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aging hallmark

Claire E J Waterborg, Marije I Koenders, Peter L E M van Lent, Peter M van der Kraan, Fons A J van de Loo
Rheumatoid arthritis is an auto-immune disease of the synovial joints, hallmarked by chronic inflammation and subsequent progressive tissue destruction. TYRO3, AXL and MER (gene name Mertk) (TAM) receptors are part of a negative feedback signaling system in the immune reaction and mediate efferocytosis thereby tempering the inflammatory process. We have shown that Axl-/- and Mertk-/- mice develop more severe arthritis whereas activating these receptors by overexpressing their ligands Pros1 and Gas6 ameliorates arthritis...
2018: PloS One
Francesca Riuzzi, Guglielmo Sorci, Roberta Sagheddu, Sara Chiappalupi, Laura Salvadori, Rosario Donato
Emerging evidence suggests that the signalling of the Receptor for Advanced Glycation End products (RAGE) is critical for skeletal muscle physiology controlling both the activity of muscle precursors during skeletal muscle development and the correct time of muscle regeneration after acute injury. On the other hand, the aberrant re-expression/activity of RAGE in adult skeletal muscle is a hallmark of muscle wasting that occurs in response to ageing, genetic disorders, inflammatory conditions, cancer, and metabolic alterations...
October 18, 2018: Journal of Cachexia, Sarcopenia and Muscle
Yoshinaga Okugawa, Yuji Toiyama, Akira Yamamoto, Tsunehiko Shigemori, Ayame Kitamura, Takashi Ichikawa, Shozo Ide, Takahito Kitajima, Hiroyuki Fujikawa, Hiromi Yasuda, Yoshiki Okita, Junichiro Hiro, Toshimitsu Araki, Donald C McMillan, Chikao Miki, Masato Kusunoki
BACKGROUND: The systemic inflammatory response (SIR) via host-tumor interactions has been termed the seventh hallmark of cancer, and several studies demonstrated that SIR might be a pivotal mediator for progression of cancer cachexia. The objective of this study was to clarify the correlation between sarcopenia and SIR in patients with colorectal cancer (CRC). METHODS: A total of 308 patients with CRC were enrolled in this study. Preoperative psoas muscle mass index and intramuscular adipose tissue content were evaluated using preoperative computed tomographic images, and the correlation between body composition status and several SIR markers, including C-reactive protein (CRP), serum albumin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammation index (SII) was assessed using statistical methods...
October 18, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
Josephine Nehring, Lucia A Schirmbeck, Justa Friebus-Kardash, Denise Dubler, Uyen Huynh-Do, Carlo Chizzolini, Camillo Ribi, Marten Trendelenburg
Objectives: Autoantibodies and aberrant immune complexes are pathological hallmarks of systemic lupus erythematosus (SLE). This study aimed to determine the occurrence of IgG autoantibodies against human serum albumin (anti-HSA IgG) and their potential association with antibodies against bovine serum albumin (anti-BSA IgG) in patients with SLE. Methods: Sera of 180 SLE patients included to the Swiss SLE Cohort Study and 188 age- and sex-matched healthy controls were evaluated. Levels of anti-HSA IgG and anti-BSA IgG were quantified by ELISA...
2018: Frontiers in Immunology
Olga Simo-Servat, Cristina Hernández, Rafael Simó
BACKGROUND: Microvascular complications remain an important cause of morbidity in diabetic patients, and they are associated with a significant economic burden for healthcare systems. Vascular leakage is one of the earlier hallmarks in diabetic microvascular complications. Ezrin, radixin and moesin (ERM) proteins have recently been involved in vascular dysfunction under the effect of molecular mediators of diabetes complications. In this review we will present the available evidence regarding the role of these proteins in vascular leakage and their putative implication in diabetic microvascular complications...
October 16, 2018: Current Medicinal Chemistry
Ryan O Walters, Esperanza Arias, Antonio Diaz, Emmanuel S Burgos, Fangxia Guan, Simoni Tiano, Kai Mao, Cara L Green, Yungping Qiu, Hardik Shah, Donghai Wang, Adam D Hudgins, Tahmineh Tabrizian, Valeria Tosti, David Shechter, Luigi Fontana, Irwin J Kurland, Nir Barzilai, Ana Maria Cuervo, Daniel E L Promislow, Derek M Huffman
A hallmark of aging is a decline in metabolic homeostasis, which is attenuated by dietary restriction (DR). However, the interaction of aging and DR with the metabolome is not well understood. We report that DR is a stronger modulator of the rat metabolome than age in plasma and tissues. A comparative metabolomic screen in rodents and humans identified circulating sarcosine as being similarly reduced with aging and increased by DR, while sarcosine is also elevated in long-lived Ames dwarf mice. Pathway analysis in aged sarcosine-replete rats identify this biogenic amine as an integral node in the metabolome network...
