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aging hallmark

Kelsey J Moody, Jay Tinklepaugh, Elizabeth Obert, Kris Grohn, Jennifer R DeRosa, Ellie Lumen, Brandon Scott Moyer, Scott Campbell, Aaron J Wolfe, Meegan B Sleeper, Anthony H Bianchi, Cheyanne Fisher, Justin Applegate, Emily Leary, Nick LeClair, Danique Wortel, Robert Patrick Doyle, Baerbel Rohrer, Adam R Blanden
Macular degeneration is hallmarked by retinal accumulation of toxic retinoid species (e.g. A2E) for which there is no endogenous mechanism to eliminate. This ultimately results in progressive dysfunction and loss of vision either in advanced age for genetically normal patients (age-related macular degeneration), or in adolescence for those with inherited genetic mutations (Stargardt's disease). Here, we present a proof-of-concept study for an enzyme-based therapy to remove these retinoids, modeled on traditional enzyme replacement therapy...
December 5, 2018: Rejuvenation Research
Bob Olsson, Erik Portelius, Nicholas C Cullen, Åsa Sandelius, Henrik Zetterberg, Ulf Andreasson, Kina Höglund, David J Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David Wolk, Leo McCluskey, Lauren Elman, Leslie M Shaw, Jon B Toledo, Jennifer McBride, Pilar Hernandez-Con, Virginia M-Y Lee, John Q Trojanowski, Kaj Blennow
Importance: Neuronal and axonal destruction are hallmarks of neurodegenerative diseases, but it is difficult to estimate the extent and progress of the damage in the disease process. Objective: To investigate cerebrospinal fluid (CSF) levels of neurofilament light (NFL) protein, a marker of neuroaxonal degeneration, in control participants and patients with dementia, motor neuron disease, and parkinsonian disorders (determined by clinical criteria and autopsy), and determine its association with longitudinal cognitive decline...
December 3, 2018: JAMA Neurology
Maliha Khan, Rabbia Siddiqi, Thai Hoa Tran
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high-risk subtype of B-lineage ALL (B-ALL), characterized by a gene expression profile similar to that of Philadelphia-positive (Ph+) ALL, but without the hallmark BCR-ABL1 oncoprotein. Ph-like ALL represents approximately 15% of childhood ALL and its frequency rises with age, peaking among adolescents, and young adults with B-ALL. This subtype is associated with adverse clinical features, persistence of minimal residual disease, and a poor prognosis despite modern chemotherapy regimens...
October 2018: Seminars in Hematology
Hernán H Dieguez, Horacio E Romeo, Agustina Alaimo, María F González Fleitas, Marcos L Aranda, Ruth E Rosenstein, Damián Dorfman
Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its high metabolic demand, mitochondria concentration, reactive oxygen species levels, and macular blood flow. It has been suggested that oxidative stress-induced damage to the RPE plays a key role in NE-AMD pathogenesis. The fact that the disease limits to the macular region raises the question as to why this area is particularly susceptible...
November 28, 2018: Free Radical Biology & Medicine
Vahid Nejati, Elham Fathi, Shahriar Shahidi, Mohammad Ali Salehinejad
Depressed individuals interpret ambiguous information more negatively and this has been suggested a central component in cognitive models of depression. In this study we investigated the effectiveness of the interpretation modification training on modifying interpretation bias in depression and its association with symptoms reduction. In a double-blind, randomized controlled design, twenty-two depressed individuals (mean age = 19.86, SD = 1.16) were randomly assigned to the experimental and control groups...
November 17, 2018: Asian Journal of Psychiatry
Ramona Belfiore, Alexis Rodin, Eric Ferreira, Ramon Velazquez, Caterina Branca, Antonella Caccamo, Salvatore Oddo
Accumulation of amyloid-β (Aβ) and fibrillary tangles, as well as neuroinflammation and memory loss, are hallmarks of Alzheimer's disease (AD). After almost 15 years from their generation, 3xTg-AD mice are still one of the most used transgenic models of AD. Converging evidence indicates that the phenotype of 3xTg-AD mice has shifted over the years and contradicting reports about onset of pathology or cognitive deficits are apparent in the literature. Here, we assessed Aβ and tau load, neuroinflammation, and cognitive changes in 2-, 6-, 12-, and 20-month-old female 3xTg-AD and nontransgenic (NonTg) mice...
