Strategically placed, our epithelium plays an essential role in maintaining and guarding tissue homeostasis. One key set of defense mechanisms is represented by our inflammasomes, which sense and respond to pathogen attack, through the secretion of pro-inflammatory cytokines. This review will focus on how the inflammasomes, our front-line warriors, maintain our skin, respiratory, and gut epithelial barrier immunity.

Our epithelium represents a battle ground against a variety of insults including pathogens and danger signals. It encodes multiple sensors that detect and respond to such insults, playing an essential role in maintaining and defending tissue homeostasis. One key set of defense mechanisms is our inflammasomes which drive innate immune responses including, sensing and responding to pathogen attack, through the secretion of pro-inflammatory cytokines and cell death. Identification of physiologically relevant triggers for inflammasomes has greatly influenced our ability to decipher the mechanisms behind inflammasome activation. Furthermore, identification of patient mutations within inflammasome components implicates their involvement in a range of epithelial diseases. This review will focus on exploring the roles of inflammasomes in epithelial immunity and cover: the diversity and differential expression of inflammasome sensors amongst our epithelial barriers, their ability to sense local infection and damage and the contribution of the inflammasomes to epithelial homeostasis and disease.

During aging, a progressive failure of energy metabolism occurs resulting in brain hypometabolism. This condition, combined with redox disturbance, contributes to increase neuronal cell vulnerability ultimately leading to neurodegeneration. Down syndrome and Alzheimer disease neuropathologies present several molecular similarities, among which perturbation of redox homeostasis and reduced energy production are major players that accelerate neuronal damage.

Redox reactions play a critical role for intracellular processes, including pathways involved in metabolism and signaling. Reactive oxygen species (ROS) act either as second messengers or generators of protein modifications, fundamental mechanisms for signal transduction. Disturbance of redox homeostasis is associated with many disorders. Among these, Alzheimer's disease is a neurodegenerative pathology that presents hallmarks of oxidative damage such as increased ROS production, decreased activity of antioxidant enzymes, oxidative modifications of macromolecules, and changes in mitochondrial homeostasis. Interestingly, alteration of redox homeostasis is closely associated with defects of energy metabolism, involving both carbohydrates and lipids, the major energy fuels for the cell. As the brain relies exclusively on glucose metabolism, defects of glucose utilization represent a harmful event for the brain. During aging, a progressive perturbation of energy metabolism occurs resulting in brain hypometabolism. This condition contributes to increase neuronal cell vulnerability ultimately resulting in cognitive impairment. The current review discusses the crosstalk between alteration of redox homeostasis and brain energy defects that seems to act in concert in promoting Alzheimer's neurodegeneration.

Here we review the aging of the hematopoietic system from its earliest stages in the embryo through fetal and adult life. We focus on the waves of hematopoietic cell generation during embryonic life and how cells of varying lineages, functions and life spans contribute to the normal development of the adult blood system and its progressive gain/loss of function in the aged adult.

Aging is a set of complex processes that occur temporally and continuously. It is generally a unidirectional progression of cellular and molecular changes occurring during the life stages of cells, tissues and ultimately the whole organism. In vertebrate organisms, this begins at conception from the first steps in blastocyst formation, gastrulation, germ layer differentiation, and organogenesis to a continuum of embryonic, fetal, adolescent, adult, and geriatric stages. Tales of the “fountain of youth” and songs of being “forever young” are dominant ideas informing us that growing old is something science should strive to counteract. Here, we discuss the normal life stages of the blood system, particularly the historical recognition of its importance in the early growth stages of vertebrates, and what this means with respect to progressive gain and loss of hematopoietic function in the adult.

CBX proteins are epigenetic reader proteins that can recognize histone modifications and thereby dictate cell fate. In this review, we describe how CBX proteins dictate cell fate in normal hematopoiesis and leukemia. In addition, we discuss which CBX proteins can promote leukemic cell growth and whether pharmacological inhibition of CBX proteins can reverse leukemic cell fate.

Hematopoietic stem cell (HSC) fate decisions are dictated by epigenetic landscapes. The Polycomb Repressive Complex 1 (PRC1) represses genes that induce differentiation, thereby maintaining HSC self-renewal. Depending on which chromobox (CBX) protein (CBX2, CBX4, CBX6, CBX7, or CBX8) is part of the PRC1 complex, HSC fate decisions differ. Here, we review how this occurs. We describe how CBX proteins dictate age-related changes in HSCs and stimulate oncogenic HSC fate decisions, either as canonical PRC1 members or by alternative interactions, including non-epigenetic regulation. CBX2, CBX7, and CBX8 enhance leukemia progression. To target, reprogram, and kill leukemic cells, we suggest and describe multiple therapeutic strategies to interfere with the epigenetic functions of oncogenic CBX proteins. Future studies should clarify to what extent the non-epigenetic function of cytoplasmic CBX proteins is important for normal, aged, and leukemic blood cells.