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Aging Cell

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https://www.readbyqxmd.com/read/30003692/in-vivo-gdf3-administration-abrogates-aging-related-muscle-regeneration-delay-following-acute-sterile-injury
#1
Andreas Patsalos, Zoltan Simandi, Tristan T Hays, Matthew Peloquin, Matine Hajian, Isabella Restrepo, Paul M Coen, Alan J Russell, Laszlo Nagy
Tissue regeneration is a highly coordinated process with sequential events including immune cell infiltration, clearance of damaged tissues, and immune-supported regrowth of the tissue. Aging has a well-documented negative impact on this process globally; however, whether changes in immune cells per se are contributing to the decline in the body's ability to regenerate tissues with aging is not clearly understood. Here, we set out to characterize the dynamics of macrophage infiltration and their functional contribution to muscle regeneration by comparing young and aged animals upon acute sterile injury...
July 12, 2018: Aging Cell
https://www.readbyqxmd.com/read/30003683/ccar-1-is-a-negative-regulator-of-the-heat-shock-response-in-caenorhabditis-elegans
#2
Jessica Brunquell, Rachel Raynes, Philip Bowers, Stephanie Morris, Alana Snyder, Doreen Lugano, Andrew Deonarine, Sandy D Westerheide
Defects in protein quality control during aging are central to many human diseases, and strategies are needed to better understand mechanisms of controlling the quality of the proteome. The heat-shock response (HSR) is a conserved survival mechanism mediated by the transcription factor HSF1 which functions to maintain proteostasis. In mammalian cells, HSF1 is regulated by a variety of factors including the prolongevity factor SIRT1. SIRT1 promotes the DNA-bound state of HSF1 through deacetylation of the DNA-binding domain of HSF1, thereby enhancing the HSR...
July 12, 2018: Aging Cell
https://www.readbyqxmd.com/read/30003673/proper-splicing-contributes-to-visual-function-in-the-aging-drosophila-eye
#3
Rachel Stegeman, Hana Hall, Spencer E Escobedo, Henry C Chang, Vikki M Weake
Changes in splicing patterns are a characteristic of the aging transcriptome; however, it is unclear whether these age-related changes in splicing facilitate the progressive functional decline that defines aging. In Drosophila, visual behavior declines with age and correlates with altered gene expression in photoreceptors, including downregulation of genes encoding splicing factors. Here, we characterized the significance of these age-regulated splicing-associated genes in both splicing and visual function...
July 12, 2018: Aging Cell
https://www.readbyqxmd.com/read/30003648/monoamine-oxidase-a-is-a-novel-driver-of-stress-induced-premature-senescence-through-inhibition-of-parkin-mediated-mitophagy
#4
Nicola Manzella, Yohan Santin, Damien Maggiorani, Hélène Martini, Victorine Douin-Echinard, Joao F Passos, Frank Lezoualc'h, Claudia Binda, Angelo Parini, Jeanne Mialet-Perez
Cellular senescence, the irreversible cell cycle arrest observed in somatic cells, is an important driver of age-associated diseases. Mitochondria have been implicated in the process of senescence, primarily because they are both sources and targets of reactive oxygen species (ROS). In the heart, oxidative stress contributes to pathological cardiac ageing, but the mechanisms underlying ROS production are still not completely understood. The mitochondrial enzyme monoamine oxidase-A (MAO-A) is a relevant source of ROS in the heart through the formation of H2 O2 derived from the degradation of its main substrates, norepinephrine (NE) and serotonin...
July 12, 2018: Aging Cell
https://www.readbyqxmd.com/read/29992704/plasma-proteomic-signature-of-age-in-healthy-humans
#5
Toshiko Tanaka, Angelique Biancotto, Ruin Moaddel, Ann Zenobia Moore, Marta Gonzalez-Freire, Miguel A Aon, Julián Candia, Pingbo Zhang, Foo Cheung, Giovanna Fantoni, Richard D Semba, Luigi Ferrucci
To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22-93 years old, who were disease- and treatment-free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10-5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0...
