Christopher W. Kuzawa

Epigenetics and the embodiment of race: developmental origins of US racial disparities in cardiovascular health.

The relative contribution of genetic and environmental influences to the US black‐white disparity in cardiovascular disease (CVD) is hotly debated within the public health, anthropology, and medical communities. In this article, we review evidence for developmental and epigenetic pathways linking early life environments with CVD, and critically evaluate their possible role in the origins of these racial health disparities. African Americans not only suffer from a disproportionate burden of CVD relative to whites, but also have higher rates of the perinatal health disparities now known to be the antecedents of these conditions. There is extensive evidence for a social origin to prematurity and low birth weight in African Americans, reflecting pathways such as the effects of discrimination on maternal stress physiology. In light of the inverse relationship between birth weight and adult CVD, there is now a strong rationale to consider developmental and epigenetic mechanisms as links between early life environmental factors like maternal stress during pregnancy and adult race‐based health disparities in diseases like hypertension, diabetes, stroke, and coronary heart disease. The model outlined here builds upon social constructivist perspectives to highlight an important set of mechanisms by which social influences can become embodied, having durable and even transgenerational influences on the most pressing US health disparities. We conclude that environmentally responsive phenotypic plasticity, in combination with the better‐studied acute and chronic effects of social‐environmental exposures, provides a more parsimonious explanation than genetics for the persistence of CVD disparities between members of socially imposed racial categories. Am. J. Hum. Biol., 2009.

Adipose tissue in human infancy and childhood: An evolutionary perspective

Humans diverge from most mammals, including nonhuman primates, by depositing significant quantities of body fat in utero and are consequently one of the fattest species on record at birth. While explanations for the fat layer of human neonates have commonly assumed that it serves as insulation to compensate for hairlessness, empirical support for this hypothesis is presently weak. Whether the tissues abundance at birth and growth changes in adiposity during infancy and childhood might be explained in light of its role as energy buffer has not been assessed, and this possibility is explored through development of a model of fat function and growth centered on two related hypotheses. The first is that the greater adiposity of human neonates is at least partially explainable as an accompaniment of the enlarged human brain, which demands a larger energy reserve to ensure that its obligatory needs are met when the flow of resources from mother or other caretakers is disrupted. The second is that age-related changes in the likelihood of experiencing such disruption have influenced the pattern of investment in the tissue, reflected today in peak adiposity during infancy and a decline to a leaner childhood period. Nutritional disruption is common at birth and until lactation is established, during which time human newborns survive from fats deposited prenatally, suggesting one possible explanation for the early onset of fat deposition. At weaning, the transition from breast milk to supplemental foods and the parallel transition from maternal to endogenous immune protection interact to increase the frequency and impact of nutritional disruption, and this may help explain why newborns devote roughly 70% of growth expenditure to fat deposition during the early postnatal months. Evidence is presented that fat stores are mobilized during infections, hinting at one possible mechanism underlying the association between nutritional status and infectious morbidity and mortality among infants in nutritionally stressed human populations. Consistent with the proposed hypothesis, well-fed infants acquire peak fat reserves by an age of peak prevalence of malnutrition, infectious disease, and fat reserve depletion in less-buffered contexts, and childhood--characterized by minimal investment in the tissue--is a stage of reduced risk of energy stress. The model presented here foregrounds energy storage in adipose tissue as an important life-history strategy and a means to modify mortality risk during the nutritionally turbulent period of infancy.

Longitudinal evidence that fatherhood decreases testosterone in human males

In species in which males care for young, testosterone (T) is often high during mating periods but then declines to allow for caregiving of resulting offspring. This model may apply to human males, but past human studies of T and fatherhood have been cross-sectional, making it unclear whether fatherhood suppresses T or if men with lower T are more likely to become fathers. Here, we use a large representative study in the Philippines (n = 624) to show that among single nonfathers at baseline (2005) (21.5 ± 0.3 y), men with high waking T were more likely to become partnered fathers by the time of follow-up 4.5 y later (P < 0.05). Men who became partnered fathers then experienced large declines in waking (median: −26%) and evening (median: −34%) T, which were significantly greater than declines in single nonfathers (P < 0.001). Consistent with the hypothesis that child interaction suppresses T, fathers reporting 3 h or more of daily childcare had lower T at follow-up compared with fathers not involved in care (P < 0.05). Using longitudinal data, these findings show that T and reproductive strategy have bidirectional relationships in human males, with high T predicting subsequent mating success but then declining rapidly after men become fathers. Our findings suggest that T mediates tradeoffs between mating and parenting in humans, as seen in other species in which fathers care for young. They also highlight one likely explanation for previously observed health disparities between partnered fathers and single men.

