Life Extension Magazine

Life Extension Magazine October 2010


Calorie Restriction

Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding.

Reduced cell proliferation may mediate anticarcinogenic effects of caloric restriction (CR). Using heavy water (2H2O) labeling, we investigated the cell proliferation response to CR in detail, including time course, effect of refeeding, and role of intermittent feeding with 5% CR. In the time-course study, 8-wk-old female C57BL/6J mice were placed on a 33% CR regimen (fed 3 times/wk) for varying durations. Compared with responses in controls fed ad libitum (AL), proliferation rates of keratinocytes, mammary epithelial cells, and T cells were markedly reduced within 2 wk of CR. In mice fed 95% ad libitum (C95, fed 3 times/wk), cell proliferation was also reduced in all tissues so that differences from 33% CR were only significant at 1 mo. In the refeeding study, mice were refed a C95 diet for varying durations after 1 mo of 33% CR. Cell proliferation rebounded to a suprabasal rate in all tissues after 2 wk of refeeding and then normalized after 2 mo, although the C95 group again exhibited lower cell proliferation than the AL group. The role of intermittent feeding was studied by comparing 33% CR and C95 animals (both fed intermittently) with animals fed isocalorically either daily or continuously by pellet dispenser. Intermittent feeding had no additive effect on 33% CR but reduced cell proliferation in all tissues at the 95% caloric intake level. In summary, the CR effect on cell proliferation is potent, rapid, and reversible in several tissues, and an intermittent feeding pattern reproduces much of the effect in the absence of substantial CR.

Am J Physiol Endocrinol Metab. 2005 May;288(5):E965-72

Emotional influences on food choice: sensory, physiological and psychological pathways.

Sensory, physiological and psychological mechanisms are reviewed that underlie emotional influences on food choice. Both moods and emotions are considered. Eating a meal will reliably alter mood and emotional predisposition, typically reducing arousal and irritability, and increasing calmness and positive affect. However, this depends on the meal size and composition being close to the eater’s habit, expectations and needs. Unusual meals--e.g. too small, unhealthy--may negatively affect mood. Sweetness, and sensory cues to high energy density, such as fatty texture, can improve mood and mitigate effects of stress via brain opioidergic and dopaminergic neurotransmission. However, adaptation in these pathways, perhaps enhanced by inherited sensitivity, with chronic exposure to such sensory qualities, could lead to overeating of energy-dense foods and consequent obesity. Sweet, fatty foods low in protein may also provide alleviation from stress in vulnerable people via enhanced function of the serotonergic system. Moreover, in rats, such foods seem to act as part of a feedback loop, via release of glucocorticoid hormones and insulin, to restrain activity of the hypothalamic pituitary adrenal axis during stress. However, this effect is also associated with abdominal obesity. In humans, a number of psychological characteristics predict the tendency to choose such foods when stressed, such as restrained or emotional eating, neuroticism, depression and premenstrual dysphoria, all of which could indicate neurophysiological sensitivity to reinforcing effects of such foods. Greater understanding of such predictive traits and the underlying mechanisms could lead to tailoring of diet to meet personal emotional needs.

Physiol Behav. 2006 Aug 30;89(1):53-61

The relationships among self-esteem, stress, coping, eating behavior, and depressive mood in adolescents.

The prevalence of adolescent overweight is significant, almost 25% in some minorities, and often is associated with depressive symptoms. Psychological and psychosocial factors as well as poor coping skills have been correlated with unhealthy eating and obesity. The purpose of this study was to examine relationships among self-esteem, stress, social support, and coping; and to test a model of their effects on eating behavior and depressive mood in a sample of 102 high school students (87% minority). Results indicate that (a) stress and low self-esteem were related to avoidant coping and depressive mood, and that (b) low self-esteem and avoidant coping were related to unhealthy eating behavior. Results suggest that teaching adolescents skills to reduce stress, build self-esteem, and use more positive approaches to coping may prevent unhealthy eating and subsequent obesity, and lower risk of depressive symptoms.

Res Nurs Health. 2009 Feb;32(1):96-109

Brain serotonin content: physiological regulation by plasma neutral amino acids.

When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.

Science. 1972 Oct 27;178(59):414-6

The composition of lunch determines afternoon plasma tryptophan ratios in humans.

It is well established that the ratio of the plasma tryptophan concentration to those of the other large neutral amino acids determines the transport of tryptophan into the brain. Brain tryptophan levels, in turn, control production of the neurotransmitter serotonin. Protein-rich meals, when consumed in the morning after an overnight fast, have been shown to decrease the plasma tryptophan ratio, while carbohydrate-rich meals have the opposite effect. We now show that these meals have similar effects when consumed for lunch, even if they are preceded by a small breakfast meal.

J Neural Transm. 1986;65(3-4):211-7

The treatment of obesity by carbohydrate deprivation suppresses plasma tryptophan and its ratio to other large neutral amino acids.