July 11, 2018: Aging Cell
https://www.readbyqxmd.com/read/29992743/vcam-1-upregulation-accompanies-muscle-remodeling-following-resistance-type-exercise-in-snell-dwarf-pit1-dw-dw-mice
#6
Erik P Rader, Marshall A Naimo, James Ensey, Brent A Baker
Snell dwarf mice (Pit1dw/dw ) exhibit deficiencies in growth hormone, prolactin, and thyroid stimulating hormone. Besides being an experimental model of hypopituitarism, these mice are long-lived (>40% lifespan extension) and utilized as a model of slowed/delayed aging. Whether this longevity is accompanied by a compromised quality of life in terms of muscular performance has not yet been characterized. In this study, we investigated nontrained and trained muscles 1 month following a general validated resistance-type exercise protocol in 3-month-old Snell dwarf mice and control littermates...
July 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29992725/the-emerging-roles-of-protein-homeostasis-governing-pathways-in-alzheimer-s-disease
#7
REVIEW
Ji Cheng, Brian J North, Tao Zhang, Xiangpeng Dai, Kaixiong Tao, Jianping Guo, Wenyi Wei
Pathways governing protein homeostasis are involved in maintaining the structural, quantitative, and functional stability of intracellular proteins and involve the ubiquitin-proteasome system, autophagy, endoplasmic reticulum, and mTOR pathway. Due to the broad physiological implications of protein homeostasis pathways, dysregulation of proteostasis is often involved in the development of multiple pathological conditions, including Alzheimer's disease (AD). Similar to other neurodegenerative diseases that feature pathogenic accumulation of misfolded proteins, Alzheimer's disease is characterized by two pathological hallmarks, amyloid-β (Aβ) plaques and tau aggregates...
July 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29963746/foxo-are-required-for-intervertebral-disk-homeostasis-during-aging-and-their-deficiency-promotes-disk-degeneration
#8
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Kohei Miyata, Sho Mokuda, Daisuke Sakai, Koichi Masuda, Hiroshi Asahara, Martin K Lotz
Intervertebral disk (IVD) degeneration is a prevalent age-associated musculoskeletal disorder and a major cause of chronic low back pain. Aging is the main risk factor for the disease, but the molecular mechanisms regulating IVD homeostasis during aging are unknown. The aim of this study was to investigate the function of FOXO, a family of transcription factors linked to aging and longevity, in IVD aging and age-related degeneration. Conditional deletion of all FOXO isoforms (FOXO1, 3, and 4) in IVD using the Col2a1Cre and AcanCreER mouse resulted in spontaneous development of IVD degeneration that was driven by severe cell loss in the nucleus pulposus (NP) and cartilaginous endplates (EP)...
July 2, 2018: Aging Cell
https://www.readbyqxmd.com/read/29963744/aging-and-alzheimer-s-disease-comparison-and-associations-from-molecular-to-system-level
#9
REVIEW
Xian Xia, Quanlong Jiang, Joseph McDermott, Jing-Dong J Han
Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level...
July 2, 2018: Aging Cell
https://www.readbyqxmd.com/read/29963742/systems-pathology-analysis-identifies-neurodegenerative-nature-of-age-related-vitreoretinal-interface-diseases
#10
Tiina Öhman, Fitsum Tamene, Helka Göös, Sirpa Loukovaara, Markku Varjosalo
Aging is a phenomenon that is associated with profound medical implications. Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision-threatening vitreoretinal diseases affecting millions of aging people globally, making these conditions an important public health issue. iERM is characterized by fibrous tissue developing on the surface of the macula, which leads to biomechanical and biochemical macular damage. MH is a small breakage in the macula and is associated with many ocular conditions...