November 28, 2018: Aging Cell
Hui Yan, Wangbao Yang, Fenghua Zhou, Xiaopeng Li, Quan Pan, Zheng Shen, Guichun Han, Annie Newell-Fugate, Yanan Tian, Ravikumar Majeti, Wenshe Liu, Yong Xu, Chaodong Wu, Kimberly Allred, Clinton Allred, Yuxiang Sun, Shaodong Guo
Premenopausal women exhibit enhanced insulin sensitivity and reduced incidence of type 2 diabetes mellitus (T2D) compared with age-matched men, but this advantage disappears after menopause with disrupted glucose homeostasis, in part owing to a reduction in circulating 17β-estradiol (E2 ). Fasting hyperglycemia is a hallmark of T2D derived largely from dysregulation of hepatic glucose production (HGP), in which Foxo1 plays a central role in the regulation of gluconeogenesis. Here, we investigated the action of E2 on glucose homeostasis in male and ovariectomized (OVX) female control and liver-specific Foxo1 knockout (L-F1KO) mice, and sought to understand the mechanism by which E2 regulates gluconeogenesis via an interaction with hepatic Foxo1...
November 28, 2018: Diabetes
Peter H Sudmant, Hyeseung Lee, Daniel Dominguez, Myriam Heiman, Christopher B Burge
Particular brain regions and cell populations exhibit increased susceptibility to aging-related stresses. Here, we describe the age-specific and brain-region-specific accumulation of ribosome-associated 3' UTR RNAs that lack the 5' UTR and open reading frame. Our study reveals that this phenomenon impacts hundreds of genes in aged D1 spiny projection neurons of the mouse striatum and also occurs in the aging human brain. Isolated 3' UTR accumulation is tightly correlated with mitochondrial gene expression and oxidative stress, with full-length mRNA expression that is reduced but not eliminated, and with production of short 3' UTR-encoded peptides...
November 27, 2018: Cell Reports
Kirsty E McAleese, Sophie Graham, Madhurima Dey, Lauren Walker, Daniel Erskine, Mary Johnson, Eleanor Johnston, Alan J Thomas, Ian G McKeith, Charles DeCarli, Johannes Attems
The blood-brain barrier (BBB) regulates cerebrovascular permeability and leakage of blood-derived fibrinogen has been associated with cerebral arteriolosclerosis small vessel disease (SVD) and subsequent white matter lesions (WML). Furthermore, BBB-dysfunction is associated with the pathogenesis of Alzheimer's disease (AD) with the presence of CSF plasma proteins suggested to be a potential biomarker of AD. We aimed to determine if extravascular fibrinogen in the white matter was associated with the development of AD hallmark pathologies, i...
November 28, 2018: Brain Pathology
Alice Brambilla, Silvia Favilli, Iacopo Olivotto, Giovanni Battista Calabri, Giulio Porcedda, Luciano De Simone, Elena Procopio, Elisabetta Pasquini, Maria Alice Donati
BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like (MELAS) syndrome is a rare condition with heterogeneous clinical presentation. Cardiac involvement commonly develops during adulthood, comprising both structural and conduction/arrhythmic abnormalities; early paediatric onset has rarely been reported. We describe the clinical profile, outcome and clinical implication of MELAS-associated cardiomyopathy at a tertiary referral centre. METHODS: From 2000 to 2016 we enrolled 21 patients affected by genetically-proven MELAS...
