Developmental functional adaptation to high altitude: review.

Various approaches have been used to understand the origins of the functional traits that characterize the Andean high-altitude native. Based on the conceptual framework of developmental functional adaptation which postulates that environmental influences during the period of growth and development have long lasting effects that may be expressed during adulthood, we initiated a series of studies addressed at determining the pattern of physical growth and the contribution of growth and development to the attainment of full functional adaptation to high-altitude of low and high altitude natives living under rural and urban conditions. Current research indicate that: (a) the pattern of growth at high altitude due to limited nutritional resources, physical growth in body size is delayed but growth in lung volumes is accelerated because of hypoxic stress); (b) low-altitude male and female urban natives can attain a full functional adaptation to high altitude by exposure to high-altitude hypoxia during the period of growth and development; (c) both experimental studies on animals and comparative human studies indicate that exposure to high altitude during the period of growth and development results in the attainment of a large residual lung volume; (d) this developmentally acquired enlarged residual lung volume and its associated increase in alveolar area when combined with the increased tissue capillarization and moderate increase in red blood cells and hemoglobin concentration contributes to the successful functional adaptation of the Andean high-altitude native to hypoxia; and (e) any specific genetic traits that are related to the successful functional adaptation of Andean high-altitude natives have yet to be identified.

Developmental adaptation: where we go from here.

The concept of developmental adaptation is a powerful framework that can be used for understanding the origin of population differences in phenotypic and genotypic biological traits. There is great deal of information describing how developmental responses can shape adult biological outcomes. Specifically, current research suggest that individuals developing in stressful environments such as high altitude will attain an adult enlarged residual lung volume that contribute to the successful cardiovascular adaptation of the high-altitude Andean native. Likewise, studies on the etiology of the metabolic syndrome indicate that development under poor nutritional environments elicit efficient physiological and metabolic responses for the utilization of nutrients and energy, which become disadvantageous when the adult environmental conditions provide abundant access to food and low energy expenditure. Epigenetic research in experimental animals and retrospective research in humans confirm that environmental influences during developmental period have profound consequences on the phenotypic expression of biological and behavioral traits during adulthood. Research on epigenetics is a productive direction for human biologists concerned with understanding the origins of human biological variability.

Behavioral, environmental, metabolic and intergenerational components of early life undernutrition leading to later obesity in developing nations and in minority groups in the U.S.A.

Nutritional transition, urbanization, and physical inactivity are primary factors responsible for the worldwide epidemic of overweight/obesity (OW/OB). However, these factors fail to explain the epidemic of OW/OB in developing countries and in recent-migrants to developed countries. Among these, OW/OB is associated with short/stunted stature and coexists with undernutrition at much higher rates than is statistically expected. Changes in metabolic pathways toward reduced fat oxidation and increased metabolism of carbohydrate may explain, in part, this phenomenon. Also, intergenerational consequences of malnutrition and poor health of the mothers may lead to impaired phenotypes in their offspring. We propose a novel methodology to assess the history of early life malnutrition by assessing the sitting height ratio of the mothers. The degree of "short leggedness" reflects undernutrition when the mother was an infant/child. Collectively, behavioral, environmental, metabolic and intergenerational components of early life undernutrition may provide a more satisfactory explanation for later life obesity.

Introduction.

A basic premise of studies conducted in the 1950s and 1960s was that humans exhibited a uniform set of biological responses to the high altitude environment. Since then, investigations have been carried out in the North American Rockies, South American Andes, and the Himalayas by researchers from a variety of disciplines-biological anthropology, respiratory physiology, cardiology, hematology, and nutrition. These studies have contributed important insights for understanding the mechanisms involved in adaptation to high altitude and have revealed possible differences in the strategies of adaptation exhibited by the world's various high altitude populations. However, the findings have sometimes been slow to percolate across disciplinary boundaries, given the tradition among the biological sciences to conduct research and present findings in specialized groupings. This symposium breaks this pattern by bringing together from several disciplines investigators who are actively involved in the conduct of high altitude studies. The interaction afforded enables us to realize that understanding the process of human adaptation to high altitude requires a holistic approach whereby the expertise of various scientific disciplines needs to be utilized in a synchronized and integrated manner.

Reduction in birth weight associated with smoking among young and older-age women.

This study examined the combined effects of maternal smoking and maternal age on birth weight. A sample of 1,851 white, full-term infants (37 to 42 weeks) born to primiparous mothers ranging in age from 18 to 41 years was derived from the database of the Child Health and Development Studies (CHDS), available through the National Technical Information Service (NTIS) of the U.S. Department of Commerce. The mothers were classified into three age groups-young, middle-aged, and older-aged-corresponding respectively to values below the 15th, between the 15th and 85th, and at or above the 85th percentile of age. Analyses of the data show that the reduction in birth weight associated with maternal smoking when compared with nonsmoking averaged 181 gm for the young group (18 to 20 years), 162 gm for the middle-aged group (21 to 29 years), and 154 gm for the older-aged group (30 to 41 years). These differences are independent of total income. Hence it appears that the birth weight-reducing effect of smoking is not enhanced among women of older reproductive ages (30 to 41 years). Furthermore, the reduction in birth weight is dose responsive. That is, the greater the number of cigarettes smoked per day, the lower is the resulting mean birth weight and the higher is the proportion of low-birth-weight infants.