July 2, 2018: Aging Cell
https://www.readbyqxmd.com/read/29959820/gene-expression-based-drug-repurposing-to-target-ageing
#11
Handan Melike Dönertaş, Matías Fuentealba Valenzuela, Linda Partridge, Janet M Thornton
Ageing is the largest risk factor for a variety of non-communicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both life- and health-span. Ageing is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the discovery of new pharmacological candidates to ameliorate its effects. In this study, instead of a target-centric approach, we adopt a systems level drug repurposing methodology to discover drugs that could combat ageing in human brain...
June 30, 2018: Aging Cell
https://www.readbyqxmd.com/read/29943496/role-of-dietary-amino-acid-balance-in-diet-restriction-mediated-lifespan-extension-renoprotection-and-muscle-weakness-in-aged-mice
#12
Shohei Yoshida, Kosuke Yamahara, Shinji Kume, Daisuke Koya, Mako Yasuda-Yamahara, Naoko Takeda, Norihisa Osawa, Masami Chin-Kanasaki, Yusuke Adachi, Kenji Nagao, Hiroshi Maegawa, Shin-Ichi Araki
Extending healthy lifespan is an emerging issue in an aging society. This study was designed to identify a dietary method of extending lifespan, promoting renoprotection, and preventing muscle weakness in aged mice, with a focus on the importance of the balance between dietary essential (EAAs) and nonessential amino acids (NEAAs) on the dietary restriction (DR)-induced antiaging effect. Groups of aged mice were fed ad libitum, a simple DR, or a DR with recovering NEAAs or EAAs. Simple DR significantly extended lifespan and ameliorated age-related kidney injury; however, the beneficial effects of DR were canceled by recovering dietary EAA but not NEAA...
June 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29943484/differential-aging-related-changes-in-neurophysiology-and-gene-expression-in-ib4-positive-and-ib4-negative-nociceptive-neurons
#13
Malgorzata A Mis, Mark F Rogers, Aaron R Jeffries, Anna L Wilbrey, Lubin Chen, Yang Yang, Sulayman Dib-Hajj, Stephen G Waxman, Edward B Stevens, Andrew D Randall
Despite pain prevalence altering with age, the effects of aging on the properties of nociceptors are not well understood. Nociceptors, whose somas are located in dorsal root ganglia, are frequently divided into two groups based on their ability to bind isolectin B4 (IB4). Here, using cultured neurons from 1-, 3-, 5-, 8-, 12-, and 18-month-old mice, we investigate age-dependent changes in IB4-positive and IB4-negative neurons. Current-clamp experiments at physiological temperature revealed nonlinear changes in firing frequency of IB4-positive, but not IB4-negative neurons, with a peak at 8 months...
June 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29943428/spontaneous-development-of-alzheimer-s-disease-associated-brain-pathology-in-a-shugoshin-1-mouse-cohesinopathy-model
#14
Chinthalapally V Rao, Mudassir Farooqui, Yuting Zhang, Adam S Asch, Hiroshi Y Yamada
Spontaneous late-onset Alzheimer's disease (LOAD) accounts for more than 95% of all human AD. As mice do not normally develop AD and as understanding on molecular processes leading to spontaneous LOAD has been insufficient to successfully model LOAD in mouse, no mouse model for LOAD has been available. Existing mouse AD models are all early-onset AD (EOAD) models that rely on forcible expression of AD-associated protein(s), which may not recapitulate prerequisites for spontaneous LOAD. This limitation in AD modeling may contribute to the high failure rate of AD drugs in clinical trials...
June 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29923368/human-electronegative-ldl-induces-mitochondrial-dysfunction-and-premature-senescence-of-vascular-cells-in-vivo
#15
Yu-Chen Wang, An-Sheng Lee, Long-Sheng Lu, Liang-Yin Ke, Wei-Yu Chen, Jian-Wen Dong, Jonathan Lu, Zhenping Chen, Chih-Sheng Chu, Hua-Chen Chan, Taha Y Kuzan, Ming-Hsien Tsai, Wen-Li Hsu, Richard A F Dixon, Tatsuya Sawamura, Kuan-Cheng Chang, Chu-Huang Chen
Dysregulation of plasma lipids is associated with age-related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low-density lipoprotein (LDL), induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg-1  day-1 ) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence-associated β-galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5-treated but not L1-treated mice...
