Nevertheless, these concepts prove insufficient to fully clarify the unusual age-related variation in migraine incidence. While the genesis of migraine is undeniably intertwined with the molecular/cellular and social/cognitive processes of aging, it simultaneously remains opaque in its selective manifestation in certain individuals, failing to pinpoint any direct causal relationship. The present narrative/hypothesis review explores the interrelationships between migraine and aging, specifically chronological aging, brain aging, cellular senescence, stem cell exhaustion, and the social, cognitive, epigenetic, and metabolic pathways of aging. We also point out the influence of oxidative stress in these interrelationships. Migraine, we hypothesize, is limited to those individuals who exhibit inherent, genetic/epigenetic, or acquired (through traumatic events, shocks, or complex emotional states) migraine predispositions. Individuals' predisposition to migraines, while somewhat age-related, shows a higher vulnerability to migraine triggers than in others. Aging's diverse triggers for migraine might disproportionately impact social aspects of aging. The prevalence of stress related to social aging reflects a similar age dependency as the prevalence of migraine itself. In addition, social aging displayed an association with oxidative stress, a critical component in multiple dimensions of aging. From a different angle, the molecular processes underlying social aging, in relation to migraine predisposition and sex-based prevalence differences, deserve further investigation and association with migraine.
Interleukin-11 (IL-11), a cytokine, contributes to the complex interplay of hematopoiesis, the progression of cancer metastasis, and inflammatory responses. IL-11, a cytokine related to IL-6, binds to a receptor system composed of the glycoprotein gp130 and the specific IL-11 receptor, or its soluble version, sIL-11R. Enhanced osteoblast differentiation and bone growth, coupled with a reduction in osteoclast-driven bone resorption and cancer bone metastasis, are observed in response to IL-11/IL-11R signaling. Recent studies have found that a deficiency in IL-11, affecting both systemic levels and osteoblasts/osteocytes, leads to lower bone mass and formation, and simultaneously promotes increased adiposity, reduced glucose tolerance, and insulin resistance. The occurrence of height reduction, osteoarthritis, and craniosynostosis in humans is associated with mutations in the genes IL-11 and IL-11RA. This review investigates the rising influence of IL-11/IL-11R signaling in bone turnover, highlighting its modulation of osteoblasts, osteoclasts, osteocytes, and the intricacies of bone mineralization. Furthermore, the influence of IL-11 extends to both stimulating osteogenesis and suppressing adipogenesis, consequently directing the differentiation pathway of osteoblasts and adipocytes derived from pluripotent mesenchymal stem cells. IL-11, a newly discovered bone-derived cytokine, plays a crucial role in mediating bone metabolism and the relationship between bone and other organs. In this regard, IL-11 is critical for the maintenance of bone and represents a possible therapeutic application.
Aging is fundamentally described by impaired physiological integrity, diminished organ and system function, greater susceptibility to environmental stressors, and the rise in various diseases. phytoremediation efficiency Our skin, the body's largest organ, may develop increased vulnerability to injury over time, manifesting as aged skin. A systematic review of three categories, encompassing seven hallmarks of skin aging, was undertaken here. Among these hallmarks, genomic instability and telomere attrition, epigenetic alterations and loss of proteostasis, deregulated nutrient-sensing, mitochondrial damage and dysfunction, cellular senescence, stem cell exhaustion/dysregulation, and altered intercellular communication are integral. The seven hallmarks of skin aging are organized into three categories: (i) primary hallmarks, emphasizing the root causes of skin damage; (ii) antagonistic hallmarks, focusing on the responses to this damage; and (iii) integrative hallmarks, encapsulating the causative factors that create the aging phenotype.
