The purpose of this Research Topic is to discuss the latest developments in aging and neurodegenerative diseases. Aging represents the major risk factor of the two most relevant neurodegenerative diseases Parkinson’s disease (PD) and Alzheimer’s disease (AD). It is generally accepted that symptoms of PD correlate with the severity of degeneration of dopaminergic substantia nigra neurons. In most cases neuronal loss during aging is not sufficient to cause clinical symptoms but only leads to a preclinical state of PD. However, in a small number of our population, neurodegeneration by aging gets accelerated by individual (e.g. brain injuries), environmental (e.g. toxins) and genetic (e.g. mutations of the alpha-synuclein gene) factors to reach the critical threshold for clinical symptoms during lifetime. Thus, neurodegeneration in PD appears to represent the common final pathway of “normal brain aging” and all other risk factors including genetics and the accumulation of the neurotoxic alpha-synuclein protein. While aging alone is generally agreed to be sufficient for at least the preclinical state of PD, the situation in AD seems to be different. Aging as the major and well documented risk factor of AD has been neglected for decades. Biochemical mechanisms of brain aging and the cognitive deficits of “normal brain aging” were seen as two not related and independent processes not related to AD. AD has always been characterized for decades by the presence of histopathological alterations (extracellular amyloid- containing plaques and intracellular tangles of hyperphosphorylated tau-protein), by neurodegeneration (synaptic deficits and finally neuronal loss), as well as by severe cognitive deficits clinically often accompanied by neuropsychiatric symptoms like delusions, as already described in the first famous patient Auguste D at the Psychiatric Hospital of Frankfurt. If or if not one or both of the two histopathological hallmarks play a causative role remains unclear until now. The discovery of homocygotic risk genes in most of the very rare (probably less than 1%) cases of early onset AD which share increased production of β-amyloid (Aβ) as one (but probably not the only one) common property led to the hypothesis of Aβ as the major causative factor for the development of AD. It was neglected that plaques density in the brain of AD patients did not correlate with presence and severity of clinical symptoms, while synaptic deficits did so even in first observations already published many years ago. Based on the Amyloid hypothesis, many drug treatments to remove Aβ plaques were developed. Even if all seemed to remove Aβ to some extent, all strategies failed to improve the symptoms of dementia. Thus, other concepts to explain the development of clinical symptoms of AD over time are needed. These should include the brain aging process not only as a statistical but also as a causative contributing factor. These concepts should not only relay on cell or animal models but should much more take into account the disease and the patients. A closer look at the situation in PD will certainly be helpful.

Impairment of energy metabolism is a hallmark of brain aging and several neurodegenerative diseases, such as the Alzheimer’s disease (AD). Age- and disease-related hypometabolism is commonly associated with oxidative stress and they are both regarded as major contributors to the decline in synaptic plasticity and cognition. Neuroinflammatory changes, entailing microglial activation and elevated expression of inflammatory cytokines, also correlate with age-related cognitive decline. It is still under debate whether the mitochondrial dysfunction-induced metabolic deficits or the microglia activation-mediated neuroinflammation is the initiator of the cognitive changes in aging and AD. Nevertheless, multiple lines of evidence support the notion that mitochondrial dysfunction and chronic inflammation exacerbate each other, and these mechanistic diversities have cellular redox dysregulation as a common denominator. This research topic focuses on the role of a metabolic-inflammatory axis encompassing the bioenergetic activity, brain inflammatory responses and their redox regulation in healthy brain aging and neurodegenerative diseases. Dynamic interactions among these systems are reviewed in terms of their causative or in-tandem occurrence and how the systemic environment, –e.g., insulin resistance, diabetes, and systemic inflammation–, impacts on brain function.

The 4th World Congress on Genetics, Geriatrics and Neurodegenerative Diseases Research (GeNeDis 2020) focuses on the latest major challenges in scientific research, new drug targets, the development of novel biomarkers, new imaging techniques, novel protocols for early diagnosis of neurodegenerative diseases, and several other scientific advances, with the aim of better, safer, and healthier aging. The increase in the average length of life leads to the development of various diseases in the elderly population. This volume focuses on the sessions from the conference on Geriatrics.

The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography

Recent studies have indicated that epigenetic processes may play a major role in both cellular and organismal aging. These epigenetic processes include not only DNA methylation and histone modifications, but also extend to many other epigenetic mediators such as the polycomb group proteins, chromosomal position effects, and noncoding RNA. The topics of this book range from fundamental changes in DNA methylation in aging to the most recent research on intervention into epigenetic modifications to modulate the aging process. The major topics of epigenetics and aging covered in this book are: 1) DNA methylation and histone modifications in aging; 2) Other epigenetic processes and aging; 3) Impact of epigenetics on aging; 4) Epigenetics of age-related diseases; 5) Epigenetic interventions and aging: and 6) Future directions in epigenetic aging research. The most studied of epigenetic processes, DNA methylation, has been associated with cellular aging and aging of organisms for many years. It is now apparent that both global and gene-specific alterations occur not only in DNA methylation during aging, but also in several histone alterations. Many epigenetic alterations can have an impact on aging processes such as stem cell aging, control of telomerase, modifications of telomeres, and epigenetic drift can impact the aging process as evident in the recent studies of aging monozygotic twins. Numerous age-related diseases are affected by epigenetic mechanisms. For example, recent studies have shown that DNA methylation is altered in Alzheimer’s disease and autoimmunity. Other prevalent diseases that have been associated with age-related epigenetic changes include cancer and diabetes. Paternal age and epigenetic changes appear to have an effect on schizophrenia and epigenetic silencing has been associated with several of the progeroid syndromes of premature aging. Moreover, the impact of dietary or drug intervention into epigenetic processes as they affect normal aging or age-related diseases is becoming increasingly feasible.

This Volume of the series Cardiac and Vascular Biology offers a comprehensive and exciting, state-of-the-art work on the current options and potentials of cardiac regeneration and repair. Several techniques and approaches have been developed for heart failure repair: direct injection of cells, programming of scar tissue into functional myocardium, and tissue-engineered heart muscle support. The book introduces the rationale for these different approaches in cell-based heart regeneration and discusses the most important considerations for clinical translation. Expert authors discuss when, why, and how heart muscle can be salvaged. The book represents a valuable resource for stem cell researchers, cardiologists, bioengineers, and biomedical scientists studying cardiac function and regeneration.

Exposure to toxic chemicalsâ€"in the workplace and at homeâ€"is increasing every day. Human behavior can be affected by such exposure and can give important clues that a person or population is in danger. If we can understand the mechanisms of these changes, we can develop better ways of testing for toxic chemical exposure and, most important, better prevention programs. This volume explores the emerging field of neurobehavioral toxicology and the potential of behavior studies as a noninvasive and economical means for risk assessment and monitoring. Pioneers in this field explore its promise for detecting environmental toxins, protecting us from exposure, and treating those who are exposed.