October 23, 2018: International Journal of Cardiology
Francesca Lovat, Matteo Fassan, Diana Sacchi, Parvathi Ranganathan, Alexey Palamarchuk, Marius Bill, Malith Karunasiri, Pierluigi Gasparini, Giovanni Nigita, Rosario Distefano, Dario Veneziano, Adrienne M Dorrance, Ramiro Garzon, Carlo M Croce
MicroRNAs (miRNAs) have been extensively reported to be associated with hematological malignancies. The loss of miR-15a/16-1 at chromosome 13q14 is a hallmark of most of human chronic lymphocytic leukemia (CLL). Deletion of murine miR-15a/16-1 and miR-15b/16-2 has been demonstrated to promote B cell malignancies. Here, we evaluate the biological role of miR-15/16 clusters, crossbreeding miR-15a/16-1 and miR-15b/16-2 knockout mice. Unexpectedly, the complete deletion of both clusters promoted myeloproliferative disorders in the majority of the mice by the age of 5 months with a penetrance of 70%...
November 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Nienke Legdeur, Maryam Badissi, Stephen F Carter, Sophie de Crom, Aleid van de Kreeke, Ralph Vreeswijk, Marijke C Trappenburg, Mardien L Oudega, Huiberdina L Koek, Jos P van Campen, Carolina J P W Keijsers, Chinenye Amadi, Rainer Hinz, Mark F Gordon, Gerald Novak, Jana Podhorna, Erik Serné, Frank Verbraak, Maqsood Yaqub, Arjan Hillebrand, Alessandra Griffa, Neil Pendleton, Sophia E Kramer, Charlotte E Teunissen, Adriaan Lammertsma, Frederik Barkhof, Bart N M van Berckel, Philip Scheltens, Majon Muller, Andrea B Maier, Karl Herholz, Pieter Jelle Visser
BACKGROUND: The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old. In this paper we reviewed previous studies on cognitive resilience in the oldest-old and described the design of the EMIF-AD 90+ Study...
November 26, 2018: BMC Geriatrics
Saeideh Momtaz, Maryam Baeeri, Mahban Rahimifard, Hamed Haghi-Aminjan, Shokoufeh Hassani, Mohammad Abdollahi
Aging contributes to an increased risk of developing a number of neurodegenerative and chronic disorders, predominantly related to oxidative stress (OS) and defects in the antioxidant balance. This study focused on the antisenescence effect of four plant species (Falcaria vulgaris, Ixiolirion tataricum, Ajuga chamaecistus, and Scabiosa flavida) on H2 O2 -induced premature senescence in rat NIH3T3 fibroblasts, which were found to be rich in effective phytochemicals with traditional ethnobotanical backgrounds...
November 26, 2018: Journal of Cellular Biochemistry
Sophia V Rizou, Konstantinos Evangelou, Vassilios Myrianthopoulos, Iordanis Mourouzis, Sophia Havaki, Aikaterini Athanasiou, Panagiotis V S Vasileiou, Aggelos Margetis, Athanassios Kotsinas, Nikolaos G Kastrinakis, Petros Sfikakis, Paul Townsend, Emmanuel Mikros, Constantinos Pantos, Vassilis G Gorgoulis
Lipofuscin accumulation is a hallmark of senescence. This nondegradable material aggregates in the cytoplasm of stressed or damaged cells due to metabolic imbalance associated with aging and age-related diseases. Indications of a soluble state of lipofuscin have also been provided, rendering the perspective of monitoring such processes via lipofuscin quantification in liquids intriguing. Therefore, the development of an accurate and reliable method is of paramount importance. Currently available assays are characterized by inherent pitfalls which demote their credibility...
2019: Methods in Molecular Biology
Tjing-Tjing Hu, Marc Vanhove, Michaël Porcu, Inge Van Hove, Tine Van Bergen, Bart Jonckx Bart, Philippe Barbeaux, Elke Vermassen, Jean H M Feyen
Integrins are associated with various eye diseases such as diabetic retinopathy (DR) and wet age-related macular degeneration (AMD) and implicated in main pathologic disease hallmarks like neovascularization, inflammation, fibrosis and vascular leakage. Targeting integrins has the potential to attenuate these vision-threatening processes, independent of anti-vascular endothelial growth factor (VEGF) responsiveness. The current investigation characterized THR-687 as a novel pan RGD (arginylglycylaspartic acid) integrin receptor antagonist able to compete for binding with the natural ligand with nanomolar potency (e...
