The Critical Role of Autophagy and Phagocytosis in the Aging Brain.

As the organism ages, there is a decline in effective energy supply, and this retards the ability to elaborate new proteins. The consequences of this are especially marked in the gradual decline in brain function. The senescence of cells and their constituent organelles is ultimately the cause of aging of the entire nervous system.

Mitochondrial Dysfunction as the Major Basis of Brain Aging.

The changes in the properties of three biological events that occur with cerebral aging are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs.

The Hormesis Concept: Strengths and Shortcomings.

Hormesis implies that the effects of various materials or conditions that organisms are exposed to, may not have linear dose-response characteristics but rather, can be biphasic. Thus the response to a low dose of a stressor may be the opposite to that occurring at higher doses. Such a dual response is postulated for many toxicants and physical conditions and may involve a beneficial adaptive response.

Melatonin and Aging.

The health problems associated with the aging process are becoming increasingly widespread due to the increase in mean life expectancy taking place globally. While decline of many organ functions is an unavoidable concomitant of senescence, these can be delayed or moderated by a range of factors. Among these are dietary changes and weight control, taking sufficient exercise, and the utilization of various micronutrients.

The Molecular Basis for the Environmental Promotion of Neurodegenerative Disease.

Most neurodegenerative diseases have a relatively minor genetic component [...

Relationships between Diabetes and the Intestinal Microbial Population.

Diabetes is a metabolic disorder characterized by lower responsiveness of tissues to insulin and consequent large variations in circulating levels of glucose. This fluctuation has harmful effects as both hyperglycemia and hypoglycemia can be very injurious. The causes of diabetes are varied but the consequences are rather uniform.

Electronic cigarette aerosol increases the risk of organ dysfunction by enhancing oxidative stress and inflammation.

An electronic cigarette is a rechargeable device that produces an inhaled aerosol containing varying levels of nicotine, and inorganic and organic toxicants and carcinogenic compounds. The aerosol is generated by heating a solution of propylene glycol and glycerin with nicotine and flavoring ingredients at a high temperature. The e-cigarette was developed and marketed as a safer alternative to the regular cigarette which is known to be injurious to human health.

Can a Micronutrient Mixture Delay the Onset and Progression of Symptoms of Single-Point Mutation Diseases?

Single-point mutation diseases in which substitution of one nucleotide with another in a gene occurs include familial Alzheimer's disease (fAD), familial Parkinson's disease (fPD), and familial Creutzfeldt-Jacob disease (fCJD) as well as Huntington's disease (HD), sickle cell anemia, and hemophilia. Inevitability of occurrence of these diseases is certain. However, the time of appearance of symptoms could be influenced by the diet, environment, and possibly other genetic factors.

Alternatives to Insulin for the Regulation of Blood Sugar Levels in Type 2 Diabetes.

This short overview focuses on the causation and treatment of type 2 diabetes (T2D). Emphasis is given to the historical basis of understanding this disease and the background leading to emergence of the central role of insulin. The strengths of insulin administration in the treatment of diabetes are profound, but these need to be balanced against several serious shortcomings of its extended use.

Attenuation of acute and chronic inflammation using compounds derived from plants.

The appearance of excessive inflammatory activity is associated with onset of many disease states. Such non-productive responses are often the basis of the mortality consequent to incurring numerous disorders. The current outbreak of coronavirus disease 2019 caused by the virus "severe acute respiratory syndrome coronavirus 2" is a striking reflection of the inadequacy of current medical science to adequately address this issue.

Melatonin and Regulation of Immune Function: Impact on Numerous Diseases.

Melatonin is well known as a neuroendocrine hormone that promotes sleep. However, the many other attributes of melatonin are less apparent and not as widely appreciated. The purpose of this review is to summarize the qualities of melatonin relating to immune function.

Distinctive cellular response to aluminum based adjuvants.

Aluminum-based adjuvants (ABAs) are used in human vaccines to enhance the magnitude of protective immune responses elicited against specific pathogens. One hypothesis is that stress signals released by aluminum-exposed necrotic cells play a role in modulating an immune response that contributes to the adjuvant's effectiveness. We hypothesized that aluminum adjuvant-induced necrosis would be similar irrespective of cellular origin or composition of the adjuvant.

Aspects of the immune system that impact brain function.

The conditions required for effective immune responses to viral or bacterial organisms and chemicals of exogenous origin and to intrinsic molecules of abnormal configuration, are briefly outlined. This is followed by a discussion of endocrine and environmental factors that can lead to excessive continuation of immune activity and persistent elevation of inflammatory responses. Such disproportionate activity becomes increasingly pronounced with aging and some possible reasons for this are considered.

