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aging hallmark

Anna Picca, Flora Guerra, Riccardo Calvani, Cecilia Bucci, Maria Rita Lo Monaco, Anna Rita Bentivoglio, Hélio José Coelho-Júnior, Francesco Landi, Roberto Bernabei, Emanuele Marzetti
The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These "aging pillars" are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions...
February 13, 2019: International Journal of Molecular Sciences
Gabriela Corina Zaharie, Monica Hasmasanu, Ligia Blaga, Melinda Matyas, Daniel Muresan, Sorana Daniela Bolboaca
AIM: To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction (IUGR) pregnancies. MATERIAL AND METHOD: A cohort of IUGR infants were evaluated by serial echocardiographies at delivery and at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the control group according to gestational age (AGA). RESULTS: Left heart measurements were significantly lower in IUGR newborns compared to AGA babies...
February 17, 2019: Medical Ultrasonography
Veronika Städele, Eila R Roberts, Brendan J Barrett, Shirley C Strum, Linda Vigilant, Joan B Silk
Long-term male-female bonds and bi-parental investment in offspring are hallmarks of human society. A key question is how these traits evolved from the polygynandrously mating multimale multifemale society that likely characterized the Pan-Homo ancestor. In all three species of savanna baboons, lactating females form strong ties (sometimes called "friendships") with one or more adult males. For yellow baboons (Papio cynocephalus) and chacma baboons (Papio ursinus), several lines of evidence suggest that these relationships are a form of male parenting effort...
February 2019: Journal of Human Evolution
Alejandra Romero, Álvaro San Hipólito-Luengo, Laura A Villalobos, Susana Vallejo, Inés Valencia, Patrycja Michalska, Natalia Pajuelo-Lozano, Isabel Sánchez-Pérez, Rafael León, José Luis Bartha, María Jesús Sanz, Jorge D Erusalimsky, Carlos F Sánchez-Ferrer, Tania Romacho, Concepción Peiró
Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers...
February 17, 2019: Aging Cell
Orr Shauly, Daniel J Gould, Imran Siddiqi, Ketan M Patel, Joseph Carey
Anaplastic large-cell lymphoma (ALCL) is a very rare but life-threatening complication that has largely been demonstrated to be associated with breast implants (BIA-ALCL). Patients are at risk of BIA-ALCL with the placement of breast implants for either cosmetic or reconstructive purposes, with the highest risks associated with textured breast implants. In the past decade, there have been an increasing number of publications focused on BIA-ALCL, but there has yet to be a reported case outside of the breast...
February 15, 2019: Aesthetic Surgery Journal
Jeannie Chew, Casey Cook, Tania F Gendron, Karen Jansen-West, Giulia Del Rosso, Lillian M Daughrity, Monica Castanedes-Casey, Aishe Kurti, Jeannette N Stankowski, Matthew D Disney, Jeffrey D Rothstein, Dennis W Dickson, John D Fryer, Yong-Jie Zhang, Leonard Petrucelli
BACKGROUND: A G4 C2 hexanucleotide repeat expansion in the noncoding region of C9orf72 is the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). Putative disease mechanisms underlying c9FTD/ALS include toxicity from sense G4 C2 and antisense G2 C4 repeat-containing RNA, and from dipeptide repeat (DPR) proteins unconventionally translated from these RNA products. METHODS: Intracerebroventricular injections with adeno-associated virus (AAV) encoding 2 or 149 G4 C2 repeats were performed on postnatal day 0, followed by assessment of behavioral and neuropathological phenotypes...
February 15, 2019: Molecular Neurodegeneration
Youssef M Roman
Gout is the most common inflammatory arthritic condition affecting more men than women. Hyperuricemia and the deposition of urate crystals into the joints are the hallmarks of gout. The prevalence of gout and hyperuricemia is rising in the United States and world-wide possibly due to the aging population, comorbidities, and other lifestyle factors. Gout and serum uric acid (SUA) levels are highly heritable, underscoring the role of genetics on disease risk and possibly the racial disparities in gout prevalence...
February 2019: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
Jaikumar Ramamoorthy, Amita Trehan, Jasmina Ahluwalia, Paramjeet Singh, Rohit Manoj, Deepak Bansal
Independence from regular transfusions is the hallmark of nontransfusion-dependent thalassemia (NTDT). However, the associated complications need anticipation and screening. One such complication is a hypercoagulable state predisposing to development of thrombosis. We evaluated children with NTDT >10 years of age for prevalence of neuroimaging abnormalities (NIA) and identified associated risk factors. In total, 29 patients were evaluated. Blood counts, serum ferritin, protein C, protein S, antithrombin III, brain magnetic resonance imaging, and angiography was done in all patients...