Relationship of serum cholesterol and truncal body fat distribution among Mexican Americans is accentuated by obesity.

The relationship of body fat distribution to serum cholesterol levels was evaluated in a sample of 3,040 Mexican Americans 18-74 years of age from the Hispanic Health and Nutrition Examination Survey (HHANES) conducted from 1982-1984. Fat distribution was determined by the ratio of trunk to extremity skinfold thicknesses, while the sum of skinfold thicknesses was used as an indicator of total body fat. Results of this study indicate that: 1) Mexican Americans are significantly fatter and have a higher trunk/extremity skinfold ratio than U.S. standards; 2) despite their higher level of total body fat and truncal fat, Mexican Americans have lower serum cholesterol levels than U.S. standards; 3) Mexican American males at the same percentile level of fatness or trunk/extremity skinfold ratio have significantly higher serum cholesterols than females, despite the fact that females have higher absolute values of fat and truncal fat than males; 4) among Mexican American males the association between truncal fat distribution and hypercholesteremia increases with level of fatness. In other words, in Mexican American males the association of truncal fat distribution with hypercholesteremia is accentuated by obesity. © 1994 Wiley-Liss, Inc.

Small for gestational age associated with short stature during adolescence.

This study examined the relationship between intrauterine growth retardation and adolescent stature in a sample of 1510 White subjects (754 males and 756 females) who were evaluated at birth and at the ages of 15, 16, and 17 years. The subjects were classified into two groups based on birthweight, small for gestational age (SGA) and appropriate for gestational age (AGA), corresponding respectively to values below the 10th, and between the 11th and 99th, percentiles of gestational age and sex. Results showed that boys and girls born prematurely (gestational age < 37 weeks of gestation) attained the same stature as those born at full term (>37 weeks of gestation). In contrast, those born SGA were significantly shorter than their counterparts born AGA. The average reduction in stature was 4.9 cm for males and 2.9 cm for females. When the analysis included adjustments for parental stature (and adolescent's age at menarche for females), the average reduction in stature equaled about 3.5 cm for males and 2.0 cm for females. It is thus concluded that the stature deficit reflects a reduction in growth rate rather than delay in maturation. © 1994 Wiley-Liss, Inc.

Coca chewing among high altitude natives: Work and muscular efficiencies of nonhabitual chewers.

The leaves of the coca plant (Erythroxylum sp.) have long been chewed by natives of the highland Andes. Folk belief is that the mild stimulant effect is indispensable as an ergogenic aid for strenuous work activities in a high altitude environment. This study explored the exercise responses of 23 nonhabitual coca chewing males who were asked to pedal a bicycle ergometer through a series of submaximal and maximal workloads both with and without coca chewing. The protocol of the exercise test was specifically designed to allow for the determination of work and muscular efficiencies during to submaximal work. The subjects showed no differences between the coca and control work protocols for VO2 max (1/min), VCO2 max (1/min), or maximal work output (watts). Further, there were no differences between coca and control work protocols in oxygen saturation (%), pulmonary ventilation (1/min), or respiratory exchange ratio (VCO2 /VO2 ) at any level of work. Coca chewing caused subjects to have a higher heart rate (bpm) and lower oxygen pulse (ml/beat) for most submaximal workloads and higher ventilatory equivalents (VE/VO2 and VE/VCO2 ) above 50% of VO2 max. Although there was a tendency for higher gross efficiencies (GE) during the coca exercise test at lower relative work levels, between 30-40% of the VO2 max, this difference did not reach significance. Mean net efficiency (NE) was higher (P=0.018) at a relative work level of ∼32% of the VO2 max for exercise with coca (23.2% vs. 20.8%). This difference was not apparent at any other work level. The mean delta efficiency (DE) was significantly lower (P = 0.012) for exercise with coca (26.7%) than for exercise without coca (28.2%). These efficiency differences suggest a muscle metabolic effect for coca chewing at low workloads whereby less oxygen is consumed by the muscle to perform a given work task. Howeve, given the difficulty of interpreting efficiency values, it is not entirely clear if the differences are indicative of a work performance benefit for coca chewing. © 1995 Wiley-Liss, Inc.

Developmental, genetic, and environmental components of lung volumes at high altitude.

