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aging hallmark

Jacqueline Chua, Calvin Woon Loong Chin, Jimmy Hong, Miao Li Chee, Thu-Thao Le, Daniel Shu Wei Ting, Tien Yin Wong, Leopold Schmetterer
OBJECTIVE: Reduction in capillary density or rarefaction is a hallmark of essential hypertension. We measured the retinal capillary density using noninvasive optical coherence tomographic angiography (OCT-A) in adults with treated systemic hypertension and determined possible correlations with ambulatory blood pressure (BP) and renal parameters. METHODS: This observational cross-sectional study consisted of 153 normal eyes from 77 nondiabetic hypertensive adults [mean (SD) age, 58 (9) years; 49% women; 23% poorly controlled BP]...
August 14, 2018: Journal of Hypertension
Masahir Okamoto, Jason D Gray, Chloe S Larson, Syed Faraz Kazim, Hideaki Soya, Bruce S McEwen, Ana C Pereira
Alzheimer's disease (AD) represents a major healthcare burden with no effective treatment. The glutamate modulator, riluzole, was shown to reverse many AD-related gene expression changes and improve cognition in aged rats. However, riluzole's effect on amyloid beta (Aβ) pathology, a major histopathological hallmark of AD, remains unclear. 5XFAD transgenic mice, which harbor amyloid β precursor protein (APP) and presenilin mutations and exhibit early Aβ accumulation, were treated with riluzole from 1 to 6 months of age...
August 14, 2018: Translational Psychiatry
Yuta Takaichi, Yasuhisa Ano, James K Chambers, Kazuyuki Uchida, Akihiko Takashima, Hiroyuki Nakayama
The accumulation of specific phosphorylated protein aggregates in the brain is a hallmark of severe neurodegenerative disorders. Specifically, hyperphosphorylated tau (hp-tau) accumulates in Alzheimer disease, frontotemporal dementia with Parkinsonism linked to chromosome 17, and progressive supranuclear palsy; furthermore, phosphorylated α-synuclein (p-αSyn) accumulates in Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. Moreover, codeposition of different pathological protein aggregates is common in the brains of individuals with neurodegenerative diseases...
July 18, 2018: Journal of Neuropathology and Experimental Neurology
Jiaqing Cao, Xinyou Han, Xin Qi, Xiangyun Jin, Xiaolin Li
One of the hallmarks of osteoarthritis (OA) development is endochondral ossification, in which Runt‑related transcription factor‑2 (Runx2) is aberrantly expressed. Runx2 was previously identified to be regulated by microRNA‑204‑5p (miR‑204‑5p). The aim of the present study was to investigate the potential function of miR‑204‑5p regulating Runx2 during the development of OA and the underlying molecular mechanism. The expression levels of miR‑204‑5p and Runx2 were determined in tissue specimens...
August 7, 2018: International Journal of Molecular Medicine
Manas R Biswal, Howard M Prentice, George W Smith, Ping Zhu, Yao Tong, C Kathleen Dorey, Alfred S Lewin, Janet C Blanks
Aberrant growth of blood vessels in the choroid layer of the eye, termed choroidal neovascularization (CNV), is the pathological hallmark of exudative age-related macular degeneration (AMD), causing irreversible blindness among the elderly. Co-localization of proangiogenic factors and hypoxia inducible factors (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell-specific gene therapy to inhibit choroidal neovascularization...
August 13, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Lingxuan Chen, Takashi Saito, Takaomi C Saido, Istvan Mody
Alzheimer's disease (AD) is a neurodegenerative disorder that has become a compelling global public health concern. Besides pathological hallmarks such as extracellular amyloid plaques, intracellular neurofibrillary tangles (NFTs), and loss of neurons and synapses, clinical reports have shown that epileptiform activity, even seizures, can occur early in the disease. Aberrant synaptic and network activities as well as epileptiform discharges have also been observed in various mouse models of AD. The new AppNL-F mouse model is generated by a gene knock-in approach and there are limited studies on basic synaptic properties in AppNL-F mice...
July 2018: ENeuro
Yi-Tsung Yang, Yu-Chiao Chiu, Chein-Jun Kao, Hsin-An Hou, Chien-Chin Lin, Cheng-Hong Tsai, Mei-Hsuan Tseng, Wen-Chien Chou, Hwei-Fang Tien
Aberrant alternative splicing (AS) is a hallmark of cancer development. However, there are limited data regarding its clinical implications in myelodysplastic syndrome (MDS). In this study, we performed an in-depth analysis of global AS in 176 primary MDS patients with 20 normal marrow transplant donors as reference. We found that 26.9% of the expressed genes genome-wide were aberrantly spliced in MDS patients compared with normal donors. These aberrant AS genes were related to pathways involved in cell proliferation, cell adhesion and protein degradation...
