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Results for “Caloric Restriction”

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PubMed2002

Hepatic reduction of insulin-like growth factor (IGF)-I and IGF binding protein-3 that results from fasting is not attenuated in genetically obese rats.

Fasting or caloric restriction causes substantial reductions in serum IGF-I in normal weight humans and animals, and reductions of liver IGF-I and IGFBP-3 mRNAs in animals. Obese humans, however, have attenuated and delayed decrements in IGF-I in serum when subjected to caloric restriction. Obese Zucker rats show a clear tendency to preserve body protein during fasting. To determine whether obesity opposes the effects of fasting on IGF-I and IGFBP-3, and thereby contributes to preservation of lean tissue, we have examined the effect of 72 h of fasting on IGF-I and IGFBP-3 in lean and obese Zucker rats. We observe that between lean and obese animals, fasting for 72 h produces similar decrements in body weight, serum IGF-I, liver IGF-I mRNA, serum IGFBP-3 and liver IGFBP-3 mRNA. Our finding that the reduction of IGF-I and IGFBP-3 in liver that results from 72 h of fasting is not attenuated in obese Zucker rats raises the possibility that conservation of lean tissue in these animals during fasting is not related to the hepatic production of IGF-I and IGFBP-3.

Journal Article↗

PubMed1985

Diet and exercise training effects on resting metabolic rate.

The decline in resting metabolic rate (RMR) during periods of caloric restriction is a well documented phenomenon. The purpose of this study was to determine if either 30 min of daily self-selected aerobic activity (Group D) or prescribed exercise training performed every other day (Group P) for 12 weeks can prevent the decrease in RMR during caloric restriction for weight loss. Seventy-eight adult subjects (38 M, 40 F) whose weights were 15-35 percent above the upper limit for age, sex and frame were randomly assigned to three treatment groups. All three groups followed the same 1200, 1500 or 1800 kcal/d (5023, 6279, 7534 kJ) diet exchange plan. Group C (Control) followed no exercise program, while D and P exercised as described above. Maximal oxygen consumption (VO2 max, m10(2)/kg X min-1) predicted from the Bruce Test increased by 0.08 +/- 7, 9 +/- 12 and 12 +/- 9 percent in groups C, D and P, respectively. The increases for D and P were significantly higher than for C (P less than 0.01). RMR (m10(2)/kg X min-1) increased by 2 +/- 9, 4 +/- 7 and 10 +/- 9 percent in groups C, D and P respectively. The percent change for group P was significantly greater than that for groups C and D (P less than 0.05). There was a significant relationship across all subjects between the % delta in VO2 max and % delta in RMR (r = 0.307, P less than 0.01). However, the association between these two variables was stronger for females than for males.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Effects of nutrition on disease and life span. I. Immune responses, cardiovascular pathology, and life span in MRL mice.

Mice of the autoimmune, lymphoproliferative strain MRL/lpr and the congenic, nonlymphoproliferative strain MRL/n were fed one of six diets from weaning on-ward. These mice were sacrificed at 3 or 5 months of age. Low fat diets resulted in lower cholesterol and higher triglyceride levels than did cholesterol-containing high-fat diets. Caloric restriction of MRL/lpr mice was associated with an increased plaque-forming cell response to trinitrophenylated polyacrylamide beads, less lymphoproliferation, and less severe glomerulonephritis. Diet did not affect the incidence of autoimmune vasculitis in MRL/lpr mice sacrificed at 5 months. MRL/lpr mice fed a low-fat, calorically restricted diet from 5 months of age to death lived longer than mice which were fed ad libitum a cholesterol-containing, high-fat diet. At death, MRL/lpr mice fed the former diet had the autoimmune vasculitis which had been evident in mice killed at 5 months, whereas mice fed the latter diet, in addition to the vasculitis, had a high incidence of atherosclerotic lesions of intrarenal and aortic branch arteries.

Animal Nutritional Physiological Phenomena↗

PubMed2006

Influences of calorie restriction and age on energy expenditure in the rhesus monkey.

