BACKGROUND: Zinc deficiency due to poor nutrition or genetic mutations in zinc transporters is a global health problem and approaches to providing effective dietary zinc supplementation while avoiding potential toxic side effects are needed. METHODS/PRINCIPAL FINDINGS: Conditional knockout of the intestinal zinc transporter Zip4 (Slc39a4) in mice creates a model of the lethal human genetic disease acrodermatitis enteropathica (AE).
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in superoxide dismutase (SOD1) are associated with familial ALS and lead to SOD1 protein misfolding and aggregation. Here we show that the molecular chaperone, HSJ1 (DNAJB2), mutations in which cause distal hereditary motor neuropathy, can reduce mutant SOD1 aggregation and improve motor neuron survival in mutant SOD1 models of ALS.
Alloantibody can be a major barrier to successful organ transplantation; however, therapy to control antibody production or to alter its impact on the allograft remains limited. The goal of this review is to examine the regulatory steps that are involved in the generation of alloreactive B cells, with a specific emphasis on how known mechanisms relate to clinical situations in transplant recipients. Thus, we will examine the process of activation of mature, naÔve B cells and how this relates to de novo antibody production.
Emerging lines of evidence suggest a relationship between amyotrophic lateral sclerosis (ALS) and protein sumoylation. Multiple studies have demonstrated that several of the proteins involved in the pathogenesis of ALS, including superoxide dismutase 1, fused in liposarcoma, and TAR DNA-binding protein 43 (TDP-43), are substrates for sumoylation.
Dietary manipulation may influence outcome after infection and injury by altering production of inflammatory mediators and disease activity. Restricted nutrient intake may have beneficial effects on life-span, development of degenerative disease, autoimmune processes, renal injury, susceptibility to infection, and survival rate after infection. Nutritional therapies that serve to maximize nitrogen balance may adversely affect the host response to injury, especially when given in excess of energy and protein needs.
The epidemiological links observed between fetal and infant growth and impaired glucose tolerance in adult life that led to the formulation of the "thrifty phenotype" hypothesis have been confirmed by others in widely differing populations. The proposed nutritional basis of these links has been tested in an animal model in which rat dams were fed an isocaloric low-protein diet and the postweaning normally fed offspring were studied.
Dietary caloric restriction is the most robust and reproducible means of slowing aging and extending lifespan and healthspan in short-lived mammals and lower organisms. Numerous aspects of this paradigm have been investigated in laboratories around the world since its inception more than 60 years ago. However, two questions about calorie restriction remain unanswered to this day: (1) By what mechanism does it work? and (2) Will it work in humans?
The question of whether temporal equivalence can be established between test species and humans and be useful in the safety assessment of food additives has puzzled risk assessors throughout decades. The basic biological elements in any mammalian species, including humans, such as homeostasis, basal metabolism and body size/surface area, reproduction features, the timing of cellular proliferation, and aging and health as well as the relation between aging and the diet are essential in this discussion.
The present study is part of a larger project that investigates the effect of caloric restriction on longevity in the rhesus monkey. The purpose of the present study was to document presbycusis and the effect of caloric restriction on presbycusis in monkeys. The control group had 35 monkeys allowed to eat freely and the caloric-restricted group (CR) had 33 monkeys with a 30% reduction in caloric intake.
Can mouse genetics teach us enough about the biology of aging to guide the search for anti-aging medicines that can delay late-life illness? Recent progress gives reason for optimism, with new data showing that changes in single genes can extend average and maximal life span by 40%. Mice with these genetic variants remain healthy, active, and cognitively intact at average ages that correspond to 110-120 years of human life span.