November 22, 2018: Experimental Eye Research
Sarah Louise Fishman, Halis Sonmez, Craig Basman, Varinder Singh, Leonid Poretsky
BACKGROUND: Traditional risk factors are insufficient to explain all cases of coronary artery disease (CAD) in patients with diabetes mellitus (DM). Advanced glycation end-products (AGEs) and their receptors may play important roles in the development and progression of CAD. BODY: Hyperglycemia is the hallmark feature of DM. An increase in the incidence of both micro-and macrovascular complications of diabetes has been observed with increased duration of hyperglycemia. This association persists even after glycemic control has been achieved, suggesting an innate mechanism of "metabolic memory...
November 23, 2018: Molecular Medicine
Camilla Thygesen, Laura Ilkjær, Stefan J Kempf, Anne Louise Hemdrup, Christian Ulrich von Linstow, Alicia A Babcock, Sultan Darvesh, Martin R Larsen, Bente Finsen
Neuroinflammation, characterized by chronic activation of the myeloid-derived microglia, is a hallmark of Alzheimer's disease (AD). Systemic inflammation, typically resulting from infection, has been linked to the progression of AD due to exacerbation of the chronic microglial reaction. However, the mechanism and the consequences of this exacerbation are largely unknown. Here, we mimicked systemic inflammation in AD with weekly intraperitoneal (i.p.) injections of APPSWE /PS1ΔE9 transgenic mice with E. coli lipopolysaccharide (LPS) from 9 to 12 months of age, corresponding to the period with the steepest increase in amyloid pathology...
2018: Frontiers in Cellular Neuroscience
Maria Camila Almeida, Daniel Carneiro Carrettiero
Alzheimer disease (AD), which is associated with chronic and progressive neurodegeneration, is the most prevalent cause of dementia linked to aging. Among the risk factors for AD, age stands as the greatest one, with the vast majority of people with AD being 65 years of age or older. Nevertheless, the pathophysiologic mechanisms underlying the link between aging and the development of AD, although not completely understood, might reveal important aspects for the understanding of this pathology. Thus, there is significant evidence that the impaired thermal homeostasis associated with normal aging leads to a variety of metabolic changes that could be associated with AD development...
2018: Handbook of Clinical Neurology
Eleni A Greenwood, Lauri A Pasch, Kanade Shinkai, Marcelle I Cedars, Heather G Huddleston
OBJECTIVE: To [1] characterize depression symptoms over time and [2] test the hypothesis that adverse metabolic parameters would associate with risk of enduring depression risk in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective cohort study. SETTING: University center. PATIENT(S): One hundred sixty-three women with PCOS. INTERVENTION(S): The Beck Depression Inventory Fast Screen (BDI-FS) was self-administered at baseline and follow-up to identify depression risk, using a cutoff score >4...
November 17, 2018: Fertility and Sterility
Mari Yamagami, Motoyuki Otsuka, Takahiro Kishikawa, Kazuma Sekiba, Takahiro Seimiya, Eri Tanaka, Tatsunori Suzuki, Rei Ishibashi, Motoko Ohno, Kazuhiko Koike
During cellular aging, many changes in cellular functions occur. A hallmark of aged cells is secretion of inflammatory mediators, which collectively is referred to as the senescence-associated secretory phenotype (SASP). However, the mechanisms underlying such changes are unclear. Canonically, the expression of interferon (IFN)-stimulated genes (ISGs) is induced by IFNs through the formation of the tripartite transcriptional factor ISGF3, which is composed of IRF9 and the phosphorylated forms of STAT1 and STAT2...
2018: NPJ Aging and Mechanisms of Disease
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