February 12, 2019: Journal of Pediatric Hematology/oncology
Diogo R Feleciano, Katrin Juenemann, Manuel Iburg, Inês C Brás, Carina I Holmberg, Janine Kirstein
A functional protein quality control machinery is crucial to maintain cellular and organismal physiology. Perturbation in the protein homeostasis network can lead to the formation of misfolded and aggregated proteins that are a hallmark of protein conformational disorders and aging. Protein aggregation is counteracted by the action of chaperones that can resolubilize aggregated proteins. An alternative protein aggregation clearance strategy is the elimination by proteolysis employing the ubiquitin proteasome system (UPS) or autophagy...
2019: Frontiers in Aging Neuroscience
Rudy J Castellani, Germán Plascencia-Villa, George Perry
The identification of amyloid-β precursor protein (APP) pathogenic mutations in familial early onset Alzheimer's disease (AD), along with knowledge that amyloid-β (Aβ) was the principle protein component of senile plaques, led to the establishment of the amyloid cascade hypothesis. Down syndrome substantiated the hypothesis, given an extra copy of the APP gene and invariable AD pathology hallmarks that occur by middle age. An abundance of support for the amyloid cascade hypothesis followed. Prion-like protein misfolding and non-Mendelian transmission of neurotoxicity are among recent areas of investigation...
February 13, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
Nan He, Bradley H Rosen, Jaimie S Gray, Idil A Evans, Marina Zieger, Ziying Yan, Florie Borel, Bo Liang, Xingshen Sun, Shashanna R Moll, Michael H Brodsky, Christian Mueller, John F Engelhardt
RATIONALE: The most prevalent genetic cause of chronic obstructive pulmonary disease is alpha-1 antitrypsin (A1AT) deficiency, a disorder that has yet to be widely modeled in animals because of species-specific differences between rodents and humans. OBJECTIVES: To address these challenges, we engineered two A1AT ferret models using zygote gene editing to test the hypothesis that unopposed protease activity within the lung leads to emphysema and bronchitis. METHODS: Guide RNAs targeting exon 2 (for knockout) and exon 5 (for Z-allele mutation, Pi*Z) of the ferret A1AT gene were injected into ferret zygotes with Cas9 mRNA...
December 2018: Annals of the American Thoracic Society
Brian A Gordon, Tyler M Blazey, Jon Christensen, Aylin Dincer, Shaney Flores, Sarah Keefe, Charles Chen, Yi Su, Eric M McDade, Guoqiao Wang, Yan Li, Jason Hassenstab, Andrew Aschenbrenner, Russ Hornbeck, Clifford R Jack, Beau M Ances, Sarah B Berman, Jared R Brosch, Douglas Galasko, Serge Gauthier, James J Lah, Mario Masellis, Christopher H van Dyck, Mark A Mintun, Gregory Klein, Smiljana Ristic, Nigel J Cairns, Daniel S Marcus, Chengjie Xiong, David M Holtzman, Marcus E Raichle, John C Morris, Randall J Bateman, Tammie L S Benzinger
Tauopathy is a hallmark pathology of Alzheimer's disease with a strong relationship with cognitive impairment. As such, understanding tau may be a key to clinical interventions. In vivo tauopathy has been measured using cerebrospinal fluid assays, but these do not provide information about where pathology is in the brain. The introduction of PET ligands that bind to paired helical filaments provides the ability to measure the amount and distribution of tau pathology. The heritability of the age of dementia onset tied to the specific mutations found in autosomal dominant Alzheimer's disease families provides an elegant model to study the spread of tau across the course of the disease as well as the cross-modal relationship between tau and other biomarkers...
February 11, 2019: Brain: a Journal of Neurology
Sarah Kiff, Carolyn Babb, Maria Guemes, Antonia Dastamani, Clare Gilbert, Sarah E Flanagan, Sian Ellard, John Barton, M Dattani, Pratik Shah
We report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous ABCC8 mutation. A term baby, with birth weight 3.8 kg, born to consanguineous parents presented on day 1 of life with hypoglycaemia. Hypoglycaemia screen confirmed CHI. Diazoxide was commenced on day 7 due to ongoing elevated glucose requirements (15 mg/kg/min), but despite escalation to a maximum dose (15 mg/kg/day), intravenous (i.v.) glucose requirement remained high (13 mg/kg/min)...