We measured plasma concentrations of tryptophan (Trp) and the other large neutral amino acids (LNAA) in 6 control and 7 obese subjects before and after they consumed a low-carbohydrate “protein-sparing modified fast” (PSMF) diet; LNAA levels in control subjects were also assessed after supplemental oral Trp. Consumption of the PSMF diet by non-obese subjects, or obesity per se, caused major reductions in the ratio of the plasma Trp concentration to the summed plasma concentrations of the other LNAA (i.e., the “plasma Trp ratio”), and may thus have diminished brain serotonin synthesis. Administration of even 2 g of supplemental Trp did not elevate the plasma Trp ratio beyond the normal range observed previously in subjects consuming carbohydrate-containing meals.

J Neural Transm. 1983;57(3):187-95

Chronic stress, combined with a high-fat/high-sugar diet, shifts sympathetic signaling toward neuropeptide Y and leads to obesity and the metabolic syndrome.

In response to stress, some people lose while others gain weight. This is believed to be due to either increased beta-adrenergic activation, the body’s main fat-burning mechanism, or increased intake of sugar- and fat-rich “comfort foods.” A high-fat, high-sugar (HFS) diet alone, however, cannot account for the epidemic of obesity, and chronic stress alone tends to lower adiposity in mice. Here we discuss how chronic stress, when combined with an HFS diet, leads to abdominal obesity by releasing a sympathetic neurotransmitter, neuropeptide Y (NPY), directly into the adipose tissue. In vitro, when “stressed” with dexamethasone, sympathetic neurons shift toward expressing more NPY, which stimulates endothelial cell (angiogenesis) and preadipocyte proliferation, differentiation, and lipid-filling (adipogenesis) by activating the same NPY-Y2 receptors (Y2Rs). In vivo, chronic stress, consisting of cold water or aggression in HFS-fed mice, stimulates the release of NPY and the expression of Y2Rs in visceral fat, increasing its growth by 50% in 2 weeks. After 3 months, this results in metabolic syndrome-like symptoms with abdominal obesity, inflammation, hyperlipidemia, hyperinsulinemia, glucose intolerance, hepatic steatosis, and hypertension. Remarkably, local intra-fat Y2R inhibition pharmacologically or via adenoviral Y2R knock-down reverses or prevents fat accumulation and metabolic complications. These studies demonstrated for the first time that chronic stress, via the NPY-Y2R pathway, amplifies and accelerates diet-induced obesity and the metabolic syndrome. Our findings also suggest the use of local administration of Y2R antagonists for treatment of obesity and NPY-Y2 agonists for fat augmentation in other clinical applications.

Ann N Y Acad Sci. 2008 Dec;1148:232-7

Asymmetric prefrontal cortex activation in relation to markers of overeating in obese humans.

Dietary restraint is heavily influenced by affect, which has been independently related to asymmetrical activation in the prefrontal cortex (prefrontal asymmetry) in electroencephalograph (EEG) studies. In normal weight individuals, dietary restraint has been related to prefrontal asymmetry; however, this relationship was not mediated by affect. This study was designed to test the hypotheses that, in an overweight and obese sample, dietary restraint as well as binge eating, disinhibition, hunger, and appetitive responsivity would be related to prefrontal asymmetry independent of affect at the time of assessment. Resting EEG recordings and self-report measures of overeating and affect were collected in 28 overweight and obese adults. Linear regression analyses were used to predict prefrontal asymmetry from appetitive measures while controlling for affect. Cognitive restraint and binge eating were not associated with prefrontal asymmetry. However, disinhibition, hunger, and appetitive responsivity predicted left-, greater than right-, sided prefrontal cortex activation independent of affect. Findings in this study add to a growing literature implicating the prefrontal cortex in the cognitive control of dietary intake. Further research to specify the precise role of prefrontal asymmetry in the motivation toward, and cessation of, feeding in obese individuals is encouraged.

Appetite. 2009 Aug;53(1):44-9

Long-term meditators self-induce high-amplitude gamma synchrony during mental practice.

Practitioners understand “meditation,” or mental training, to be a process of familiarization with one’s own mental life leading to long-lasting changes in cognition and emotion. Little is known about this process and its impact on the brain. Here we find that long-term Buddhist practitioners self-induce sustained electroencephalographic high-amplitude gamma-band oscillations and phase-synchrony during meditation. These electroencephalogram patterns differ from those of controls, in particular over lateral frontoparietal electrodes. In addition, the ratio of gamma-band activity (25-42 Hz) to slow oscillatory activity (4-13 Hz) is initially higher in the resting baseline before meditation for the practitioners than the controls over medial frontoparietal electrodes. This difference increases sharply during meditation over most of the scalp electrodes and remains higher than the initial baseline in the postmeditation baseline. These data suggest that mental training involves temporal integrative mechanisms and may induce short-term and long-term neural changes.

Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16369-73