Caloric restriction (CR) is known to retard the aging process, and a marker of aging is decreased energy expenditure (EE). To assess longitudinal effects of CR on EE in rhesus monkeys (Macaca mulatta), data from 41 males (M) and 26 females (F) subjected to 9 or 15 yr of CR were studied. EE and body composition of monkeys 11-28 yr of age were measured using indirect calorimetry and dual X-ray absorptiometry. Total EE (24-h EE) was divided into daytime (day EE), nighttime (night EE), and daytime minus nighttime (D - N EE). M calorie-restricted monkeys showed a lower 24-h EE (means +/- SD = 568 +/- 96 kcal/day, P < 0.0001) than controls (C; 630 +/- 129 kcal/day). Calorie-restricted M had a lower night EE (difference = 36 kcal P < 0.0001) compared with C M, but after adjusting for FFM and FM, night EE was not different between calorie-restricted and C males (P = 0.72). The 24-h EE decreased with age (13 kcal decrease/yr, P < 0.0001), but there was no difference between CR and C. Adjusted for FFM and FM, D - N EE decreased with age (9 kcal/yr, P < 0.0001), with no interaction with age (P = 0.72). The F were compared with age-matched M selected from the male cohort. F had a lower 24-h EE (496 +/- 84 kcal/day) than M (636 +/- 139 kcal/day) (P < 0.0001). Adjusting for FFM and FM, night EE was lower in F compared with M (difference = 18 kcal, P = 0.077). Night EE did not differ between calorie-restricted and C younger monkeys after adjusting for FFM and FM. In conclusion, CR did not alter the age-related decrease in EE with CR.

Age Factors↗

PubMed1989

The effects of altered nutritional status upon insulin-like growth factors and their binding proteins in neonatal rats.

To investigate the role of nutrition in the regulation of IGFs during the perinatal period, 10-d-old rats were infused intravenously with various concentrations of nutrients for 24 h. Breast-fed litter mates served as controls. The effect of caloric intake on concentrations of IGF-I and IGF-II as well as IGF-binding proteins in serum, liver, and brain of neonatal rats was studied. A total of 45 rats from 10 litters was infused with solutions ranging from a caloric intake of 0 (saline) to 75% (glucose, amino acids, and lipids) of the estimated intake of control rats. In serum, both IGF-I and -II concentrations fell markedly in response to fasting. Serum IGF-II levels were linearly related to caloric intake in the pooled data from all groups. Concentrations of IGF-II, but not IGF-I, in liver and brain were depressed by caloric restriction. In contrast to the fall in IGF concentrations, activity of IGF-associated binding proteins rose in serum and in liver cytosol 2- to 4-fold in response to decreased nutrient intake. In serum, but not liver, the rise in binding protein activity was inversely related to to caloric intake. In liver, cytosol, but not serum, the rise in binding protein activity was inversely related to total serum amino acid concentration. Thus, IGF concentrations in preweanling rats change in response to alterations of nutrient intake. The fasting induced decrements in IGF levels, as well as the elevations in IGF-associated binding protein activity, may serve as a protective mechanism to depress growth in times of caloric restriction.

Animals↗

PubMed2006

Weight-control practices among U.S. adults, 2001-2002.

BACKGROUND: Approximately $50 billion a year is spent by Americans on weight-loss products and services. Despite the high cost, few national studies have described specific weight-loss and weight-maintenance practices among U.S. adults. This analysis describes the use of specific practices by U.S. adults who tried to lose weight or tried only not to gain weight during the previous 12 months. METHODS: Data were analyzed from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) conducted on a nationally representative sample of the U.S. population. This study focused on adults aged 20 years or older who were both interviewed and examined (n =5027). RESULTS: Fifty-one percent of U.S. adults tried to control their weight in the previous 12 months, including those who tried to lose weight (34% of men, 48% of women) and those who tried only not to gain weight (11% vs 10%, respectively). Among 2051 adults who tried to control their weight, the top four practices were the same: ate less food (65% among those who tried to lose weight, 52% among those who tried only not to gain weight); exercised (61% vs 46%, respectively); ate less fat (46% vs 42%); and switched to foods with lower calories (37% vs 36%). Less than one fourth combined caloric restriction with the higher levels of physical activity (300 or more minutes per week) recommended in the 2005 dietary guidelines by the U.S. Department of Health and Human Services and U.S. Department of Agriculture. CONCLUSIONS: Although weight control is a common concern, most people who try do not use recommended combinations of caloric restriction and adequate levels of physical activity.