Huntington's disease (HD) is a neurodegenerative disorder emerging in adulthood, resulting from a trinucleotide CAG repeat expansion within the HTT gene, which encodes the huntingtin protein (HTT in humans, Htt in mice). Fundamental to both embryonic survival, normal neurogenesis, and adult brain function, HTT is a multi-functional and ubiquitous protein. Wild-type HTT's ability to defend neurons against various forms of cell death potentially implies that a deficiency in its normal function might intensify disease progression in HD. Clinical trials are focusing on Huntington's disease (HD) therapies that aim to decrease huntingtin levels, but some express anxieties about the possible negative ramifications of reducing wild-type HTT levels. We show that Htt levels are a factor in the occurrence of an idiopathic seizure disorder, which arises spontaneously in approximately 28% of FVB/N mice, a condition we have labeled FVB/N Seizure Disorder with SUDEP (FSDS). Hepatitis B chronic These abnormal FVB/N mice, representing a model of epilepsy, demonstrate the critical signs of spontaneous seizures, astrogliosis, neuronal hypertrophy, increased expression of brain-derived neurotrophic factor (BDNF), and abrupt seizure-related death. Intriguingly, mice that inherit one mutated copy of the Htt gene (Htt+/- mice) manifest an increased occurrence of this disorder (71% FSDS phenotype), whereas expressing either the whole wild-type HTT gene in YAC18 mice or the whole mutant HTT gene in YAC128 mice altogether prevents its manifestation (0% FSDS phenotype). The mechanism by which huntingtin modulates the frequency of this seizure disorder was examined, and the findings indicated that over-expression of the full-length HTT protein can promote neuronal survival after seizures occur. Our results strongly suggest a protective effect of huntingtin in this epilepsy, thus providing a plausible explanation for the seizures seen in juvenile Huntington's disease, Lopes-Maciel-Rodan syndrome, and Wolf-Hirschhorn syndrome. The implications of decreasing huntingtin levels for the treatment of Huntington's Disease necessitate a careful evaluation of the adverse outcomes for huntingtin-lowering therapies.
Endovascular therapy is the initial therapeutic approach for patients experiencing acute ischemic stroke. DNA Damage inhibitor However, studies have indicated that, despite the timely re-opening of occluded blood vessels, almost half of all patients receiving endovascular therapy for acute ischemic stroke still manifest poor functional recovery, a phenomenon termed futile recanalization. The pathophysiology of unsuccessful artery reopening is multifaceted and potentially includes the lack of restored blood flow to the tissues despite reopening the blocked main artery (tissue no-reflow), the blockage of the reopened artery shortly after treatment (early arterial re-occlusion), poor collateral circulation, cerebral bleeding following the initial stroke (hemorrhagic transformation), compromised blood flow self-regulation in the brain's blood vessels, and a considerable zone of insufficient blood supply. Therapeutic strategies aimed at these mechanisms have been tested in preclinical settings, but their clinical utility has yet to be established. Focusing on the pathophysiology and targeted therapies of no-reflow, this review summarizes the risk factors, mechanisms, and treatment strategies of futile recanalization. Its goal is to expand our understanding of this phenomenon and suggest new translational research ideas and potential intervention targets for improving endovascular therapy's effectiveness in acute ischemic stroke.
Recent decades have witnessed a surge in gut microbiome research, fueled by advancements in technology allowing for more precise quantification of bacterial species. A person's age, diet, and living environment each play a critical role in shaping their gut microbiota. Dysbiosis, arising from modifications in these contributing elements, might result in adjustments to bacterial metabolites, which control the balance of pro- and anti-inflammatory processes, subsequently impacting bone well-being. The restoration of a healthy microbiome could have a role in reducing inflammation and potentially decreasing bone loss, a concern for those with osteoporosis or during space missions. Current research is, however, hampered by conflicting conclusions, insufficient numbers of subjects, and a lack of consistency in experimental conditions and control parameters. Despite advancements in sequencing techniques, the elusive nature of a globally consistent definition of a healthy gut microbiome persists. Challenges persist in pinpointing precise gut bacterial metabolic functions, identifying specific bacterial taxa, and understanding their influence on host physiology. Given the escalating cost of treating osteoporosis in the United States, reaching billions of dollars annually, with predicted future increases, Western nations should intensify their focus on this issue.
The occurrence of senescence-associated pulmonary diseases (SAPD) is linked to the physiological aging of lungs. The objective of this study was to identify the mechanism and subtype of aging T cells that influence alveolar type II epithelial cells (AT2), a factor implicated in the pathogenesis of senescence-associated pulmonary fibrosis (SAPF). To assess the cell proportions, the relationship between SAPD and T cells, and the aging- and senescence-associated secretory phenotype (SASP) of T cells between young and aged mice, lung single-cell transcriptomics was employed. T cells' induction of SAPD was detected through the monitoring of AT2 cell markers. Furthermore, the activation of IFN signaling pathways was observed, along with evidence of cellular senescence, the senescence-associated secretory phenotype (SASP), and T-cell activation in aged lungs. Aged T cells, experiencing senescence and the senescence-associated secretory phenotype (SASP) and stimulated by physiological aging, contributed to pulmonary dysfunction and senescence-associated pulmonary fibrosis (SAPF), driven by TGF-1/IL-11/MEK/ERK (TIME) signaling.