Journal of Internal Medicine最新文献

Although research on ageing has largely concentrated on understanding the fundamental biology of the ageing process and devising pharmaceutical interventions in order to slow it down, increasing evidence has underscored the crucial role of environmental inputs across the life course and across generations, in shaping both individual and intergenerational trajectories of age-related health. These include nutrition, air pollution, social deprivation, lifestyle factors, climate change and exposure to environmental toxins, including microplastics and nanoplastics. The development of the concept of the exposome of ageing and the emergence of the new field of ‘exposomics’ have identified a blind spot, in particular, for geroscience. The impact of the exposome affecting human ‘healthspan’ (i.e., years lived in good health), extending across generations, is significant and yet under-explored in research. As such, it is under-appreciated that the declining health of the planet will have intergenerational ripple effects, epigenetically priming adverse health in future generations. We discuss the capacity to manipulate our exposome to mitigate against such effects, by addressing root causes, rather than symptoms, of both physiological and planetary dysregulation, dysfunction and decay. We propose a systems-based framework that reconnects research on ageing with exposomics and planetary ecology, creating a new field of ‘ecological or exposome pharmacology’, harnessing the activity of Nrf2 as a senotherapeutic intervention to improve trans- and intergenerational physiology in the face of declining planetary health.

Background: Elevated low-density lipoprotein (LDL) cholesterol causes atherosclerotic cardiovascular diseases. Variables of whole-body cholesterol metabolism, for example, high cholesterol absorption efficiency, might also be atherogenic, whereas the role of bile acids is controversial.

Objectives: This post hoc study concerns the impact of cholesterol absorption on bile acid metabolism. The hypothesis was that cholesterol absorption efficiency interferes with bile acid metabolism.

Methods: Cholesterol metabolism was studied using absolute and relative methods. Elimination of cholesterol from the body as bile acids and neutral sterols was assessed from 24-h faecal collections and analysed by gas-liquid chromatography. Cholesterol absorption efficiency was evaluated by a peroral continuous dual-isotope feeding method, and cholesterol synthesis by a sterol-balance technique. The relative methods included analyses of serum biomarkers of cholesterol absorption efficiency and cholesterol synthesis by gas-liquid chromatography.

Results: Faecal bile acids, neutral sterols and cholesterol synthesis were lower in high- versus low-cholesterol absorbers. Elimination of cholesterol from the body as bile acids and neutral sterols was reduced in high- versus low-cholesterol absorbers. Serum and LDL cholesterol levels did not differ in low- versus high-cholesterol absorbers. Absolute and relative methods of cholesterol metabolism correlated with each other, suggesting that the results can be considered valid.

Conclusion: In high-cholesterol absorbers, poor elimination of cholesterol from the body as bile acids and neutral sterols may indicate an increased risk of atherosclerosis. It can be prevented by decreasing cholesterol absorption and increasing reverse cholesterol transport by dietary means combined with ezetimibe and statin treatment, when needed.

In this article, we present the state-of-the-art on socioeconomic health inequalities with a focus on the Nordic countries. Health inequalities have increased over time and can be observed for both mortality and morbidity. We show that cross-national comparisons reveal surprisingly high inequalities in the Nordic countries. It is now well established that health and mortality inequalities prevail also at older ages. We show, with data from Sweden, that the interpretation of how mortality inequalities evolve over the life course is markedly different depending on whether we focus on absolute or relative inequalities. Although there is a consensus on basic descriptive facts, disagreements on how these facts are best explained and why they persist and even increase remain. We present a general discussion on how to explain health inequalities, as well as a discussion on why patterns may differ between European regions and across the life course. We introduce a framework for understanding health inequalities, fundamental cause theory and discuss to what extent the evidence aligns with the theory. We review contemporary discussions on health inequalities in light of recent evidence based on novel methods for causal inference. We argue that health inequalities have important ramifications for population health regardless of whether they are primarily shaped by social causation or social selection and end by noting that as modern societies aspire to become more meritocratic, it is possible that socioeconomic position becomes increasingly important for health.