October 16, 2018: Cell Reports
Courtney Nguyen, Shirley Leanos, Misaki N Natsuaki, George W Rebok, Rachel Wu
Maintenance of functional independence, or the ability to perform daily tasks independently, is a hallmark of successful aging. Healthy older adults are considered functionally independent if they pass a short survey consisting of relatively simple daily activities, including grocery shopping and managing finances. We argue that aging research often has overlooked an important factor for long-term functional independence in a dynamic environment: adaptation for growth via learning new skills. Previous research has focused primarily on compensation and mitigating decline rather than growth...
October 12, 2018: Gerontologist
Jessica E Manousakis, Anna J Scovelle, Shantha M W Rajaratnam, Sharon L Naismith, Clare Anderson
BACKGROUND: Increased sleep fragmentation and advanced circadian timing are hallmark phenotypes associated with increased age-related cognitive decline. Subjective cognitive decline (SCD) is considered a prodromal stage of neurodegeneration and dementia; however, little is known about how sleep and circadian timing impact on memory complaints in SCD. OBJECTIVE: To determine how sleep and circadian timing impact on memory complaint subtypes in older adults with SCD...
October 6, 2018: Journal of Alzheimer's Disease: JAD
Janaina Balthazar, Natalia Mendes Schöwe, Gabriela Cabett Cipolli, Hudson Sousa Buck, Tania Araujo Viel
Alzheimer's disease (AD) is associated with a progressive dementia, and there is good evidence that it is more pronounced in individuals that have fewer stimuli during their lives. Environmental stimulation promotes morphological and functional changes in the brain, leading to amplification of cognitive functions, and has been described in humans and animals. In this study, we evaluated the effects of enriched environment (EE) stimulation on spatial memory and senile plaque formation in transgenic mice PDGFB-APPSwInd (TG) that overexpress the human amyloid precursor protein, normally resulting in an increased density of senile plaques...
2018: Frontiers in Aging Neuroscience
Shenandoah Robinson, Fatu S Conteh, Akosua Y Oppong, Tracylyn R Yellowhair, Jessie C Newville, Nagat El Demerdash, Christine L Shrock, Jessie R Maxwell, Stephen Jett, Frances J Northington, Lauren L Jantzie
Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a global challenge. Early preterm infants (<32 weeks gestation), particularly those exposed to chorioamnionitis (CAM), are prone to intraventricular hemorrhage (IVH) and PHHP. We established an age-appropriate, preclinical model of PHHP with progressive macrocephaly and ventriculomegaly to test whether non-surgical neonatal treatment could modulate PHHP. We combined prenatal CAM and postnatal day 1 (P1, equivalent to 30 weeks human gestation) IVH in rats, and administered systemic erythropoietin (EPO) plus melatonin (MLT), or vehicle, from P2 to P10...
2018: Frontiers in Cellular Neuroscience
Martin Berger, Ferda Kaleagasıoglu, Maya Margaritova Zaharieva, Spiro M Konstantinov
Alkylphospholipids (APLs) are synthetically derived from cell membrane components. They target cell membranes and modify cellular signalling, thus originating diverse effects, including anti¬cancer, antiprotozoal, antibacterial and antiviral activities. Their actions probably initiate from targeting lipid rafts and altering phospholipase D and C signalling cascades, which in turn will modulate the PI3K/Akt/mTOR and RAS/RAF/MEK/ERK pathways. By feedback coupling, the SAPK/JNK signalling chain will also be affected...
October 11, 2018: Anti-cancer Agents in Medicinal Chemistry
Katherine R Sadleir, Jelena Popovic, Robert Vassar
Alzheimer's disease (AD) mouse models that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1) form β-amyloid (Aβ) plaques, a hallmark AD lesion. It has been assumed that the neuroinflammation, synaptic dysfunction, neurodegeneration, and cognitive impairment observed in these mice are caused by cerebral Aβ accumulation. However, it is also possible that accumulation of overexpressed transmembrane proteins APP and PS1 in the endoplasmic reticulum (ER) triggers chronic ER stress and activation of the unfolded protein response (UPR)...
October 12, 2018: Journal of Biological Chemistry
Sang Pil Yoon, Jinu Kim
The hallmark of cisplatin-induced acute kidney injury is the necrotic cell death in the kidney proximal tubules. However, an effective approach to limit cisplatin nephrotoxicity remains unknown. Spermidine is a polyamine that protects against oxidative stress and necrosis in aged yeasts, and the present study found that exogenous spermidine markedly attenuated tubular necrosis and kidney dysfunction, but not apoptosis, during cisplatin nephrotoxicity. In addition, exogenous spermidine potently inhibited oxidative/nitrative DNA damage, poly(ADP-ribose) polymerase 1 (PARP1) activation and ATP depletion after cisplatin injection...
September 2018: Anatomy & Cell Biology
Alyaa Al-Ibraheemi, Andrew L Folpe, Antonio R Perez-Atayde, Kyle Perry, Jakob Hofvander, Elsa Arbajian, Linda Magnusson, Jenny Nilsson, Fredrik Mertens
Lipofibromatosis is a rare pediatric soft tissue tumor with predilection for the hands and feet. Previously considered to represent "infantile fibromatosis", lipofibromatosis has distinctive morphological features, with mature adipose tissue, short fascicles of bland fibroblastic cells, and lipoblast-like cells. Very little is known about the genetic underpinnings of lipofibromatosis. Prompted by our finding of the FN1-EGF gene fusion, previously shown to be a characteristic feature of calcifying aponeurotic fibroma (CAF), in a morphologically typical case of lipofibromatosis that recurred showing features of CAF, we studied a cohort of 20 cases of lipofibromatosis for this and other genetic events...
