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Biomedical subjects

S B Roberts

Publications and source records attributed to S B Roberts.

At least 91 records · Page 5Linked to original sources

Influence of age on energy requirements.

The effects of aging on energy requirements and energy expenditure were investigated in 35 healthy young men (mean +/- SE age, 22.7 +/- 0.6 y) and elderly men (68.0 +/- 1.5 y). Over a 10-d metabolic balance study, measurements were made of metabolizable energy intake for weight maintenance, total energy expenditure, resting energy expenditure, and thermic effect of feeding. Values for both metabolizable energy intake and total energy expenditure were significantly higher than the current recommended dietary allowance for energy in both age groups (P < 0.01). Total energy expenditures were 14.48 +/- 0.65 and 11.26 +/- 5.40 MJ/d in young and elderly men, respectively. The difference in total energy expenditure between the groups was accounted for by a significant decrease in all the major components of expenditure. These results suggest that the current recommended dietary allowances for energy may underestimate the usual energy needs of healthy adult men.

Adult↗

Effects of aging on energy requirements and the control of food intake in men.

Inadequate energy intake can be an important contributor to sarcopenia in older individuals, because negative energy balance induces negative nitrogen balance, independent of nitrogen intake. This review highlights recent studies from our laboratory on possible causes of negative energy balance in older individuals. Studies of energy requirements determined by measurement of total energy expenditure during weight maintenance, using the doubly labeled water technique, and the control of food intake following overeating and undereating indicate (a) that older individuals have higher energy requirements than anticipated, based on current Recommended Dietary Allowances for energy, and (b) that aging is associated with a significant impairment in the control of food intake, which inhibits appropriate compensation for prior changes in energy intake. The combination of unexpectedly high energy needs, and an inability to accurately control energy intake, increases the risk for negative energy balance and associated body fat and protein losses in older individuals.

Adult↗

The role of energy expenditure in energy regulation: findings from a decade of research.

The role of energy expenditure in energy regulation remains a subject of continuing controversy. New data have emerged from studies conducted over the last decade demonstrating that energy expenditure is a critical factor contributing to successful energy regulation in normal individuals, as well as to the disregulation of energy balance that characterizes obesity. Reduced energy expenditure appears to facilitate weight gain in individuals susceptible to obesity and also appears to reduce the extent of body energy loss during undereating in both lean and obese individuals. The magnitude of the reduction in energy expenditure during, and perhaps after, weight loss is greater than expected on the basis of the reduction in body weight and appears to occur in response to undefined underlying determinants of energy regulation. In addition, exercise intervention studies and cross-sectional investigations of the relationship between energy expenditure for physical activity and body composition demonstrate an apparent equilibration between physical activity and body fat content. This equilibration is suggestive of a direct influence of physical activity on the underlying metabolic determinants of energy balance.

Body Mass Index↗

Exercise training and nutritional supplementation for physical frailty in very elderly people.

BACKGROUND: Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied. METHODS: We conducted a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period. RESULTS: The mean (+/- SE) age of the 63 women and 37 men enrolled in the study was 87.1 +/- 0.6 years (range, 72 to 98); 94 percent of the subjects completed the study. Muscle strength increased by 113 +/- 8 percent in the subjects who underwent exercise training, as compared with 3 +/- 9 percent in the nonexercising subjects (P < 0.001). Gait velocity increased by 11.8 +/- 3.8 percent in the exercisers but declined by 1.0 +/- 3.8 percent in the nonexercisers (P = 0.02). Stair-climbing power also improved in the exercisers as compared with the nonexercisers (by 28.4 +/- 6.6 percent vs. 3.6 +/- 6.7 percent, P = 0.01), as did the level of spontaneous physical activity. Cross-sectional thigh-muscle area increased by 2.7 +/- 1.8 percent in the exercisers but declined by 1.8 +/- 2.0 percent in the nonexercisers (P = 0.11). The nutritional supplement had no effect on any primary outcome measure. Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation. CONCLUSIONS: High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people. In contrast, multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty.

Aged↗

Reversal of the Swedish familial Alzheimer's disease mutant phenotype in cultured cells treated with phorbol 12,13-dibutyrate.