June 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29901258/overexpression-of-nmnat3-efficiently-increases-nad-and-ngd-levels-and-ameliorates-age-associated-insulin-resistance
#16
Maryam Gulshan, Keisuke Yaku, Keisuke Okabe, Arshad Mahmood, Tsutomu Sasaki, Masashi Yamamoto, Keisuke Hikosaka, Isao Usui, Tadahiro Kitamura, Kazuyuki Tobe, Takashi Nakagawa
Nicotinamide adenine dinucleotide (NAD) is an important cofactor that regulates various biological processes, including metabolism and gene expression. As a coenzyme, NAD controls mitochondrial respiration through enzymes of the tricarboxylic acid (TCA) cycle, β-oxidation, and oxidative phosphorylation and also serves as a substrate for posttranslational protein modifications, such as deacetylation and ADP-ribosylation by sirtuins and poly(ADP-ribose) polymerase (PARP), respectively. Many studies have demonstrated that NAD levels decrease with aging and that these declines cause various aging-associated diseases...
June 14, 2018: Aging Cell
https://www.readbyqxmd.com/read/29896785/microrna-31a-5p-from-aging-bmscs-links-bone-formation-and-resorption-in-the-aged-bone-marrow-microenvironment
#17
Rongyao Xu, Xiang Shen, Yameng Si, Yu Fu, Weiwen Zhu, Tao Xiao, Zongyun Fu, Ping Zhang, Jie Cheng, Hongbing Jiang
The alteration of age-related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age-related bone loss. Here, we observed that the level of microRNA-31a-5p (miR-31a-5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness...
June 12, 2018: Aging Cell
https://www.readbyqxmd.com/read/29888494/mitochondria-and-aging-a-role-for-the-mitochondrial-transition-pore
#18
REVIEW
Mathieu Panel, Bijan Ghaleh, Didier Morin
The cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging...
June 11, 2018: Aging Cell
https://www.readbyqxmd.com/read/29882317/glucocorticoid-mediated-modulation-of-morphological-changes-associated-with-aging-in-microglia
#19
Lynn van Olst, Pascal Bielefeld, Carlos P Fitzsimons, Helga E de Vries, Marijn Schouten
Microglia dynamically adapt their morphology and function during increasing age. However, the mechanisms behind these changes are to date poorly understood. Glucocorticoids (GCs) are long known and utilized for their immunomodulatory actions and endogenous GC levels are described to alter with advancing age. We here tested the hypothesis that age-associated elevations in GC levels implicate microglia function and morphology. Our data indicate a decrease in microglial complexity and a concomitant increase in GC levels during aging...
June 7, 2018: Aging Cell
https://www.readbyqxmd.com/read/29877034/impaired-ampa-signaling-and-cytoskeletal-alterations-induce-early-synaptic-dysfunction-in-a-mouse-model-of-alzheimer-s-disease
#20
David Baglietto-Vargas, Gilberto Aleph Prieto, Agenor Limon, Stefania Forner, Carlos J Rodriguez-Ortiz, Kenji Ikemura, Rahasson R Ager, Rodrigo Medeiros, Laura Trujillo-Estrada, Alessandra C Martini, Masashi Kitazawa, Jose C Davila, Carl W Cotman, Antonia Gutierrez, Frank M LaFerla
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that impairs memory and causes cognitive and psychiatric deficits. New evidences indicate that AD is conceptualized as a disease of synaptic failure, although the molecular and cellular mechanisms underlying these defects remain to be elucidated. Determining the timing and nature of the early synaptic deficits is critical for understanding the progression of the disease and for identifying effective targets for therapeutic intervention. Using single-synapse functional and morphological analyses, we find that AMPA signaling, which mediates fast glutamatergic synaptic transmission in the central nervous system (CNS), is compromised early in the disease course in an AD mouse model...
June 6, 2018: Aging Cell
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