October 11, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Shanat Baig, Richard Paisey, Charlotte Dawson, Timothy Barrett, Pietro Maffei, James Hodson, Srinivasa Bhargav Rambhatla, Priyesh Chauhan, Shaun Bolton, Francesca Dassie, Clair Francomano, Robert P Marshall, Mohammed Belal, Kassiani Skordilis, Manvir Hayer, Anna M Price, Robert Cramb, Nicola Edwards, Richard P Steeds, Tarekegn Geberhiwot
Background: Alström syndrome (AS) is a rare autosomal recessive ciliopathy with a wide spectrum of clinical features, including cone-rod retinal dystrophy, neuronal deafness, severe insulin resistance and major organ failure. The characteristics of renal disease in the syndrome have not been systematically described. The aim of this study is to define the onset and progression of renal disease in AS. Method: Prospective observational cohort study. Setting and Participants: Thirty-two adult subjects from a national specialist clinic in UK and 86 subjects from an international AS registry were studied...
October 10, 2018: Nephrology, Dialysis, Transplantation
Milan Stoiljkovic, Craig Kelley, Tamas L Horvath, Mihály Hajós
BACKGROUND: Translational research in Alzheimer's disease (AD) pathology provides evidence that accumulation of amyloid-β and hyperphosphorylated tau, neuropathological hallmarks of AD, is associated with complex disturbances in synaptic and neuronal function leading to oscillatory abnormalities in the neuronal networks that support memory and cognition. Accordingly, our recent study on transgenic TgF344-AD rats modeling AD showed an age-dependent reduction of stimulation-induced oscillations in the hippocampus, and disrupted long-range connectivity together with enhanced neuronal excitability in the cortex, reflected in greatly increased expression of high-voltage spindles, an epileptic absence seizure-like activity...
October 10, 2018: Alzheimer's Research & Therapy
Marianna Alperin, Lindsey Burnett, Emily Lukacz, Linda Brubaker
OBJECTIVES: A significant body of knowledge implicates menopausal estrogen levels in the pathogenesis of the common pelvic floor disorders (PFDs). These health conditions substantially decrease quality of life, increase depression, social isolation, caregiver burden, and economic costs to the individuals and society. METHODS: This review summarizes the epidemiology of the individual PFDs with particular attention to the understanding of the relationship between each PFD and menopausal estrogen levels, and the gaps in science and clinical care that affect menopausal women...
October 8, 2018: Menopause: the Journal of the North American Menopause Society
Martin Fruth, Bjoern Buehring, Xenofon Baraliakos, Juergen Braun
OBJECTIVES: To identify inflammatory pelvic structures of patients with polymyalgia rheumatica (PMR) by magnetic resonance imaging (MRI) in detail, searching for a disease-specific pattern. METHODS: A total of 40 contrast-enhanced pelvic MRIs of patients with a clinical diagnosis of PMR was reviewed by an experienced musculoskeletal radiologist who assessed all abnormalities semi-quantitatively, based on a predefined scoring system. RESULTS: The median (25th/75th percentiles) age of patients was 67 (55/73) years, median symptom duration 13 (6/22) weeks, 55% female, median CRP 1...
September 2018: Clinical and Experimental Rheumatology
Jennifer A Honeycutt, James J Chrobak
A marked decrease in parvalbumin (PV), a calcium-binding protein specific to a subset of GABAergic neurons, is a consistent finding in postmortem schizophrenic brain tissue. This reduction is selective to PV and is regionally specific, occurring primarily in the prefrontal cortex and hippocampus (HPC) of patients. Rodent models of NMDA receptor hypofunction utilizing NMDA antagonist treatments - e.g. ketamine (KET) - show schizophrenia-like cognitive and behavioral impairments with parallel changes in PV. While decreased PV is considered a hallmark of neuropathology in schizophrenia, previous work elucidating the effects of KET administration on PV are contradictory, with findings suggesting decreased, increased, or no change in PV expression...
October 6, 2018: Neuroscience
Jose Cordoba-Chacon, Andre Sarmento-Cabral, Mercedes Del Rio-Moreno, Alberto Diaz-Ruiz, Papasani V Subbaiah, Rhonda D Kineman
Nonalcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is associated with reduced growth hormone (GH) input/signaling and GH therapy is effective in the reduction/resolution of NAFLD/NASH in select patient populations. Our laboratory has focused on isolating the direct vs. indirect effects of GH in preventing NAFLD/NASH. We reported that chow-fed, adult-onset hepatocyte-specific GH receptor knockdown (aHepGHRkd) mice rapidly (within 7d) develop steatosis associated with increased hepatic de novo lipogenesis (DNL), independent of changes in systemic metabolic function...
October 5, 2018: Endocrinology
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