Prolonged myelination in human neocortical evolution

Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.

Cohort Profile: The Cebu Longitudinal Health and Nutrition Survey

The Cebu Longitudinal Health and Nutrition Survey (CLHNS) was originally conceptualized as an interdisciplinary study of infant-feeding patterns, particularly the overall sequencing of feeding events (milks and complementary foods), the factors affecting feeding decisions and how feeding patterns affect the infant, mother and household. The idea was to study these topics within as natural a setting as possible and to analyse how infant-feeding decisions interacted with social, economic and environmental factors to affect health, nutritional, demographic and economic outcomes. The study was subsequently expanded to cover a wide range of maternal and child health and demographic issues that could be well studied using a prospective, community-based sample. The study was initially the product of collaboration among researchers at the Carolina Population Center at the University of North Carolina at Chapel Hill (led by B.M.P. with J.S.A. and D.K.G.), The Office of Population Studies Foundation at the University of San Carlos in Cebu, Philippines (led by the late Director Wilhelm Fleiger) and the Nutrition Center of the Philippines (led by Florentino Solon). L.S.A. took the lead for follow-up surveys beginning in 1990. Later, the study team was expanded to include researchers presently at the Northwestern University (C.W.K. and T.M.D.) and Johns Hopkins University (M.J.H.). The study was initiated with cooperation and approval from the Cebu Department of Health. The CLHNS website includes a full list of investigators and their affiliations. The CLHNS was one of the first large-scale, population-based surveys designed with a conceptual framework in mind. The guiding framework was adapted from Mosley and Chen’s health determinants model, which posits that underlying community-, householdand individual-level variables affect a set of proximate health behaviours which, in turn, influence health outcomes such as growth and infectious disease morbidity and mortality. The study was designed by a highly interdisciplinary group of economists, sociologists, nutritionists, demographers and physicians. The CLHNS has been funded by a large number of government and non-government organizations (listed in the Funding section).

Metabolic costs and evolutionary implications of human brain development

Significance The metabolic costs of brain development are thought to explain the evolution of humans’ exceptionally slow and protracted childhood growth; however, the costs of the human brain during development are unknown. We used existing PET and MRI data to calculate brain glucose use from birth to adulthood. We find that the brain’s metabolic requirements peak in childhood, when it uses glucose at a rate equivalent to 66% of the body’s resting metabolism and 43% of the body’s daily energy requirement, and that brain glucose demand relates inversely to body growth from infancy to puberty. Our findings support the hypothesis that the unusually high costs of human brain development require a compensatory slowing of childhood body growth. The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain’s glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain–body metabolic trade-offs using the ratios of brain glucose uptake to the body’s resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

Early origins of inflammation: microbial exposures in infancy predict lower levels of C-reactive protein in adulthood

Ecological factors are important determinants of the development and function of anti-pathogen defences. Inflammation is a central part of innate immunity, but the developmental factors that shape the regulation of inflammation are not known. We test the hypothesis that microbial exposures in infancy are associated with high sensitivity C-reactive protein (CRP) in adulthood using prospective data from a birth cohort in the Philippines (n = 1461). Lower birth weight was associated with increased CRP, consistent with a role for inflammation in the widely documented inverse relationship between birth weight and adult cardiovascular diseases. In addition, higher levels of microbial exposure in infancy were associated with lower CRP. These associations were independent of socioeconomic status, measures of current body fat and other health behaviours. We conclude that measures of microbial exposure and nutrition during the pre-natal and early post-natal periods are important predictors of CRP concentration in young adulthood. We speculate that the development of anti-inflammatory regulatory networks in response to early microbial exposure represents plasticity in the development of anti-pathogen defences, and that this process may help explain the low CRP concentrations in this population.