Adult↗

PubMed2006

Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones.

CONTEXT: Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T(3) hormone may increase life span by conserving energy and reducing free-radical production. OBJECTIVE: The objective of the study was to assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women. DESIGN, SETTING, AND PARTICIPANTS: In this study, serum thyroid hormones were evaluated in 28 men and women (mean age, 52 +/- 12 yr) consuming a CR diet for 3-15 yr (6 +/- 3 yr), 28 age- and sex-matched sedentary (WD), and 28 body fat-matched exercising (EX) subjects who were eating Western diets. MAIN OUTCOME MEASURES: Serum total and free T(4), total and free T(3), reverse T(3), and TSH concentrations were the main outcome measures. RESULTS: Energy intake was lower in the CR group (1779 +/- 355 kcal/d) than the WD (2433 +/- 502 kcal/d) and EX (2811 +/- 711 kcal/d) groups (P < 0.001). Serum T(3) concentration was lower in the CR group than the WD and EX groups (73.6 +/- 22 vs. 91.0 +/- 13 vs. 94.3 +/- 17 ng/dl, respectively) (P < or = 0.001), whereas serum total and free T(4), reverse T(3), and TSH concentrations were similar among groups. CONCLUSIONS: Long-term CR with adequate protein and micronutrient intake in lean and weight-stable healthy humans is associated with a sustained reduction in serum T(3) concentration, similar to that found in CR rodents and monkeys. This effect is likely due to CR itself, rather than to a decrease in body fat mass, and could be involved in slowing the rate of aging.

Adult↗

PubMed1990

Hamster adipocyte alpha 2-adrenoceptor changes during fat mass modifications are not directly dependent on adipose tissue norepinephrine content.

It is questioned whether alterations of the sympathetic nervous system can explain the specific increment of the adipocyte alpha 2-adrenoceptor observed during white adipose tissue (WAT) enlargement and fat cell size increment. The impact of a 6-hydroxydopamine-induced sympathectomy, validated by determination of the WAT norepinephrine content, was tested on isolated white fat cell alpha 2-adrenoceptor function and binding [( 3H]RX 821002 and [3H]UK 14304 binding). Chemical sympathectomy of standard adult hamsters, neither alters the alpha 2-adrenergic-dependent antilipolysis nor the adipocyte alpha 2-adrenergic binding. A slight hypersensitivity of the beta 1-adrenergic lipolytic response was observed, without modification in beta-adrenergic binding [( 125I]cyanopindolol binding). Compared with controls, caloric restriction (10 days) of adult hamsters induced a large decrease in adipocyte alpha 2-adrenoceptor (P less than 0.001) with a parallel decrement in the mean fat cell size (P less than 0.001) and alpha 2-adrenergic responsiveness while there was no significant variation of the WAT norepinephrine content (on a per pad basis). 6-Hydroxydopamine treatment of the restricted animals (from day 6 to day 9) induced a higher preservation of adipocyte alpha 2-adrenoceptor density (P less than 0.001), no change in alpha 2-adrenergic responsiveness, and higher preservation of mean fat cell size (P less than 0.05) than in the restricted only animals. No significant modification in the beta-adrenergic binding was observed whatever the conditions. It was concluded that the specific increment in the adipocyte alpha 2-adrenoceptor during fat mass enlargement was not directly dependent on sympathetic nervous system alterations. Nevertheless, the sympathetic-dependent mobilization of the fat stores, after induction of caloric restriction, can indirectly modulate the alpha 2-adrenoceptor density in the adipocyte by promoting changes in white fat cell size.

Adipose Tissue↗

PubMed2001

The case for supporting basic research in gerontology.

Basic research on aging has moved well beyond describing the aging of physiological systems and developing theories of aging, to the pursuit of mechanistic answers to questions such as: Why do we age? Why do individuals within a population age differently? Why do different species have such different life spans? How do aging changes increase the risk of developing age-related disease? and Can we develop safe and effective interventions to reduce age-related disability? Two general areas of research promise to provide answers to these questions. One is the attempt to understand the mechanisms by which caloric restriction extends longevity and delays the onset of age-related disease. The other is the identification of genes which strongly influence the rate of aging in various animal model systems. Recent results in the latter area of research are providing new insights into the answers to these central aging questions and may help us understand how caloric restriction retards aging.