Increased oxidative stress, inflammation, and glutamate: Potential preventive and therapeutic targets for hearing disorders.

Hearing disorders constitute one of the major health concerns in the USA. Decades of basic and clinical studies have identified numerous ototoxic agents and investigated their modes of action on the inner ear, utilizing tissue culture as well as animal and human models. Current preventive and therapeutic approaches are considered unsatisfactory.

Oxidative and Inflammatory Events in Prion Diseases: Can They Be Therapeutic Targets?

Prion diseases are a group of incurable infectious terminal neurodegenerative diseases caused by the aggregated misfolded PrPsc in selected mammals including humans. The complex physical interaction between normal prion protein PrPc and infectious PrPsc causes conformational change from the α- helix structure of PrPc to the β-sheet structure of PrPsc, and this process is repeated. Increased oxidative stress is one of the factors that facilitate the conversion of PrPc to PrPsc.

Dietary Fibers and Their Fermented Short-Chain Fatty Acids in Prevention of Human Diseases.

Many studies show that daily consumption of high-fiber diet is associated with a reduced risk of developing kidney stones, inflammatory disease, colon cancer and other malignancies, obesity, type II diabetes, and cardiovascular disease. Dietary fibers are non-digestible polysaccharides that are composed of complex carbohydrates. Based on their relative solubility in water, dietary fibers can be divided into insoluble and soluble forms.

Mechanisms Underlying Tumor Suppressive Properties of Melatonin.

There is considerable evidence that melatonin may be of use in the prevention and treatment of cancer. This manuscript will review some of the human, animal and cellular studies that provide evidence that melatonin has oncostatic properties. Confirmation that melatonin mitigates pathogenesis of cancer will be described from both direct study of its effects on carcinogenesis, and from indirect findings implicating disruption of the circadian cycle.

Environmental and Dietary Exposure to Copper and Its Cellular Mechanisms Linking to Alzheimer's Disease.

Metals are commonly found in the environment, household, and workplaces in various forms, and a significant segment of the population is routinely exposed to the trace amount of metals from variety of sources. Exposure to metals, such as aluminum, lead, iron, and copper, from environment has long been debated as a potential environmental risk factor for Alzheimer's disease (AD) for decades, yet results from in vitro, in vivo, and human population remain controversial. In the case of copper, the neurotoxic mechanism of action was classically viewed as its strong affinity to amyloid-beta (Aβ) to help its aggregation and increase oxidative stress via Fenton reaction.

Water Quality and Brain Function.

In the United States, regulations are in place to ensure the quality of drinking water. Such precautions are intended to safeguard the health of the population. However, regulatory guidelines may at times fail to achieve their purpose.

MicroRNAs in Hearing Disorders: Their Regulation by Oxidative Stress, Inflammation and Antioxidants.

MicroRNAs (miRs) are small non-coding single-stranded RNAs that bind to their complimentary sequences in the 3'-untranslated regions (3'-UTRs) of the target mRNAs that prevent their translation into the corresponding proteins. Since miRs are strongly expressed in cells of inner ear and play a role in regulating their differentiation, survival and function, alterations in their expression may be involved in the pathogenesis of hearing disorders. Although increased oxidative stress and inflammation are involved in initiation and progression of hearing disorders, it is unknown whether the mechanisms of damage produced by these biochemical events on inner ear cells are mediated by altering the expression of miRs.

Telomere shortening during aging: Attenuation by antioxidants and anti-inflammatory agents.

Telomeres are a repeated sequence -of bases found at the ends of chromosomes. In humans, this sequence is TTAGGG, which is repeated over 2000 times. Telomeres protect the ends chromosomes from fusion with nearby chromosomes, and allow effective replication of DNA.

Exposure to ambient ultrafine particulate matter alters the expression of genes in primary human neurons.

Exposure to ambient particulate matter (PM) has been associated with the onset of neurodevelopmental and neurodegenerative disorders, but the mechanism of toxicity remains unclear. To gain insight into this neurotoxicity, this study sought to examine global gene expression changes caused by exposure to ambient ultrafine PM. Microarray analysis was performed on primary human neurons derived from fetal brain tissue after a 24h exposure to 20μg/mL of ambient ultrafine particles.

Anthropogenic pollutants may increase the incidence of neurodegenerative disease in an aging population.

The current world population contains an ever-increasing increased proportion of the elderly. This is due to global improvements in medical care and access to such care. Thus, a growing incidence of age-related neurodegenerative disorders is to be expected.

Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration.

Aluminum (Al) is a very common component of the earth's mineral composition. It is not essential element for life and is a constituent of rather inert minerals. Therefore, it has often been regarded as not presenting a significant health hazard.