Pearl Memorial Lecture. Humans at the extremes: Exploring human adaptation to ecological and social stressors.

The field of human biology has long explored how human populations have adapted to extreme environmental circumstances. Yet, it has become increasingly clear that conditions of social stress, poverty, and lifestyle change play equally important roles in shaping human biological variation and health. In this paper, I provide a brief background on the foundational human adaptability research of the International Biological Programme (IBP) from the 1960s, highlighting how its successes and critiques have shaped current research directions in the field. I then discuss and reflect on my own field research that has examined the influence of both environmental and social stresses on human populations living in different ecosystems: the Peruvian Andes, the Siberian arctic, and the Bolivian rainforest. Finally, I consider how the papers in this special issue advance our understanding of human adaptability to extreme conditions and offer directions for future research. Drawing on our field's distinctive evolutionary and biocultural perspectives, human biologists are uniquely positioned to examine how the interplay between social and ecological domains influences the human condition.

Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure.

Obesity is caused by a prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated3,4. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.

Variation in human water turnover associated with environmental and lifestyle factors.

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking (2H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

Variability in energy expenditure is much greater in males than females.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction.

Human total, basal and activity energy expenditures are independent of ambient environmental temperature.

Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18-25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.

Brown adipose tissue thermogenesis among young adults in northeastern Siberia and Midwest United States and its relationship with other biological adaptations to cold climates.

OBJECTIVES: Recent research suggests that brown adipose tissue (BAT) plays a functional role in non-shivering thermogenesis; however, few studies have examined population variation in BAT or its relationship with other mechanisms of adaptation to cold stress. This study characterized BAT thermogenesis and other adaptive responses to low temperatures among Indigenous Siberian young adults and young adults living near Chicago, IL. MATERIALS AND METHODS: We recruited 72 Yakut participants (42 females; 30 males) and 54 participants in Evanston, IL (40 females; 14 males). Anthropometric dimensions and resting metabolic rate (RMR) were measured, and we calculated percent divergence in RMR from expected values (divRMR). We also quantified change in supraclavicular temperature, sternum temperature, and energy expenditure after a mild cooling condition. RESULTS: Participants in Yakutia were less likely to shiver during the cooling condition (p < .05) and exhibited significantly greater evidence of BAT thermogenesis, warmer sternum temperatures, and higher divRMR than participants in Evanston (p < .05). Additionally, the relationship between change in supraclavicular temperature and energy expenditure differed between the two samples. CONCLUSIONS: Yakut young adults displayed greater evidence of BAT thermogenesis in response to mild cooling compared with young adults living near Chicago, IL. Furthermore, the relationship between BAT thermogenesis and change in energy expenditure appears to be stronger among Yakut adults. Adults that exhibited greater metabolic response to cold stress, such as higher BAT thermogenesis and divRMR, maintained warmer sternum temperatures. These results highlight the degree to which adaptation to cold climates involves multiple integrated biological pathways.

Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition.

Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but not children. Bivariate Bayesian mixed models show no among or within-individual correlation between body composition (fat mass or percentage) and unadjusted TEE in adults. For adults aged 20-60 y (N = 267; time interval: 7.4 ± 12.2 weeks), increases in adjusted TEE are associated with weight gain but not with changes in body composition; results are similar for subjects with intervals >4 weeks (N = 53; 29.1 ± 12.8 weeks). This suggests low TEE is not a risk factor for, and high TEE is not protective against, weight or body fat gain over the time intervals tested.

The evolutionary significance of human brown adipose tissue: Integrating the timescales of adaptation.

While human adaptability is regarded as a classical topic in anthropology, recent work provides new insight into metabolic adaptations to cold climates and the role of phenotypic plasticity in human evolution. A growing body of literature demonstrates that adults retain brown adipose tissue (BAT) which may play a role in non-shivering thermogenesis. In this narrative review, we apply the timescales of adaptation framework in order to explore the adaptive significance of human BAT. Human variation in BAT is shaped by multiple adaptive modes (i.e., allostasis, acclimatization, developmental adaptation, epigenetic inheritance, and genetic adaptation), and together the adaptive modes act as an integrated system. We hypothesize that plasticity in BAT facilitated the successful expansion of human populations into circumpolar regions, allowing for selection of genetic adaptations to cold climates to take place. Future research rooted in human energetics and biocultural perspectives is essential for understanding BAT's adaptive and health significance.

The effect of gender targeting of food transfers on child nutritional status: Experimental evidence from the Bolivian Amazon.

Some research suggests women are more likely to allocate additional resources to their children than are men. This perception has influenced policies such as in-kind food transfer programs and cash transfer programs, which often target women recipients. We assess whether targeting in-kind rice transfers to female versus male adult household members has a differential impact on children's short-run nutritional status. We estimate the impacts of transfers of edible rice and rice seeds, randomly allocated to female or male adults, on three anthropometric indicators: BMI-for-age, arm-muscle area, and triceps skinfold thickness. The trial includes 481 children aged 3-11 years in a horticultural-foraging society of native Amazonians in Bolivia. On average, the gender of the transfer recipient does not influence child anthropometric dimensions, possibly due to norms of cooperation and sharing within and between households. We find limited evidence of heterogeneity in impacts. Transfers to women help children who were growth stunted at baseline to partially catch-up to their better-nourished age-sex peers and help boys (but not girls) and children in higher-income households increase their BMI-for-age. The results of this research point to the importance of considering cultural context in determining if allocating food transfers according to gender are most effective.

Physical activity and fat-free mass during growth and in later life.

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass. OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age. METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution. RESULTS: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively. CONCLUSIONS: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults.

Daily energy expenditure through the human life course.

Total daily energy expenditure ("total expenditure") reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span.

Energy compensation and adiposity in humans.

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.

Evidence for a sensitive period of plasticity in brown adipose tissue during early childhood among indigenous Siberians.

OBJECTIVES: Evolutionary theorists have debated the adaptive significance of developmental plasticity in organisms with long lifespans such as humans. This debate in part stems from uncertainty regarding the timing of sensitive periods. Does sensitivity to environmental signals fluctuate across development or does it steadily decline? We investigated developmental plasticity in brown adipose tissue (BAT) among indigenous Siberians in order to explore the timing of phenotypic sensitivity to cold stress. METHODS: BAT thermogenesis was quantified using infrared thermal imaging in 78 adults (25 men; 33 women). Cold exposure during gestation, infancy, early childhood, middle childhood, and adolescence was quantified using: (1) the average ambient temperature across each period; (2) the number of times daily temperature dropped below -40°F during each period. We also assessed past cold exposure with a retrospective survey of participation in outdoor activities. RESULTS: Adult BAT thermogenesis was significantly associated with the average temperature (p = 0.021), the number of times it was below -40°F (p = 0.026), and participation in winter outdoor activities (p = 0.037) during early childhood. CONCLUSIONS: Our results suggest that early childhood represents an important stage for developmental plasticity, and that culture may play a critical role in shaping the timing of environmental signals. The findings highlight a new pathway through which the local consequences of global climate change may influence human biology, and they suggest that ambient temperature may represent an understudied component of the developmental origins of health and disease.

A standard calculation methodology for human doubly labeled water studies.

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.