Aged↗

PubMed1990

Testosterone replacement fails to reverse the adverse effects of streptozotocin-induced diabetes on sexual behavior in the male rat.

The ability of testosterone to reverse the adverse effects of streptozotocin-induced (STZ) diabetes on male sexual function was tested in adult male rats. Treatment with STZ (50 mg/kg) led to a significant reduction of plasma testosterone (T) levels and in the number of rats exhibiting ejaculatory behavior in a 30-minute test period. A similar reduction in T levels and ejaculatory behavior was seen in rats subjected to caloric restriction to mimic the weight loss seen in the STZ-treated rats. T-replacement (200 micrograms/day) restored T levels to those seen in control animals, but did not reverse the adverse effects of STZ on copulatory behavior. STZ-induced changes in copulatory behavior were associated with changes in hypothalamic LHRH levels and catecholamine turnover. Caloric restriction also caused endocrine and neuroendocrine changes, but they were not similar to those seen in STZ rats suggesting that these two treatments affect copulatory behavior by different mechanisms.

Animals↗

PubMed1993

Sympathoadrenal activity and obesity: physiological rationale for the use of adrenergic thermogenic drugs.

The sympathetic nervous system is a major regulator of dietary thermogenesis in laboratory animals and humans. Since a lowered metabolic rate predisposes to the development of obesity, and since caloric restriction suppresses sympathetic activity, a role for adrenergic agonists in the treatment of obesity has a well established physiological rationale. Although diminished sympathetic activity does not appear to underlie obesity in most circumstances in humans, to the extent that adrenergic agonists increase metabolic rate in the obese they may be useful as pharmacologic adjuncts to low energy diets. During caloric restriction the significant diminution in sympathetically mediated thermogenesis antagonizes weight loss; this decrease in metabolic rate may be overcome by sympathomimetic amines thereby increasing the effectiveness of low energy diets. Since smoking stimulates the sympathoadrenal system and increases thermogenesis, smoking cessation, with its attendant fall in sympathoadrenal activity and decrease in metabolic rate, fosters weight gain. Adrenergic agonists may be useful in this circumstance as well.

Adrenal Glands↗

PubMed2002

Akt signaling mediates postnatal heart growth in response to insulin and nutritional status.

Akt is a serine-threonine kinase that mediates a variety of cellular responses to external stimuli. During postnatal development, Akt signaling in the heart was up-regulated when the heart was rapidly growing and was down-regulated by caloric restriction, suggesting a role of Akt in nutrient-dependent regulation of cardiac growth. Consistent with this notion, reductions in Akt, 70-kDa S6 kinase 1, and eukaryotic initiation factor 4E-binding protein 1 phosphorylation were observed in mice with cardiac-specific deletion of insulin receptor gene, which exhibit a small heart phenotype. In contrast to wild type animals, caloric restriction in these mice had little effect on Akt phosphorylation in the heart. Furthermore, forced expression of Akt1 in these hearts restored 70-kDa S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 phosphorylation to normal levels and rescued the small heart phenotype. Collectively, these results indicate that Akt signaling mediates insulin-dependent physiological heart growth during postnatal development and suggest a mechanism by which heart size is coordinated with overall body size as the nutritional status of the organism is varied.

Aging↗

PubMed2006

Susceptibility to induced and spontaneous carcinogenesis is increased in fatless A-ZIP/F-1 but not in obese ob/ob mice.

