal sequelae, (3) survivors who go on to develop second cancers which may be unrelated to the first cancer or its treatment, or may be more likely due to genetic or environmental factors, and also (4) survivors who later develop cancers that are secondary to the initial treatment.

Dietary lipoic acid supplementation can mimic or block the effect of dietary restriction on life span.

Dietary restriction feeding extends survival in a range of species but a detailed understanding of the underlying mechanism is lacking. There is interest therefore in identifying a more targeted approach to replicate this effect on survival. We report that in rats dietary supplementation with alpha-lipoic acid, has markedly differing effects on lifetime survival depending upon the dietary history of the animal. When animals are switched from DR feeding to ad libitum feeding with a diet supplemented with alpha-lipoic acid, the extended survival characteristic of DR feeding is maintained, even though the animals show accelerated growth. Conversely, switching from ad libitum feeding a diet supplemented with alpha-lipoic acid to DR feeding of the non-supplemented diet, blocks the normal effect of DR to extend survival, even after cessation of lipoic acid supplementation. Unlike the dynamic effect of switching between DR and ad libitum feeding with a non-supplemented diet where the subsequent survival trajectory is determined by the new feeding regime, lipoic acid fixes the survival trajectory to that established by the initial feeding regime. Ad libitum feeding a diet supplemented with lipoic acid can therefore act as mimetic of DR to extend survival.

Lack of effect of caloric restriction on bioenergetics and reactive oxygen species production in intact rat hepatocytes.

To investigate the hypothesis that caloric restriction alters mitochondrial function in situ, intact hepatocytes were isolated from fully fed and calorie-restricted (55% of control food intake, 4 months duration) male Brown-Norway rats at 6 months of age, and various parameters were determined. Overall, the production of reactive oxygen species was not affected by caloric restriction, neither were the mitochondrial membrane potential, oxygen consumption driving proton leak, or oxygen consumption driving ATP turnover. It is concluded that while isolated mitochondria from liver tissue of calorie-restricted animals display a reduction in the generation of reactive oxygen species, it was not possible to confirm this effect in isolated hepatocytes. Further work is required to establish what effect, if any, caloric restriction has on the rate of generation of reactive oxygen species in intact cells and tissues and importantly at the whole-animal level.

Effect of ageing and caloric restriction on specific markers of protein oxidative damage and membrane peroxidizability in rat liver mitochondria.

To gain insight into the anti-ageing mechanisms of caloric restriction (CR), liver mitochondria were isolated from male Brown-Norway rats of different ages (fully fed control and CR) and various specific markers of non-enzymatic protein modification (by oxidative, glyco- and lipoxidative-reactions) were measured by GC/MS and Western blotting. A membrane peroxidizability index (PI) was calculated from the fatty acid profiles. Between 6 and 18 months of age, there were significant decreases in the concentration of all markers of damage in mitochondria from both the fully fed and CR groups. In contrast, between the ages of 18 and 28 months, there were significant increases in the concentrations of all markers of damage. In mitochondria from both fully fed and CR groups, there were significant increases in N-epsilon (Nepsilon)-(carboxymethyl)lysine (CML) and N-epsilon-(malondialdehyde)lysine (MDAL) between 6 and 28 months of age. In general, damage tended to be lower in mitochondria from CR animals, but the effects were not significant, except for the concentration of N-epsilon-(carboxymethyl)lysine at 28 months of age. PI increased steadily and significantly with age in fully fed animals, whilst CR induced a significant decrease in this index at 28 months of age. It is concluded that for male rats of the Brown-Norway strain, and mitochondria from liver (i) old (but not mature) age is associated with an increased membrane PI and protein oxidative damage and (ii) CR does not lead to a general reversion in age-related protein damage, but it does prevent the age-induced increase in PI very late in life.

Exogenous insulin can reverse the effects of caloric restriction on mitochondria.

It has been proposed that part of the anti-aging mechanism of caloric restriction (CR) involves a reduction in both the generation rate of reactive oxygen species (ROS) by mitochondria, and a reduction in peroxidizability of mitochondrial membranes. It was hypothesized that these effects may be due to upstream changes in hormonal status, since certain hormones (such as insulin) are stimulatory for ROS production, effect fatty acid composition, and are lowered by CR. To investigate this hypothesis, young male Brown-Norway rats on 55% CR (4 months duration) were subjected to insulin replacement by use of mini-osmotic pumps. ROS and free radical-induced malondialdehdye production were significantly lower in mitochondria from CR animals compared to those from fully fed, and these effects were reversed by insulin. It is concluded that the beneficial changes induced by CR, as seen at the mitochondrion, may in part be downstream effects of alterations in hormonal signalling.