Kuzawa Group: Research Overview

Our interests broadly span developmental and intergenerational biology, epigenetics, health inequality, the biology of reproduction, the energetic costs and health impacts of human brain development, the history and misuse of the race concept, and the psychobiology of social relationships. Since 1998, the group has worked closely with colleagues at the Office of Population Studies in Cebu, Philippines, on the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The CLHNS is a longitudinal birth cohort located in metropolitan Cebu, Philippines, that enrolled more than 3,000 pregnant women in 1983 and has since followed them, their offspring, and now their grandoffspring for 40 years. Our group, along with students and collaborators, uses these data to explore a wide array of questions, including the long-term impacts of early environments on cardiovascular disease, aging, reproduction, and immunity; the intergenerational determinants of telomere length; and the intergenerational impacts of early-life nutritional stress on epigenetics and offspring birth outcomes. Current and former students and postdocs in the group have explored these general themes not only in Cebu, but also in New Zealand, South Africa, Mexico, Cameroon, Cuba, and the United States including Alaska.

Developmental and Intergenerational Origins of Adult Health

Many biological systems have brief periods of heightened environmental sensitivity that overlap with the age of dependence on resources or hormones transferred across the placenta or via breast milk. These windows of developmental plasticity, and their sensitivity to maternal cues, open channels for transferring non-genetic information between generations (maternal effects). At Cebu, the Kuzawa group and its collaborators and students have clarified the early-life predictors of a range of metabolic, reproductive, and immune functions. The group focuses not only on clarifying the long-term impacts of early environments on biology and health, but also looks back in time to ask what in the mother's experience — nutrition, stress, health — shapes the resources or cues she conveys across generations, helping establish offspring developmental trajectories.

The Energetic Costs of Human Brain Development: Implications for Human Life History and Public Health

In a highly cited statistic, the human brain accounts for 2% of body weight but, despite this, uses 20% of the body's energy at rest. During infancy and childhood, the brain is especially large relative to body size, implying that it requires an even larger portion of the body's energy pool at these ages. Using PET and MRI data, the Kuzawa group and collaborators showed that the fraction of the body's resting metabolic rate devoted to the brain is 50% at birth, drops to 35% by 6 months, then rises to a lifetime peak of 66% of RMR at 4 years of age, reflecting the high energetic costs of synaptogenesis. The group further showed that brain energetics and body-weight growth rate are tightly, linearly, inversely correlated, establishing that the high costs of brain development help explain our species' unusually slow and protracted period of childhood growth. These findings also highlight the likely importance of humans' uniquely high brain costs (which rely primarily on glucose) to the developmental etiology of obesity and diabetes. As one example, the age of peak brain energetics coincides with the timing of the adiposity rebound — the age of slowest growth and lowest body fat stores in childhood. Because the timing of the adiposity rebound predicts long-term body composition trajectories, this work points to an important role for variation in brain energetics — the timing and height of peak brain expenditure — in lifelong body composition trajectories.

Debunking the Concept of Genetic Race

Early models of human race wrongly evoked simplistic renderings of evolutionary theory to argue for the inherent superiority of specific populations. Today, debates about the biological bases and causes of human diversity play out primarily within public health and medicine, which grapple with explaining the relative importance of genetic and environmental contributions to health disparities. Environment-driven developmental plasticity and epigenetic change help explain why phenotypes map onto the gradients of environmental stress and opportunity that societies organize around social categories such as race or class. The Kuzawa group applies principles of developmental plasticity and epigenetics to help update understandings of the origins of modern human biological diversity and related health disparities. Current and former students address these themes in work in New Zealand, South Africa, Mexico, Cameroon, Cuba, and the United States (including Alaska). The group also engages in interdisciplinary collaborations with historians of science and science and technology studies scholars to interrogate the early history of the race concept and the lessons it may offer for current developments in fields like epigenetics and DOHaD.

Human Life History Evolution and Reproductive Ecology

Hallmarks of the human life cycle include early weaning and a fertility rate unusually high for a large-bodied, high-investment primate, which requires a flexible social network of offspring provisioning and care to sustain. Past research in birds in which males provide care shows that testosterone is often reduced as males become fathers and their priorities shift. Consistent with this model, work by the Kuzawa group at Cebu was the first to use longitudinal data to show that men experience a dramatic decline in testosterone as they transition into new fatherhood (see NY Times coverage here). Because no similar effects are seen in other closely related primates (or in most mammals), this work suggests that paternal care of offspring has likely been sufficiently important to human reproductive success to favor the evolution of male capacities to adjust hormones and priorities as men enter culturally defined fathering roles. Under the leadership of former PhD advisee Lee Gettler (now Professor and Department Chair at Notre Dame), along with former postdoc Stacy Rosenbaum (now Associate Professor of Anthropology at Michigan), the group has explored multiple dimensions of human life history and reproductive strategy at Cebu, including the plasticity of life history strategies, endocrine correlates of caregiving, the social and familial predictors of cooperative care, and tests of models of maturational acceleration in response to cues of mortality and environmental harshness.

The Epigenetics of Aging

The recent development of epigenetic "clocks" is creating new opportunities to understand why individuals vary in the pace of health and functional decline with age. The Kuzawa group and its collaborators in the Philippines are nearing completion of a 5-year study that is recontacting cohort members and their mothers to update key survey information, obtain biological samples for epigenetic and biomarker assessment, and update mortality information. These data, along with the 40+ years of longitudinal data available for each birth cohort member, will help clarify the role of early-life factors as predictors of epigenetic age in early adulthood, and the lifestyle and other factors that influence the pace of change in epigenetic age across a 17-year period of follow-up. Data on these generations is thus allowing the group to study the aging process from birth through old-age decline and mortality, focusing on both the developmental and lifelong determinants of epigenetic age and the aging-related outcomes that epigenetic age predicts late in life.

Contact Chris Kuzawa if you are interested in joining our group as a postdoc, PhD student, or Harvard undergraduate.