Obesity is typically associated with increased tumor susceptibility, whereas caloric restriction, a regimen resulting in leanness, inhibits carcinogenesis. The link between adiposity and malignancies suggests that adipose tissue may influence carcinogenesis. An adipose tissue hormone, leptin, could be procarcinogenic because it stimulates proliferation in various tissues and tumor cell lines. Leptin may contribute to the correlation between adiposity and malignancies as its levels are usually increased in obese subjects and reduced by caloric restriction. We hypothesized that leptin deficiency, despite obesity, would inhibit carcinogenesis in leptin-null ob/ob mice and tested this hypothesis in two models: (a) two-stage skin carcinogenesis initiated by 7,12-dimethylbenz(a)anthracene and promoted by phorbol 12-myristate 13-acetate (PMA) and (b) p53 deficiency. Contrary to a typical association between obesity and enhanced carcinogenesis, obese ob/ob mice developed induced skin papillomas and spontaneous p53-deficient malignancies, mostly lymphomas, similarly to their lean littermates. Surprisingly, lipodystrophic (ZIP) mice that had very little both adipose tissue and leptin were highly susceptible to carcinogenesis. Hyperphagia, hyperinsulinemia, and hyperglycemia are unlikely to have contributed significantly to the enhancement of carcinogenesis in ZIP mice because similarly hyperphagic, hyperinsulinemic, and hyperglycemic ob/ob mice had normal susceptibility to carcinogenesis. Our data suggest that, in contrast to a well-known correlation between obesity and cancer, the direct effect of adipose tissue may rather be protective.

Animals↗

PubMed2005

Physical activity, obesity and cardiovascular diseases.

Sedentary lifestyle and overweight are major public health, clinical, and economical problems in modern societies. The worldwide epidemic of excess weight is due to imbalance between physical activity and dietary energy intake. Sedentary lifestyle, unhealthy diet, and consequent overweight and obesity markedly increase the risk of cardiovascular diseases. Regular physical activity 45-60 min per day prevents unhealthy weight gain and obesity, whereas sedentary behaviors such as watching television promote them. Regular exercise can markedly reduce body weight and fat mass without dietary caloric restriction in overweight individuals. An increase in total energy expenditure appears to be the most important determinant of successful exercise-induced weight loss. The best long-term results may be achieved when physical activity produces an energy expenditure of at least 2,500 kcal/week. Yet, the optimal approach in weight reduction programs appears to be a combination of regular physical activity and caloric restriction. A minimum of 60 min, but most likely 80-90 min of moderate-intensity physical activity per day may be needed to avoid or limit weight regain in formerly overweight or obese individuals. Regular moderate intensity physical activity, a healthy diet, and avoiding unhealthy weight gain are effective and safe ways to prevent and treat cardiovascular diseases and to reduce premature mortality in all population groups. Although the efforts to promote cardiovascular health concern the whole population, particular attention should be paid to individuals who are physically inactive, have unhealthy diets or are prone to weight gain. They have the highest risk for worsening of the cardiovascular risk factor profile and for cardiovascular disease. To combat the epidemic of overweight and to improve cardiovascular health at a population level, it is important to develop strategies to increase habitual physical activity and to prevent overweight and obesity in collaboration with communities, families, schools, work sites, health care professionals, media and policymakers.

Adipose Tissue↗

PubMed1990

Aging: hypothalamic catecholamines, neuroendocrine-immune interactions, and dietary restriction.

The decline in hypothalamic catecholamine (CA) activity with age in rats leads to a reduction in hormone secretion by the neuroendocrine system, and results in decreased reproductive function, a reduction in protein synthesis, development of numerous mammary and pituitary tumors, and probably contributes to the decline in immune function. Some of these same effects can be produced in young rats by administration of drugs that lower hypothalamic CA activity. Administration of drugs to old rats that elevate hypothalamic CA activity can inhibit or reverse the reproductive decline, increase protein synthesis, induce regression of mammary and pituitary tumors, decrease disease incidence, probably elevate immune function, and significantly extend the life span. Therefore, hypothalamic CA have a critical role in the development of aging processes. When young or mature rats or mice are fed a caloric restricted diet, aging processes are inhibited and life span is significantly lengthened. These effects are believed to be mediated primarily via the neuroendocrine system, since calorie restriction results in decreased secretion of hypothalamic, pituitary, and target gland hormones. The decline in hormone secretion leads to a reduction in most body functions, lowers whole body metabolism, and reduces gene expression, and thereby results in a decreased rate of aging of body tissues and longer life. These effects of caloric restriction can be counteracted by administration of hormones, providing evidence that the favorable effects on aging are mediated by reducing hormone secretion.

Aging↗

PubMed1978

Understanding postoperative fatigue.