Protein phosphorylation mediated by phorbol ester stimulates secretion of the beta-amyloid precursor protein (beta-APP) in the cell culture. This increase in secretion is produced by a transient increase in cleavage to produce non-amyloidogenic protease nexin II products mediated by the alpha-secretase activity, and a concomitant decrease in beta-protein production. Cells expressing the Swedish familial Alzheimer's disease (FAD) variant of beta-APP produce more beta-protein and potentially amyloidogenic fragments than cells expressing wild-type protein; furthermore, cleavage shifts from the alpha- to the beta-secretase cleavage site of the precursor. We show that treatment with phorbol 12,13-dibutyrate (PDBu) of cells expressing the Swedish FAD reverses the mutant phenotype to wild-type. The alpha-secretase cleavage increases with a concomitant loss of beta-protein and other beta-secretase cleaved products. These results show that modulating beta-secretase cleavage directly affects beta-protein production. It suggests that activating protein kinase C through, for example, muscarinic receptor agonists could reduce amyloidosis by modulating the level of beta-protein produced.

Alzheimer Disease↗

Non-amyloidogenic cleavage of the beta-amyloid precursor protein by an integral membrane metalloendopeptidase.

The beta-amyloid precursor protein (beta-APP) is a membrane spanning glycoprotein. The small beta-protein domain within the precursor is presumed to be the source of amyloid found in plaques characteristic of Alzheimer's disease. The amino terminus of beta-APP is released from cells by cleavages that produce both potentially amyloidogenic and nonamyloidogenic fragments of the carboxyl terminus. We developed a cell free system that imposes specificity and co-localization to characterize the proteolytic activity that cleaves the precursor within the beta-protein domain. A reporter protein containing the carboxyl-terminal 105 amino acids of beta-APP provided a specific substrate for cleavage at Lys16 of the beta-protein. The protease inhibitor profile and solubility characteristics of the activity demonstrate the cleavage is produced by an integral membrane metalloendopeptidase.

Alkaline Phosphatase↗

Altered cleavage and secretion of a recombinant beta-APP bearing the Swedish familial Alzheimer's disease mutation.

Mutations within the beta-amyloid precursor protein gene cosegregate with the early-onset form of familial Alzheimer's Disease (FAD). It is not known how these mutations result in disease; however, one early-onset AD mutation in a Swedish kindred increases potentially amyloidogenic fragments and beta-protein production in cells expressing the mutant beta-APP. Using a novel recombinant reporter system we found a qualitative change in the secreted product, from cleavage within the beta-protein sequence to cleavage near the N-terminal region of the beta-protein, even though the total amount of secreted mutant product is similar to wild-type. The results suggest that the increased formation of potentially amyloidogenic fragments in cells expressing the Swedish FAD occurs by enzymatic cleavage in the secretory pathway. Alterations in the secretory process may predispose an individual to AD.

Alzheimer Disease↗

Energy expenditure, aging and body composition.

We investigated the importance of adaptive variations in energy expenditure in the regulation of energy balance in young and elderly men of normal body weight leading unrestricted lives. Changes were measured in total and resting energy expenditure and body composition in response to overeating by approximately 4.2 MJ/d or undereating by 3.3 MJ/d for 21 d in 39 young and elderly men consuming a typical diet. In the young men, an average of 85-90% of the excess energy intake during overeating was deposited. During underfeeding, mobilization of body energy compensated for an average of 65% of the energy deficit in these subjects. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (+0.63 +/- 0.20 MJ/d, P < 0.01) and decreased during underfeeding (-0.42 +/- 0.12 MJ/d), but at least some of these changes were due to the obligatory expenditure associated with nutrient assimilation. There was no significant change in energy expenditure for physical activity or thermoregulation from overfeeding or underfeeding. Preliminary results indicate that aging had no effect on responses to overfeeding or underfeeding. These findings suggest that adaptive variations in energy expenditure are not the major determinant of energy regulation in young adults of normal body weight and that, instead, energy balance is maintained on a day-to-day basis through the control of nutrient intakes.

Adult↗

The Boston FICSIT study: the effects of resistance training and nutritional supplementation on physical frailty in the oldest old.