Vital capacity and residual lung volume (in terms of 1/min or ml/m2 of body surface area) of 357 subjects (205 males, 152 females) was evaluated in La Paz, Bolivia, situated at 3,750 m. The sample included: (1) 37 high altitude rural natives (all male), (2) 125 high altitude urban natives (69 male, 58 female), (3) 85 Bolivians of foreign ancestry acclimatized to high altitude since birth (40 male, 45 female), (4) 63 Bolivians of foreign ancestry acclimatized to high altitude during growth (30 male, 33 female), and (5) 47 non-Bolivians of either European or North American ancestry acclimatized to high altitude during adulthood (24 male, 23 female). Results indicate that (1) all samples studied, irrespective of origin or acclimatization status, have larger lung volumes than those predicted from sea level norms; (2) the high altitude rural natives have significantly greater lung volumes (vital capacity and residual lung volume) than the high altitude urban natives and all the non-native high altitude samples; (3) males acclimatized to high altitude since birth or during growth attain similar lung volumes as high altitude urban natives and higher residual lung volumes than subjects acclimatized to high altitude during adulthood but lower than the high altitude rural natives; (4) females acclimatized to high altitude since birth or during growth attain similar lung volumes as subjects acclimatized to high altitude during adulthood; (5) age at arrival to high altitude is inversely related to residual lung volume but not vital capacity; (6) among subjects acclimatized to high altitude during growth, approximately 20-25% of the variability in residual lung volume can be explained by developmental factors; (7) among high altitude rural and urban natives, it appears that approximately 20-25% of the variability in residual lung volume at high altitude can be explained by genetic traits associated with skin reflectance and genetic traits shared by siblings; and (8) vital capacity, but not the residual lung volume, is inversely related to occupational activity level. Together these data suggest that the attainment of vital capacity at high altitude is influenced more by environmental factors, such as occupational activity level, and body composition than developmental acclimatization. On the other hand, the attainment of an enlarged residual volume is related to both developmental acclimatization and genetic factors. Am. J. Hum. Biol. 9:191-203, 1997. © 1997 Wiley-Liss, Inc.

Role of genetic and environmental factors in the increased blood pressures of Bolivian blacks.

The tendency toward hypertension or higher blood pressure is more common in blacks than whites. The factors that account for these differences are attributed to both environmental and genetic factors. To clarify this issue, an anthropological study of black and nonblack populations in the lowland village of Chicaloma, northeastern Bolivia at a midaltitude of 1,800 m was conducted. The study included 159 subjects, of which 79 were black and 80 were nonblack, 17-78 years. The study suggests the following: (1) the socioeconomic status of blacks as measured by an ownership index is greater than that of nonblacks, (2) blacks had higher average systolic and diastolic blood pressures than nonblacks and showed an age-associated increase in blood pressures, (3) the prevalence of hypertension was higher for blacks (7-6%) than nonblacks (1.3%), but three times lower than among blacks in the United States, (4) skin reflectance is inversely related to blood pressures so that contrary to what has been suggested the darker the skin color, the higher the blood pressures even at comparable levels of affluence. These findings together suggest that genetic factors predispose black individuals to increased blood pressures, but the expression of clinical hypertension is influenced by adverse unaccounted environmental factors. Am. J. Hum. Biol. 11:489-498, 1999. Copyright 1999 Wiley-Liss, Inc.

Relative leg length as a biological marker to trace the developmental history of individuals and populations: growth delay and increased body fat.

The purpose of this study was to determine whether differences in leg length index are related to differences in body fat. The study included a cross-sectional sample of 21,021 subjects ranging in age from 2 to 90 years who had anthropometric information and poverty income ratio that participated in the third National Health and Nutrition Survey (NHANES III) of the United Stated conducted during 1988-1994. Of the total 21,021 participants, 7,810 were non-Hispanic white (3,900 men and 3,910, women), 8,134 were African-American black (3,127 men and 2,889 women) and 6,237 were Mexican-American (3,221 and 3,016 women). In both males and females and in all three ethnic groups and across socio-economic status (measured by the poverty income ratio) a low leg length index is associated with increased body fat (measured by skinfold thickness) when compared with those with high leg length index. It is postulated that a low leg length index reflects the consequence of negative environmental conditions leading to growth delay. Previous studies indicate that individuals exposed both during development and adulthood to under-nutrition respond through inter-related physiological mechanisms oriented at improving energetic efficiency and low oxidation of fat. These interrelated compensatory physiological adjustments work together to promote fat storage among growth delayed individuals or populations.

Reduced rate of fat oxidation: a metabolic pathway to obesity in the developing nations.

The purpose of this article is to document the metabolic and environmental factors associated with the increased frequency of obesity in the developing nations. While the prevalence of obesity in the developed countries is caused by the increased consumption of calorie-dense foods, in the developing nations, because obesity coexists with undernutrition, additional factors are necessary to account for it. The evidence suggests that an important contributing factor for obesity in the developing nations is a reduced fat oxidation and increased metabolism of carbohydrate that has been brought about by the chronic undernutrition experienced during prenatal and postnatal growth. This shift toward a preferential metabolic use of carbohydrate rather than of fat results in an increased deposition of body fat. This tendency, along with the general decrease of energy expenditure in physical activity associated with urbanization, and the culturally mediated acceptance of fatness leads to obesity among populations from the developing nations. A joint effect of these factors is that in the developing nations obesity is associated with short stature resulting from developmental undernutrition, while in the developed countries obesity is associated with tall stature. It is hoped that future research will address the mechanisms whereby undernutrition increases the tendency toward obesity. Understanding how to modify fat oxidation could affect our ability to prevent weight gain among undernourished populations of the developing nations. Therefore, future research on the interaction of undernutrition and the development of obesity is of prime importance for anthropology concerned with the origins of human variability.