Performance characteristics of the central nervous, cardiovascular, respiratory and muscular systems in man postoperatively have received little investigative attention, despite the well known syndrome of postoperative fatigue. The impairmen in perception and psychomotor skills that has been shown to result from caloric restriction, bedrest, sedation and sleep deprivation suggests that a similar deficit may occur after surgical procedures. After a simple elective surgical procedure, maximal oxygen uptake decreases and the adaptability of heart rate to submaximal workloads is impaired. Similar deleterious effects on cardiorespiratory performance have been documented with starvation and bedrest; an understanding of cardiorespiratory performance postoperatively awaits further investigation. Maximal muscular force of contraction is also impaired by caloric restriction and bedrest, suggesting that similar effects may be seen in the postoperative state, although this has not been studied. A better understanding of the syndrome of postoperative fatigue could be achieved by a descriptive analysis of physiologic performance postoperatively. Such descriptive data could form the basis for objective evaluation of therapeutic measures intended to improve performance, such as nutritional supplementation and pharmacologic intervention. The observation that exercise with the patient in the supine position may decrease the impairment in maximal aerobic power otherwise expected in immobilized patients suggests that controlled exercise therapy may be of value in reducing physiologic impairment postoperatively.

Central Nervous System↗

PubMed1976

Efficacy of diet and exercise in the reduction of serum cholesterol and triglyceride in free-living adult males.

Young males with levels of serum cholesterol or triglyceride in the upper quartile of the distribution for volunteers tested, participated in a program designed to determine the effect of diet and exercise on serum lipids. Dietary modifications involved caloric restriction superimposed on either the National Institutes of Health (NIH) recommendations for type II or IV hyperlipoproteinemia, as appropriate, or superimposed on a fat-controlled regimen in which fat of an unspecified nature was restricted to 30% of total calories. Participants with elevated levels of cholesterol responded significantly better when instructed in the diet meeting NIH criteria, 21% change in cholesterol, than when instructed in a diet controlled in fat, 11% change in cholesterol. For those with elevated levels of triglyceride, the NIH type IV diet was no more effective at the end of 6 months than the diet controlled in fat where caloric restriction was a part of both dietary regimens. The mean change in triglyceride for this group was 32%. Those with elevated levels of both cholesterol and triglyceride were less amenable to change than those with a single hyperlipidemia. For some diagnostic types, the results were suggestive of a beneficial effect of exercise in addition to diet in accelerating or maintaining reductions in serum lipids.

Adult↗

PubMed1995

Plasma endothelin-1 levels in obese hypertensive and normotensive men.

Plasma endothelin-1 (ET-1) levels were studied in 15 obese hypertensive (mean age 48.5 +/- 3.9 years) and 15 obese normotensive men (mean age 49.5 +/- 3.6 years) before and after weight loss due to an 800 kcal/day diet lasting 12 weeks. Circulating peptide concentrations were also assessed in nonobese hypertensive (n = 11) and normotensive men (n = 12). Baseline plasma ET-1 levels were similar in obese hypertensive (0.87 +/- 0.22 pg/ml) and obese normotensive men (0.91 +/- 0.30 pg/ml). In seven obese hypertensive men, caloric restriction normalized blood pressure levels (systolic: from 166.6 +/- 8.1 to 145.0 +/- 6.3 mmHg, P < 0.0001; diastolic: from 106.6 +/- 5.1 to 89.1 +/- 2.0 mmHg, P < 0.0001) and decreased body mass index (BMI) (from 33.4 +/- 1.6 to 29.6 +/- 2.1 kg/m2, P < 0.002) and plasma ET-1 levels (from 0.93 +/- 0.21 to 0.64 +/- 0.26 pg/ml, P < 0.05). In the remaining obese hypertensive men (n = 8), blood pressure levels were not normalized by caloric restriction despite a significant decrease of BMI and plasma ET-1 levels (from 0.83 +/- 0.23 to 0.60 +/- 0.16 pg/ml, P < 0.04). Weight loss also significantly decreased BMI and ET-1 (from 0.91 +/- 0.30 to 0.65 +/- 0.19 pg/ml, P < 0.01) in obese normotensive men. Baseline ET-1 and fasting insulin levels were significantly correlated in obese hypertensive (r = 0.518, P < 0.05) and obese normotensive men (r = 0.535, P < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