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Aging Cell

Dan Wang, Lei Hou, Shuhei Nakamura, Ming Su, Fang Li, Weiyang Chen, Yizhen Yan, Christopher D Green, Di Chen, Hong Zhang, Adam Antebi, Jing-Dong J Han
The RNA-binding protein LIN-28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin-28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN-28-regulated microRNA let-7 was required for these effects by targeting akt-1/2 and decreasing their protein levels. AKT-1/2 and the downstream DAF-16 transcription factor were both required for the lifespan and germline stem cell effects of lin-28...
October 11, 2016: Aging Cell
Elodie Martin, Céline Boucher, Bertrand Fontaine, Cécile Delarasse
Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid-β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte-derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in TgAPP/PS1 and TgAPP/PS1dE9, two transgenic AD mouse models, compared to WT littermates...
October 8, 2016: Aging Cell
Ane Wyssenbach, Tania Quintela, Francisco Llavero, Jose L Zugaza, Carlos Matute, Elena Alberdi
Astrogliosis is a hallmark of Alzheimer's disease (AD) and may constitute a primary pathogenic component of that disorder. Elucidation of signaling cascades inducing astrogliosis should help characterizing the function of astrocytes and identifying novel molecular targets to modulate AD progression. Here, we describe a novel mechanism by which soluble amyloid-β modulates β1-integrin activity and triggers NADPH oxidase (NOX)-dependent astrogliosis in vitro and in vivo. Amyloid-β oligomers activate a PI3K/classical PKC/Rac1/NOX pathway which is initiated by β1-integrin in cultured astrocytes...
October 5, 2016: Aging Cell
Magdalena Misiak, Rebeca Vergara Greeno, Beverly A Baptiste, Peter Sykora, Dong Liu, Stephanie Cordonnier, Evandro F Fang, Deborah L Croteau, Mark P Mattson, Vilhelm A Bohr
Alzheimer's disease (AD) involves the progressive degeneration of neurons critical for learning and memory. In addition, patients with AD typically exhibit impaired olfaction associated with neuronal degeneration in the olfactory bulb (OB). Because DNA base excision repair (BER) is reduced in brain cells during normal aging and AD, we determined whether inefficient BER due to reduced DNA polymerase-β (Polβ) levels renders OB neurons vulnerable to degeneration in the 3xTgAD mouse model of AD. We interrogated OB histopathology and olfactory function in wild-type and 3xTgAD mice with normal or reduced Polβ levels...
September 30, 2016: Aging Cell
Aneesa Ansari, Md Shahedur Rahman, Subbroto K Saha, Forhad K Saikot, Akash Deep, Ki-Hyun Kim
In mammals, seven members of the sirtuin protein family known as class III histone deacetylase have been identified for their characteristic features. These distinguished characteristics include the tissues where they are distributed or located, enzymatic activities, molecular functions, and involvement in diseases. Among the sirtuin members, SIRT3 has received much attention for its role in cancer genetics, aging, neurodegenerative disease, and stress resistance. SIRT3 controls energy demand during stress conditions such as fasting and exercise as well as metabolism through the deacetylation and acetylation of mitochondrial enzymes...
September 29, 2016: Aging Cell
David Desjardins, Briseida Cacho-Valadez, Ju-Ling Liu, Ying Wang, Callista Yee, Kristine Bernard, Arman Khaki, Lionel Breton, Siegfried Hekimi
Reactive oxygen species (ROS) are potentially toxic, but they are also signaling molecules that modulate aging. Recent observations that ROS can promote longevity have to be reconciled with the numerous claims about the benefits of antioxidants on lifespan. Here, three antioxidants [N-acetylcysteine (NAC), vitamin C, and resveratrol (RSV)] were tested on Caenorhabditis elegans mutants that alter drug uptake, mitochondrial function, and ROS metabolism. We observed that like pro-oxidants, antioxidants can both lengthen and shorten lifespan, dependent on concentration, genotypes, and conditions...