Research indicates that lower extremity muscle weakness in the elderly is consistently related to impaired mobility and fall risk. Reversible components of the muscle weakness of aging include underuse syndromes and undernutrition, both of which are prevalent in nursing home populations. The Boston FICSIT study is a nursing home-based intervention to improve muscle strength through progressive resistance training of the lower extremities and/or multi-nutrient supplementation in chronically institutionalized subjects aged 70-100. Baseline measurements of falls, medical status, psychological variables, functional status, nutritional intake and status, body composition, muscle mass and morphology, muscle function, and gait and balance are taken. The nursing home residents are then randomly assigned to one of four treatment groups for 10 weeks: (1) high intensity progressive resistance training of the hip and knee extensors 3 days per week; (2) multi-nutrient supplementation with a 360-kcal high carbohydrate, low fat liquid supplement every day; (3) a combination of groups (1) and (2); and (4) a control group. Both non-supplemented groups receive a liquid placebo every day, and both non-exercising groups attend three sessions of "leisure activities" every week in order to control for the attentional aspects of the exercise and nutritional interventions. At the end of the 10-week period, all baseline measurements are re-assessed.

Aged↗

Effect of fasting and feeding on measurement of carbon dioxide production using doubly labeled water.

The doubly labeled water method is a noninvasive technique for measurement of rates of CO2 production and total energy expenditure in free-living human subjects. The experimental protocol used in validation studies usually involves prolonged fasting before and after the isotope dose is given to start the study, although it is not clear whether this intrusive aspect of the method is necessary. We investigated this issue in four healthy adults [3 women and 1 man: age 29 +/- 2 (SD) yr, body mass index 22 +/- 2.7 kg.m2] with monitored constant physical activity who underwent two doubly labeled water studies that differed only in the duration of fasting before and after isotope dosing (either 6 h of fasting before and 5 h after dosing or 0.5 h before and 3 h afterward). No significant difference between the two measurements was found in the rate constants for isotope disappearance, the ratio of the dilution spaces of the isotopes, or CO2 production rate. These results indicate that prolonged fasting before and after isotope administration should not be necessary in doubly labeled water studies.

Adult↗

Underfeeding and body weight regulation in normal-weight young men.

The mechanisms of energy regulation invoked by moderate dietary restriction were investigated in seven healthy young men of normal body weight leading unrestricted lives. Following a baseline period of weight maintenance, subjects were underfed by 806 +/- 162 (mean +/- SE) kcal/day for 21 days. Changes in total energy expenditure (TEE) and resting energy expenditure (REE) and subsequent voluntary nutrient intakes were measured. The REE, averaged for fasting and fed states, decreased during underfeeding by 100 +/- 29 kcal/day (P less than 0.01). TEE decreased nonsignificantly by 296 +/- 170 kcal/day, equivalent to an average of 37% of the decrease in energy intake. Body energy stores were estimated to decrease by 510 +/- 172 kcal/day (P less than 0.03), thus compensating for 63% of the dietary energy deficit on average. Voluntary energy intake following dietary restriction increased above the initial amount required for body weight maintenance, was proportional to the weight loss during underfeeding (P less than 0.03), and was associated with a rapid regain of weight lost during underfeeding. These results indicate that energy balance is regulated by adaptive variations in both energy intake and energy expenditure in normal-weight young men leading unrestricted lives but do not support the hypothesis that energy-wasting mechanisms contribute substantially to body energy regulation.

Adult↗

What are the dietary energy needs of elderly adults?

The energy requirements of healthy elderly men were investigated by measuring total energy expenditure (TEE), body composition and resting energy expenditure (REE), using 2H2(18)O techniques and indirect calorimetry during ten days when a weight maintaining diet was consumed. Values for TEE/REE (1.75 +/- 0.05, s.e.) were significantly higher than the recommended dietary allowances (RDAs) for energy in this age group, as were previously reported values for TEE/REE in a group of young men in the same experimental protocol. There was a significant negative association between TEE/REE (a physical activity indicator) and body fat mass. Combining data from the elderly men in this study and the young men studied previously, age and TEE/REE together accounted for 73% of the variation in body fat mass between individuals. These results lend additional weight to the suggestion that the current RDAs for energy may significantly under-estimate usual energy requirements. They also indicate that the low levels of energy expenditure suggested by the RDAs may favour unnecessarily high levels of body fat mass and that increased levels of energy expenditure are desirable.