August 13, 2018: Blood Cancer Journal
Irving E Vega, Andrew Umstead, Cassandra M Wygant, John S Beck, Scott E Counts
BACKGROUND: The lack of diagnostic tools and disease-modifying treatments against Alzheimer's disease (AD) and related disorders, collectively known as tauopathies, have led to a socioeconomic burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome changes that could help us understand the pathogenesis of tau-related pathological hallmarks and/or cellular stress responses associated with tauopathy. These studies, however, need to be conducted taking in consideration brain region specificity and stage of neurodegeneration in order to provide insights about the pathological role of the identified proteins...
August 13, 2018: Current Alzheimer Research
Giampiero Leanza, Rosario Gulino, Robert Zorec
In the past, manipulation of the cholinergic system was seen as the most likely therapeutic for neurodegeneration-based cognitive decline in Alzheimer's disease (AD) (Whitehouse et al., 1982). However, targeting the noradrenergic system also seems a promising strategy, since more recent studies revealed that in post-mortem tissue from patients with AD and other neurodegenerative disorders there is a robust correlation between cognitive decline and loss of neurons from the Locus coeruleus (LC), a system with diffuse noradrenaline (NA) innervation in the central nervous system (CNS)...
2018: Frontiers in Molecular Neuroscience
Barna Babik, Ferenc Peták, Szilvia Agócs, Ivett Blaskovics, Endre Alács, Kinga Bodó, Roberta Südy
Diabetes mellitus involves a group of chronic metabolic disorders with elevated blood glucose concentrations. Since this disease needs lifelong treatment and care, the medical and social aspects present major public health concerns and pose a global challenge for health care providers. The number of aged patients with degenerative diseases undergoing surgical procedures is continuously increasing, resulting in an overwhelming dominance of diabetes in the perioperative care. There is a particular need for an increased awareness of diabetic patients in cardiovascular units, where the incidence of this disease reaches as high as 30-40%...
August 2018: Orvosi Hetilap
Janice K Kiecolt-Glaser, Stephanie J Wilson, Michael L Bailey, Rebecca Andridge, Juan Peng, Lisa M Jaremka, Christopher P Fagundes, William B Malarkey, Bryon Laskowski, Martha A Belury
BACKGROUND: Marital distress and depression work in tandem to escalate risks for inflammation-related disorders. Translocation of bacterial endotoxin (lipopolysaccharide, LPS) from the gut microbiota to blood circulation stimulates systemic inflammatory responses. METHODS: To investigate increased gut permeability (a "leaky gut") as one potential mechanistic pathway from marital distress and depression to heightened inflammation, this secondary analysis of a double-blind, randomized crossover study examined serial assessments of two endotoxin biomarkers, LPS-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) during two separate 9...
August 4, 2018: Psychoneuroendocrinology
Maria Kondyli, Valérie Larouche, Christine Saint-Martin, Benjamin Ellezam, Lauranne Pouliot, Daniel Sinnett, Geneviève Legault, Louis Crevier, Alex Weil, Jean-Pierre Farmer, Nada Jabado, Sébastien Perreault
INTRODUCTION: Pediatric pilocytic astrocytomas (PAs) are low grade gliomas and the most common brain tumors in children. They often represent a therapeutic challenge when incompletely resected as they can recur and progress despite the use of several lines of chemotherapeutic agents or even radiation therapy. Genetic alterations leading to activation of the mitogen-activated-protein-kinase pathway are a hallmark of this disease and offer an interesting therapeutic alternative through the use of targeted inhibitors...
August 10, 2018: Journal of Neuro-oncology
Fadwa Cazala, Véronique Fonteille, Virginie Moulier, Mélanie Pélégrini-Issac, Christiane De Beaurepaire, Marlène Abondo, Magali Bodon-Bruzel, Jean Cano, Florent Cochez, Taoufik Fouli, Catherine Thevenon, Bernard Dauba, Michel Pugeat, Serge Stoléru
Structural and functional neuroimaging techniques have recently been used to investigate the mechanisms of sexual attraction to children, a hallmark of pedophilic disorder, and have reported many contradictory or non-replicated findings. Here, our purpose was to identify through functional magnetic resonance imaging the brain responses of 25 male outpatients with pedophilic disorder to visual stimuli depicting children (VSc) and to compare them with 24 male healthy controls matched on sexual orientation (to female or male adults), age, and handedness...