September 28, 2016: Aging Cell
Alexander M Kulminski, Yelena Kernogitski, Irina Culminskaya, Yury Loika, Konstantin G Arbeev, Olivia Bagley, Matt Duan, Liubov Arbeeva, Svetlana V Ukraintseva, Deqing Wu, Eric Stallard, Anatoliy I Yashin
Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age-related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogeneous, age-related traits driven by the elusive role of evolution in their properties. We analyzed in detail the associations of rs693 and rs562338 polymorphisms representing the Apolipoprotein B locus with endophenotypes (total cholesterol [TC] and high-density lipoprotein cholesterol) and phenotypes (myocardial infarction [MI] and survival) in four large-scale studies, which include 20 748 individuals with 2357 MI events...
September 28, 2016: Aging Cell
Thibaud Mathis, Michael Housset, Chiara Eandi, Fanny Beguier, Sara Touhami, Sacha Reichman, Sebastien Augustin, Pauline Gondouin, José-Alain Sahel, Laurent Kodjikian, Olivier Goureau, Xavier Guillonneau, Florian Sennlaub
Orthodenticle homeobox 2 (OTX2) controls essential, homeostatic retinal pigment epithelial (RPE) genes in the adult. Using cocultures of human CD14(+) blood monocytes (Mos) and primary porcine RPE cells and a fully humanized system using human-induced pluripotent stem cell-derived RPE cells, we show that activated Mos markedly inhibit RPEOTX2 expression and resist elimination in contact with the immunosuppressive RPE. Mechanistically, we demonstrate that TNF-α, secreted from activated Mos, mediates the downregulation of OTX2 and essential RPE genes of the visual cycle among others...
September 22, 2016: Aging Cell
Lisa A Lesniewski, Douglas R Seals, Ashley E Walker, Grant D Henson, Mark W Blimline, Daniel W Trott, Gary C Bosshardt, Thomas J LaRocca, Brooke R Lawson, Melanie C Zigler, Anthony J Donato
Inhibition of mammalian target of rapamycin, mTOR, extends lifespan and reduces age-related disease. It is not known what role mTOR plays in the arterial aging phenotype or if mTOR inhibition by dietary rapamycin ameliorates age-related arterial dysfunction. To explore this, young (3.8 ± 0.6 months) and old (30.3 ± 0.2 months) male B6D2F1 mice were fed a rapamycin supplemented or control diet for 6-8 weeks. Although there were few other notable changes in animal characteristics after rapamycin treatment, we found that glucose tolerance improved in old mice, but was impaired in young mice, after rapamycin supplementation (both P < 0...
September 22, 2016: Aging Cell
Ryan T Wu, Lei Cao, Elliot Mattson, Kenneth W Witwer, Jay Cao, Huawei Zeng, Xin He, Gerald F Combs, Wen-Hsing Cheng
Selenium (Se) is a trace metalloid essential for life, but its nutritional and physiological roles during the aging process remain elusive. While telomere attrition contributes to replicative senescence mainly through persistent DNA damage response, such an aging process is mitigated in mice with inherently long telomeres. Here, weanling third generation telomerase RNA component knockout mice carrying short telomeres were fed a Se-deficient basal diet or the diet supplemented with 0.15 ppm Se as sodium selenate to be nutritionally sufficient throughout their life...
September 21, 2016: Aging Cell
Mahesh Shivarama Shetty, Mahima Sharma, Sreedharan Sajikumar
Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear...
September 16, 2016: Aging Cell
Jong-Chan Park, Sung Hoon Baik, Sun-Ho Han, Hyun Jin Cho, Hyunjung Choi, Haeng Jun Kim, Heesun Choi, Wonik Lee, Dong Kyu Kim, Inhee Mook-Jung
The blood-brain barrier (BBB) is composed of brain capillary endothelial cells and has an important role in maintaining homeostasis of the brain separating the blood from the parenchyma of the central nervous system (CNS). It is widely known that disruption of the BBB occurs in various neurodegenerative diseases, including Alzheimer's disease (AD). Annexin A1 (ANXA1), an anti-inflammatory messenger, is expressed in brain endothelial cells and regulates the BBB integrity. However, its role and mechanism for protecting BBB in AD have not been identified...
