Journal of internal medicine
-
Sedentary lifestyle accelerates biological ageing, is a major risk factor for developing metabolic syndrome and is associated with cardiovascular disease, diabetes mellitus, kidney failure, sarcopenia and osteoporosis. In contrast to the linear path to worsening health in humans with metabolic syndrome, brown bears have developed a circular metabolic plasticity enabling these animals to tolerate obesity and a 'sedentary lifestyle' during hibernation and exit the den metabolically healthy in spring. Bears are close to humans physiology wise, much closer than rodents, the preferred experimental animals in medical research, and may better serve as translational model to develop treatments for lifestyle-related diseases. In this review, aspects of brown bear hibernation survival strategies are outlined and conceivable experimental strategies to learn from bears are described.
-
Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. ⋯ The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous-Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12-14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving 'burden of life style' diseases, including obesity, diabetes and high blood pressure.
-
Although frailty is known to be an important prognostic factor in heart failure (HF), HF risk-adjustment models do not incorporate frailty measures and the interplay between frailty, age and pharmacotherapy is unclear. ⋯ Although the HFRS reflects aspects of frailty that patient age and Charlson scores do not, the addition of the HFRS to standard risk prediction equations provides little additional information. Prescribing practices correlate more with patient age than frailty status.
-
A paradox of so-called developed countries is that, as the major historical causes of human mortality are eliminated or mitigated by medical progress, lifestyle-related diseases have become major killers. Furthermore, as lifespan is extended by the combined effects of modern medicine, health span is struggling to keep apace because of the burden of noncommunicable diseases linked to diet and sedentary lifestyle. ⋯ Here, we review the detailed mechanisms whereby the gut microbiome may modulate risk of diseases linked to sedentary lifestyle and ageing-related health loss. We focus on the comparative value of natural animal models such as hibernation for studying metabolic regulation and the challenge of extrapolating from animal models to processes that occur in human ageing.
-
Innate and adaptive immune responses are pivotal in atherosclerosis, but their association with early-stage atherosclerosis in humans is incompletely understood. In this regard, untreated children with familial hypercholesterolaemia may serve as a human model to investigate the effect of elevated low-density lipoprotein (LDL)-cholesterol. ⋯ FH children display higher PBMC expression of immune-related genes mapped to several pathways, including T and B cells, and TNFSF than healthy children. Our results suggest that LDL-C plays an important role in modulating expression of different immune-related genes, and novel data on the involvement of these pathways in the early atherosclerosis may represent future therapeutic targets for prevention of atherosclerotic progression.