August 9, 2018: European Archives of Psychiatry and Clinical Neuroscience
Jurre den Haan, Tjado H J Morrema, Annemieke J Rozemuller, Femke H Bouwman, Jeroen J M Hoozemans
The combined fluorescent and Aβ-binding properties of the dietary spice curcumin could yield diagnostic purpose in the search for a non-invasive Aβ-biomarker for Alzheimer's disease (AD). However, evidence on the binding properties of curcumin, its conjugates and clinically used bio-available formulations to AD neuropathological hallmarks is scarce. We therefore assessed the binding properties of different curcumin forms to different neuropathological deposits in post-mortem brain tissue of cases with AD, other neurodegenerative diseases, and controls...
August 9, 2018: Acta Neuropathologica Communications
L Q Zhong, L Wang, H M Song, W Wang, M Wei, Y Y He
Objective: To analyze the clinical characteristics of spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Methods: The clinical manifestations, laboratory examinations, treatment and genetic analysis of a patient diagnosed with SPENCDI who was admitted to the Department of Pediatrics in Peking Union Medical College Hospital in October 2016 were analyzed. Then literature review was done after searching articles in PubMed and several Chinese databases with the key words "spondyloenchondrodysplasia with immune dysregulation" up to the date of November 2017...
August 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Carolin Göbel, Roman Goetzke, Thomas Eggermann, Wolfgang Wagner
Replicative senescence hampers application of mesenchymal stromal cells (MSCs) because it limits culture expansion, impairs differentiation potential, and hinders reliable standardization of cell products. MSCs can be rejuvenated by reprogramming into induced pluripotent stem cells (iPSCs), which is associated with complete erasure of age- and senescence-associated DNA methylation (DNAm) patterns. However, this process is also associated with erasure of cell-type and tissue-specific epigenetic characteristics that are not recapitulated upon re-differentiation towards MSCs...
August 3, 2018: Scientific Reports
Elles Konijnenberg, Stephen F Carter, Mara Ten Kate, Anouk den Braber, Jori Tomassen, Chinenye Amadi, Linda Wesselman, Hoang-Ton Nguyen, Jacoba A van de Kreeke, Maqsood Yaqub, Matteo Demuru, Sandra D Mulder, Arjan Hillebrand, Femke H Bouwman, Charlotte E Teunissen, Erik H Serné, Annette C Moll, Frank D Verbraak, Rainer Hinz, Neil Pendleton, Adriaan A Lammertsma, Bart N M van Berckel, Frederik Barkhof, Dorret I Boomsma, Philip Scheltens, Karl Herholz, Pieter Jelle Visser
BACKGROUND: Amyloid pathology is the pathological hallmark in Alzheimer's disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline...
August 4, 2018: Alzheimer's Research & Therapy
Joshua N Farr, Maria Almeida
Aging research has undergone unprecedented advances at an accelerating rate in recent years, leading to excitement in the field as well as opportunities for imagination and innovation. Novel insights indicate that, rather than resulting from a pre-programmed series of events, the aging process is predominantly driven by fundamental non-adaptive mechanisms that are interconnected, linked, and overlap. To varying degrees, these mechanisms also manifest with aging in bone where they cause skeletal fragility. Because these mechanisms of aging can be manipulated, it might be possible to slow, delay, or alleviate multiple age-related diseases and their complications by targeting conserved genetic signaling pathways, controlled functional networks, and basic biochemical processes...
August 3, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Ruy A Louzada, Denise P Carvalho
Thyroxine (T4) and 3,5,3'-triiodothyronine (T3) are secreted by the thyroid gland, while T3 is also generated from the peripheral metabolism of T4 by iodothyronine deiodinases types I and II. Several conditions like stress, diseases, and physical exercise can promote changes in local TH metabolism, leading to different target tissue effects that depend on the presence of tissue-specific enzymatic activities. The newly discovered physiological and pharmacological actions of T4 and T3 metabolites, such as 3,5-diiodothyronine (3,5-T2), and 3-iodothyronamine (T1AM) are of great interest...
2018: Frontiers in Endocrinology
Giacomo Baccolo, Giulia Stamerra, Coppola Damiano Pellegrino, Ivan Orlandi, Marina Vai
Mitochondrial functionality is one of the main factors involved in cell survival, and mitochondrial dysfunctions have been identified as an aging hallmark. In particular, the insurgence of mitochondrial dysfunctions is tightly connected to mitochondrial metabolism. During aging, both mitochondrial oxidative and biosynthetic metabolisms are progressively altered, with the development of malfunctions, in turn affecting mitochondrial functionality. In this context, the relation between mitochondrial pathways and aging is evolutionarily conserved from single-celled organisms, such as yeasts, to complex multicellular organisms, such as humans...
2018: International Review of Cell and Molecular Biology
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