September 16, 2016: Aging Cell
Nadezhda V Petrova, Artem K Velichko, Sergey V Razin, Omar L Kantidze
To date, dozens of stress-induced cellular senescence phenotypes have been reported. These cellular senescence states may differ substantially from each other, as well as from replicative senescence through the presence of specific senescence features. Here, we attempted to catalog virtually all of the cellular senescence-like states that can be induced by low molecular weight compounds. We summarized biological markers, molecular pathways involved in senescence establishment, and specific traits of cellular senescence states induced by more than fifty small molecule compounds...
September 14, 2016: Aging Cell
Takamasa Ishii, Yumi Takanashi, Koichi Sugita, Masaki Miyazawa, Rintaro Yanagihara, Kayo Yasuda, Hiromi Onouchi, Noboru Kawabe, Munehiro Nakata, Yorihiro Yamamoto, Phil S Hartman, Naoaki Ishii
The etiology of astrocyte dysfunction is not well understood even though neuronal defects have been extensively studied in a variety of neuronal degenerative diseases. Astrocyte defects could be triggered by the oxidative stress that occurs during physiological aging. Here, we provide evidence that intracellular or mitochondrial reactive oxygen species (ROS) at physiological levels can cause hippocampal (neuronal) dysfunctions. Specifically, we demonstrate that astrocyte defects occur in the hippocampal area of middle-aged Tet-mev-1 mice with the SDHC(V69E) mutation...
September 13, 2016: Aging Cell
Ignacio Amigo, Sergio Luiz Menezes-Filho, Luis Alberto Luévano-Martínez, Bruno Chausse, Alicia J Kowaltowski
Caloric restriction (CR) protects against many cerebral pathological conditions that are associated with excitotoxic damage and calcium overload, although the mechanisms are still poorly understood. Here we show that CR strongly protects against excitotoxic insults in vitro and in vivo in a manner associated with significant changes in mitochondrial function. CR increases electron transport chain activity, enhances antioxidant defenses, and favors mitochondrial calcium retention capacity in the brain. These changes are accompanied by a decrease in cyclophilin D activity and acetylation and an increase in Sirt3 expression...
September 13, 2016: Aging Cell
Graham Dominick, Jacqueline Bowman, Xinna Li, Richard A Miller, Gonzalo G Garcia
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long-lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The ways in which lower mTOR signals slow aging and age-related diseases are, however, not well characterized...
September 13, 2016: Aging Cell
Vicki Chrysostomou, Sandra Galic, Peter van Wijngaarden, Ian A Trounce, Gregory R Steinberg, Jonathan G Crowston
Retinal ganglion cells (RGCs) become increasingly vulnerable to injury with advancing age. We recently showed that this vulnerability can be strongly modified in mice by exercise. However, the characteristics and underlying mechanisms of retinal protection with exercise remain unknown. Hence, the aim of this study was to investigate cellular changes associated with exercise-induced protection of aging retinal cells and the role of local and peripheral trophic signalling in mediating these effects. We focussed on two molecules that are thought to play key roles in mediating beneficial effects of exercise: brain-derived neurotrophic factor (BDNF) and AMP-activated protein kinase (AMPK)...
September 9, 2016: Aging Cell
Hui Wang, Limin Han, Ganye Zhao, Hong Shen, Pengfeng Wang, Zhaomeng Sun, Chenzhong Xu, Yuanyuan Su, Guodong Li, Tanjun Tong, Jun Chen
Senescent cells display a senescence-associated secretory phenotype (SASP) which contributes to tumor suppression, aging, and cancer. However, the underlying mechanisms for SASP regulation are not fully elucidated. SIRT1, a nicotinamide adenosine dinucleotide-dependent deacetylase, plays multiple roles in metabolism, inflammatory response, and longevity, etc. However, its posttranscriptional regulation and its roles in cellular senescence and SASP regulation are still elusive. