The future of evolutionary medicine: sparking innovation in biomedicine and public health.

Evolutionary medicine - i.e. the application of insights from evolution and ecology to biomedicine - has tremendous untapped potential to spark transformational innovation in biomedical research, clinical care and public health.

Anthropocene-related disease: The inevitable outcome of progressive niche modification?

While the Anthropocene is often discussed in terms of the health of the planet, there has been less attention paid to its impact on the health of humans. We argue that there is now sufficient evidence of broad and growing adverse effects on human health to consider Anthropocene-related diseases and their impact on public health as a category of conditions needing specific recognition and preventative action. Using the examples of climate change-related health challenges, non-communicable disease, antimicrobial resistance and the unique challenges of the digital environment, we discuss how the profound and pervasive environmental changes of the Anthropocene can affect our health, with broad effects on societal health.

Maternal and child health: is making 'healthy choices' an oxymoron?

The right to exercise choice is fundamental to the Universal Declaration of Human Rights, and it is assumed that all individuals generally enjoy freedom of choice in managing their health. Yet closer examination of this assumption calls into question its credibility and validity, especially with regard to maternal and child health around the globe. We argue that the concept of individual 'healthy choice,' particularly as applied to those with inadequate support and who are relatively disempowered, is flawed and unhelpful when considering the wider social, economic, and political forces underlying poor health.

Niche Modification, Human Cultural Evolution and the Anthropocene.

Niche-constructing organisms actively modify their environments with adaptive consequences, sustaining a new equilibrium. Modern humans are instead niche modifiers, continually changing their environments irrespective of adaptive pressures. The nature, scale, and speed of such modifications have potential ill effects that need to be addressed with multilevel societal initiatives.

Evolutionary and developmental mismatches are consequences of adaptive developmental plasticity in humans and have implications for later disease risk.

A discrepancy between the phenotype of an individual and that which would confer optimal responses in terms of fitness in an environment is termed 'mismatch'. Phenotype results from developmental plasticity, conditioned partly by evolutionary history of the species and partly by aspects of the developmental environment. We discuss two categories of such mismatch with reference primarily to nutrition and in the context of evolutionary medicine.

Interactions between peroxiredoxin 2, hemichrome and the erythrocyte membrane.

Peroxiredoxin 2 (Prx2) is an abundant antioxidant protein in erythrocytes that protects against hemolytic anemia resulting from hemoglobin oxidation and Heinz body formation. A small fraction of Prx2 is bound to the cell membrane, but the mechanism and relevance of binding are not clear. We have investigated Prx2 interactions with the erythrocyte membrane and oxidized hemoglobin and whether these interactions are dependent on Prx2 redox state.

Human growth: evolutionary and life history perspectives.

Evolutionary and life history perspectives allow a fuller understanding of both patterns of growth and development and variations in disease risk. Evolutionary processes act to ensure successful reproduction and not the preservation of health and longevity, and this entails trade-offs both between traits and across the life course. Developmental plasticity adjusts the developmental trajectory so that the phenotype in childhood and through peak reproduction will suit predicted environmental conditions - a capacity that may become maladaptive should early-life predictions be inaccurate.

Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments.

Epigenetic epidemiology: the rebirth of soft inheritance.

Non-communicable diseases (NCDs), such as cardiovascular disease and type 2 diabetes, constitute the main cause of death worldwide. Eighty percent of these deaths occur in low- and middle-income countries, especially as these countries undergo socio-economic improvement following reductions in the burden of infectious disease. The World Health Organization predicts a substantial increase in the incidence of NCDs over the next decade globally.

The role of developmental plasticity and epigenetics in human health.

Considerable epidemiological, experimental and clinical data have amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. This relationship reflects plastic responses made by the developing organism as an evolved strategy to cope with immediate or predicted circumstances, to maximize fitness in the context of the range of environments potentially faced. There is now increasing evidence, both in animals and humans, that such developmental plasticity is mediated in part by epigenetic mechanisms.

How evolutionary principles improve the understanding of human health and disease.

An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved.

Epigenetic mechanisms that underpin metabolic and cardiovascular diseases.

Cellular commitment to a specific lineage is controlled by differential silencing of genes, which in turn depends on epigenetic processes such as DNA methylation and histone modification. During early embryogenesis, the mammalian genome is 'wiped clean' of most epigenetic modifications, which are progressively re-established during embryonic development. Thus, the epigenome of each mature cellular lineage carries the record of its developmental history.

Peroxiredoxin 2 and peroxide metabolism in the erythrocyte.

Peroxiredoxin 2 (Prx2) is an antioxidant enzyme that uses cysteine residues to decompose peroxides. Prx2 is the third most abundant protein in erythrocytes, and competes effectively with catalase and glutathione peroxidase to scavenge low levels of hydrogen peroxide, including that derived from hemoglobin autoxidation. Low thioredoxin reductase activity in the erythrocyte is able to keep up with this basal oxidation and maintain the Prx2 in its reduced form, but exposure to exogenous hydrogen peroxide causes accumulation of the disulfide-linked dimer.

The high reactivity of peroxiredoxin 2 with H(2)O(2) is not reflected in its reaction with other oxidants and thiol reagents.

Peroxiredoxin 2 is a member of the mammalian peroxiredoxin family of thiol proteins that is important in antioxidant defense and redox signaling. We have examined its reactivity with various biological oxidants, in order to assess its ability to act as a direct physiological target for these species. Human erythrocyte peroxiredoxin 2 was oxidized stoichiometrically to its disulfide-bonded homodimer by hydrogen peroxide, as monitored electrophoretically under nonreducing conditions.

Peroxiredoxin 2 functions as a noncatalytic scavenger of low-level hydrogen peroxide in the erythrocyte.

Peroxiredoxin 2 (Prx2), a thiol-dependent peroxidase, is the third most abundant protein in the erythrocyte, and its absence in knock-out mice gives rise to hemolytic anemia. We have found that in human erythrocytes, Prx2 was extremely sensitive to oxidation by H(2)O(2), as dimerization was observed after exposure of 5 x 10(6) cells/mL to 0.5 muM H(2)O(2).