February 11, 2019: Endocrinology, Diabetes & Metabolism Case Reports
Glenn Choon Lim Wong, Vipin Narang, Yanxia Lu, Xavier Camous, Ma Shwe Zin Nyunt, Christophe Carre, Chrystal Tan, Chin Hui Xian, Joni Chong, Michelle Chua, Wilson How, Esther Mok, Paul Tambyah, Michael Poidinger, Brian Abel, Nicolas Burdin, Laurence Quemeneur, Nabil Bosco, Tze Pin Ng, Anis Larbi
Physical inactivity is one of the leading contributors to worldwide morbidity and mortality. The elderly are particularly susceptible since the features of physical inactivity overlap with the outcomes of natural aging - including the propensity to develop cardiovascular diseases, cancer, diabetes mellitus, sarcopenia and cognitive impairment. The age-dependent loss of immune function, or immunosenescence, refers to the progressive depletion of primary immune resources and is linked to the development of many of these conditions...
2019: Exercise Immunology Review
Ryszard Pluta, Marzena Ułamek-Kozioł
In the aging world population, Alzheimer's disease accounts for more than 70% of all cases of dementia and is the sixth leading cause of death. The neurodegenerative processes of this disorder can begin 10-20 years before the clinical symptoms develop. Postmortem brain autopsy of Alzheimer's disease cases reveals characteristic hallmarks like extracellular amyloid plaques and intraneuronal neurofibrillary tangles and synaptic and neuronal disintegration with severe brain atrophy. Some studies have reported that platelets contain the amyloid protein precursor and the secretase enzymes required for the amyloidogenic processing of this protein...
2019: Advances in Experimental Medicine and Biology
Erik Boot, Anne S Bassett, Connie Marras
Background: 22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition associated with an increased risk of early-onset Parkinson's disease (PD). Methods: We review the clinical, neuroimaging, and neuropathological observations, as well as diagnostic challenges, of PD in 22q11.2DS. We conducted a search of PubMed up until June 1, 2018 and personal files to identify relevant publications. Results: 22q11.2DS-associated PD is responsible for approximately 0...
January 2019: Movement Disorders Clinical Practice
Arjun N Sasikumar, David W Killilea, Brian K Kennedy, Rachel B Brem
Lysosome function is compromised during aging and in many disease states. Interventions that promote lysosomal activity and acidification are thus of prime interest as treatments for longevity and health. Intracellular pH can be controlled by the exchange of protons for inorganic ions, and in cells from microbes to man, when potassium is restricted in the growth medium, the cytoplasm becomes acidified. Here we use a yeast model to show that potassium limited-cells exhibit hallmarks of increased acidity in the vacuole, the analog of the lysosome, and live long by a mechanism that requires the vacuolar machinery...
February 8, 2019: Experimental Gerontology
Evandro F Fang, Yujun Hou, Konstantinos Palikaras, Bryan A Adriaanse, Jesse S Kerr, Beimeng Yang, Sofie Lautrup, Md Mahdi Hasan-Olive, Domenica Caponio, Xiuli Dan, Paula Rocktäschel, Deborah L Croteau, Mansour Akbari, Nigel H Greig, Tormod Fladby, Hilde Nilsen, M Zameel Cader, Mark P Mattson, Nektarios Tavernarakis, Vilhelm A Bohr
Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+ supplementation, urolithin A, and actinonin) reverses memory impairment through PINK-1 (PTEN-induced kinase-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumor affecting-1)-dependent pathways...
February 11, 2019: Nature Neuroscience
Jun Hua, SeungWook Lee, Nicholas I S Blair, Michael Wyss, Jiri M G van Bergen, Simon J Schreiner, Sonja M Kagerer, Sandra E Leh, Anton F Gietl, Valerie Treyer, Alfred Buck, Roger M Nitsch, Klaas P Pruessmann, Hanzhang Lu, Peter C M Van Zijl, Marilyn Albert, Christoph Hock, Paul G Unschuld
The protracted accumulation of amyloid-β (Aβ) is a major pathologic hallmark of Alzheimer's disease and may trigger secondary pathological processes that include neurovascular damage. This study was aimed at investigating long-term effects of Aβ burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aβ burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years]...
January 10, 2019: Neurobiology of Aging
Young Soon Yoon, Minhee Jin, Don D Sin
Introduction The prevalence of chronic obstructive pulmonary disease (COPD) increases exponentially with aging. Its pathogenesis, however, is not well known and aside from smoking cessation, there are no disease-modifying treatments for this disease. Areas covered COPD is associated with accelerating aging and aging-related diseases. In this review, we will discuss the hallmarks of aging including genomic instability, telomere attrition, epigenetic alteration, loss of proteostasis, mitochondrial dysfunction, deregulated nutrient sensing, cellular senescence, stem cell exhaustion, and altered intercellular communication, which may be involved in COPD pathogenesis...
February 8, 2019: Expert Review of Respiratory Medicine
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