Abstract:Aging has a profound and devastating effect on the brain. Old age is accompanied by declining cognitive function and enhanced risk of brain diseases, including cancer and neurodegenerative disorders. A key question is whether cells with regenerative potential contribute to brain health and even brain ''rejuvenation.'' This review discusses mechanisms that regulate neural stem cells (NSCs) during aging, focusing on the effect of metabolism, genetic regulation, and the surrounding niche. We also explore emerging… Show more
“…While a full description of the niche architecture and its influence on neurogenesis is beyond the scope of this review (see Bond et al., 2015 ), the niche is critical for supporting healthy neurogenesis. Disruptions to the neurogenic niche can lead to learning and memory impairments, whereas rejuvenation of the aged niche can rescue cognition ( Navarro Negredo et al., 2020 ).…”
Cognitive deficits associated with Alzheimer's disease (AD) severely impact daily life for the millions of affected individuals. Progressive memory impairment in AD patients is associated with degeneration of the hippocampus. The dentate gyrus of the hippocampus, a region critical for learning and memory functions, is a site of adult neurogenesis in mammals. Recent evidence in humans indicates that hippocampal neurogenesis likely persists throughout life, but declines with age and is strikingly impaired in AD. Our understanding of how neurogenesis supports learning and memory in healthy adults is only beginning to emerge. The extent to which decreased neurogenesis contributes to cognitive decline in aging and AD remains poorly understood. However, studies in rodent models of AD and other neurodegenerative diseases raise the possibility that targeting neurogenesis may ameliorate cognitive dysfunction in AD. Here, we review recent progress in understanding how adult neurogenesis is impacted in the context of aging and AD.
“…While a full description of the niche architecture and its influence on neurogenesis is beyond the scope of this review (see Bond et al., 2015 ), the niche is critical for supporting healthy neurogenesis. Disruptions to the neurogenic niche can lead to learning and memory impairments, whereas rejuvenation of the aged niche can rescue cognition ( Navarro Negredo et al., 2020 ).…”
Cognitive deficits associated with Alzheimer's disease (AD) severely impact daily life for the millions of affected individuals. Progressive memory impairment in AD patients is associated with degeneration of the hippocampus. The dentate gyrus of the hippocampus, a region critical for learning and memory functions, is a site of adult neurogenesis in mammals. Recent evidence in humans indicates that hippocampal neurogenesis likely persists throughout life, but declines with age and is strikingly impaired in AD. Our understanding of how neurogenesis supports learning and memory in healthy adults is only beginning to emerge. The extent to which decreased neurogenesis contributes to cognitive decline in aging and AD remains poorly understood. However, studies in rodent models of AD and other neurodegenerative diseases raise the possibility that targeting neurogenesis may ameliorate cognitive dysfunction in AD. Here, we review recent progress in understanding how adult neurogenesis is impacted in the context of aging and AD.
“…The adult brain contains regenerative neural stem cell (NSC) niches, with progenitors that can migrate to distal brain regions to generate new neurons and glial cells 1 . The regenerative potential of stem cell regions in the brain declines with age, and this is accompanied by a corresponding deterioration in aspects of sensory and cognitive function and in repair ability [2][3][4][5][6] .…”
Aging is accompanied by a deterioration in the regenerative and repair potential of stem cell regions in the brain. However, the mechanisms underlying this decline are largely unknown. Here we profile the chromatin landscape of five different cell types freshly isolated from the subventricular zone neurogenic niche of young and old mice. We find that chromatin states exhibit distinct changes with aging in different cell types. Notably, the chromatin of quiescent neural stem cells (NSCs) becomes more repressed with age whereas that of proliferative, activated NSCs becomes more open. Surprisingly, these opposing age-related chromatin changes involve cell adhesion and migration pathways. We experimentally validate that quiescent and activated NSCs exhibit opposite migratory deficits during aging. Quiescent NSCs become more migratory during aging, whereas activated NSCs and progeny become less migratory and less able to mobilize out of the niche in vivo during aging. The cellular mechanism by which aging impairs the migration of activated NSCs and progeny involves increased occurrence of force-producing focal adhesions. Inhibiting the cytoskeletal-regulating kinase ROCK in old activated NSCs and progenitors eliminates cell adhesive forces and boosts migration speed, reverting these cells to a more youthful migratory state. Our work has important implications for restoring the migratory potential of NSCs during aging and brain injury.
“…Adult neural stem cells (NSCs) in the mature nervous system are a common source of all nerve cells, including neurons, astrocytes, and oligodendrocytes (Navarro Negredo et al, 2020). Astrocytes excite inhibitory neurons and inhibit the general activities of peripheral neurons that prevent overexcitation of neurons in the nerve ring (Choe et al, 2012).…”
Section: Neuroprotective Properties Of Psoralenmentioning
Psoralen is the principal bioactive component in the dried fruits of Cullen corylifolium (L.) Medik (syn. Psoralea corylifolia L), termed "Buguzhi" in traditional Chinese medicine (TCM). Recent studies have demonstrated that psoralen displays multiple bioactive properties, beneficial for the treatment of osteoporosis, tumors, viruses, bacteria, and inflammation. The present review focuses on the research evidence relating to the properties of psoralen gathered over recent years. Firstly, multiple studies have demonstrated that psoralen exerts strong anti-osteoporotic effects via regulation of osteoblast/osteoclast/chondrocyte differentiation or activation due to the participation in multiple molecular mechanisms of the wnt/b-catenin, bone morphogenetic protein (BMP), inositol-requiring enzyme 1 (IRE1)/ apoptosis signaling kinase 1 (ASK1)/c-jun N-terminal kinase (JNK) and the Protein Kinase B (AKT)/activator protein-1 (AP-1) axis, and the expression of miR-488, peroxisome proliferators-activated receptor-gamma (PPARg), and matrix metalloproteinases (MMPs). In addition, the antitumor properties of psoralen are associated with the induction of ER stress-related cell death via enhancement of PERK: Pancreatic Endoplasmic Reticulum Kinase (PERK)/activating transcription factor (ATF), 78kD glucose-regulated protein (GRP78)/C/EBP homologous protein (CHOP), and 94kD glucose-regulated protein (GRP94)/CHOP signaling, and inhibition of P-glycoprotein (P-gp) or ATPase that overcomes multidrug resistance. Furthermore, multiple articles have shown that the antibacterial, anti-inflammatory and neuroprotective effects of psoralen are a result of its interaction with viral polymerase (Pol), destroying the formation of biofilm, and regulating the activation of tumor necrosis factor alpha (TNF-a), transforming growth factor beta (TGF-b), interleukin 4
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