Adipose Tissue↗

Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity.

Oct-1 is a transcription factor involved in the cell cycle regulation of histone H2B gene transcription and in the transcription of other cellular housekeeping genes. Oct-1 is hyperphosphorylated as cells enter mitosis, and mitosis-specific phosphorylation is reversed as cells exit mitosis. A mitosis-specific phosphorylation site in the homeodomain of Oct-1 was phosphorylated in vitro by protein kinase A. Phosphorylation of this site correlated with inhibition of Oct-1 DNA binding activity in vivo and in vitro. The inhibition of Oct-1 DNA binding during mitosis suggests a mechanism by which the general inhibition of transcription during mitosis might occur.

Amino Acid Sequence↗

Differential phosphorylation of the transcription factor Oct1 during the cell cycle.

Orderly progression through the somatic cell division cycle is accompanied by phase-specific transcription of a variety of different genes. During S phase, transcription of mammalian histone H2B genes requires a specific promoter element and its cognate transcription factor Oct1 (OTF1). A possible mechanism for regulating histone H2B transcription during the cell cycle is direct modulation of Oct1 activity by phase-specific posttranslational modifications. Analysis of Oct1 during progression through the cell cycle revealed a complex temporal program of phosphorylation. A p34cdc2-related protein kinase that is active during mitosis may be responsible for one mitotic phosphorylation of Oct1. However, the temporally controlled appearance of Oct1 phosphopeptides suggests the involvement of multiple kinases and phosphatases. These results support the idea that cell cycle-regulated transcription factors may be direct substrates for phase-specific regulatory enzymes.

CDC2 Protein Kinase↗

DLW: a computer program for the calculation of total energy expenditure in doubly labeled water (2H218O) studies.

The double labeled water technique for determination of the rate of total energy expenditure in human subjects is based on measurement of the differential rates of disappearance of 2H and 18O from body water following oral administration of 2H218O. Two calculation procedures, the "two-point" and "slope-intercept" methods of calculation have previously been validated for use in humans. We describe here a computer program. DLW, that provides options to calculate doubly labeled water data in each of these accepted ways.

Adult↗

Dietary energy requirements of young adult men, determined by using the doubly labeled water method.

We examined the hypothesis that current recommendations on dietary energy requirements may underestimate the total energy needs of young adult men, by measuring total energy expenditure (TEE) and resting energy expenditure (REE) in 14 weight-maintaining healthy subjects leading unrestricted lives. TEE and body composition were measured by using 2H(2)18O, and REE was measured by using indirect calorimetry. All subjects had sedentary full-time occupations and participated in strenuous leisure activities for 34 +/- 6 (SE) min/d. TEE and REE were 14.61 +/- 0.76 and 7.39 +/- 0.26 MJ/d, respectively, and 202 +/- 2 and 122 +/- 2 kJ.kg-1.d-1. There were significant relationships between TEE and both body fat-free mass (r = 0.732, P less than 0.005) and measured REE (r = 0.568, P less than 0.05). Measured TEE:REE values were significantly higher than the recommended energy requirement (1.98 +/- 0.09, compared with 1.55 or 1.67, P less than 0.005). These results are consistent with the suggestion that the current recommended energy intake for young adult men may underestimate total energy needs.

Adult↗

Objective verification of dietary intake by measurement of urine osmolality.

A new method for assessing the accuracy of dietary nutrient intakes in metabolic studies is described. The theoretical basis of the method is the comparison of measurements of the urine osmole excretion rate (OER, the product of urine osmolality and urine weight) with values for OER predicted from dietary nitrogen, sodium, and potassium. The method was tested in 34 healthy male and female volunteers aged 18-78 y who made complete 24-h urine collections and consumed a diet over 6 d in metabolic-balance studies involving either overfeeding, weight maintenance, or weight loss. The coefficients of variation for equations relating measured OER to dietary nitrogen, sodium, and potassium intakes ranged from 14.1% for 1-d measurements to 6.94% for 6-d means. These results indicate that it should be possible to use measurements of the urine OER to identify dietary noncompliance in metabolic studies.

Adolescent↗