Worldwide allele frequencies of the human apolipoprotein E gene: Climate, local adaptations, and evolutionary history

The epsilon4 allele of the apolipoprotein E (APOE) gene is associated with increased cholesterol levels and heart disease. Population allele frequencies of APOE have previously been shown to vary, with epsilon4 frequencies generally increasing with latitude. We hypothesize that this trend resulted from natural selection protecting against low-cholesterol levels. In high-latitude cold environments and low-latitude hot environments, metabolic rate is elevated, which could require higher cholesterol levels. To explore this hypothesis, we compiled APOE allele frequencies, latitude, temperature, and elevation from populations around the world. epsilon4 allele frequencies show a curvilinear relationship with absolute latitude, with lowest frequencies found in the mid-latitudes where temperatures generally require less expenditure on cooling/thermogenesis. Controlling for population structure in a subset of populations did not appreciably change this pattern of association, consistent with selection pressures that vary by latitude shaping epsilon4 allele frequencies. Temperature records also predict APOE frequency in a curvilinear fashion, with lowest epsilon4 frequencies at moderate temperatures. The model fit between historical temperatures and epsilon4 is less than between latitude and epsilon4, but strengthened after correcting for estimated temperature differences during the Paleolithic. Contrary to our hypothesis, we find that elevation did not improve predictive power, and an integrated measure of the cholesterol effect of multiple APOE alleles was less related to latitude than was epsilon4 alone. Our results lend mixed support for a link between past temperature and human APOE allele distribution and point to the need to develop better models of past climate in future analyses.

Size at Birth, Weight Gain in Infancy and Childhood, and Adult Diabetes Risk in Five Low- or Middle-Income Country Birth Cohorts

OBJECTIVE We examined associations of birth weight and weight gain in infancy and early childhood with type 2 diabetes (DM) risk in five cohorts from low- and middle-income countries. RESEARCH DESIGN AND METHODS Participants were 6,511 young adults from Brazil, Guatemala, India, the Philippines, and South Africa. Exposures were weight at birth, at 24 and 48 months, and adult weight, and conditional weight gain (CWG, deviation from expected weight gain) between these ages. Outcomes were adult fasting glucose, impaired fasting glucose or DM (IFG/DM), and insulin resistance homeostasis model assessment (IR-HOMA, three cohorts). RESULTS Birth weight was inversely associated with adult glucose and risk of IFG/DM (odds ratio 0.91[95% CI 0.84–0.99] per SD). Weight at 24 and 48 months and CWG 0–24 and 24–48 months were unrelated to glucose and IFG/DM; however, CWG 48 months–adulthood was positively related to IFG/DM (1.32 [1.22–1.43] per SD). After adjusting for adult waist circumference, birth weight, weight at 24 and 48 months and CWG 0–24 months were inversely associated with glucose and IFG/DM. Birth weight was unrelated to IR-HOMA, whereas greater CWG at 0–24 and 24–48 months and 48 months–adulthood predicted higher IR-HOMA (all P < 0.001). After adjusting for adult waist circumference, birth weight was inversely related to IR-HOMA. CONCLUSIONS Lower birth weight and accelerated weight gain after 48 months are risk factors for adult glucose intolerance. Accelerated weight gain between 0 and 24 months did not predict glucose intolerance but did predict higher insulin resistance.

Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants

Telomeres are repeating DNA sequences at the ends of chromosomes that protect and buffer genes from nucleotide loss as cells divide. Telomere length (TL) shortens with age in most proliferating tissues, limiting cell division and thereby contributing to senescence. However, TL increases with age in sperm, and, correspondingly, offspring of older fathers inherit longer telomeres. Using data and samples from a longitudinal study from the Philippines, we first replicate the finding that paternal age at birth is associated with longer TL in offspring (n = 2,023, P = 1.84 × 10−6). We then show that this association of paternal age with offspring TL is cumulative across multiple generations: in this sample, grandchildren of older paternal grandfathers at the birth of fathers have longer telomeres (n = 234, P = 0.038), independent of, and additive to, the association of their father’s age at birth with TL. The lengthening of telomeres predicted by each year that the father’s or grandfather’s reproduction are delayed is equal to the yearly shortening of TL seen in middle-age to elderly women in this sample, pointing to potentially important impacts on health and the pace of senescent decline in tissues and systems that are cell-replication dependent. This finding suggests a mechanism by which humans could extend late-life function as average age at reproduction is delayed within a lineage.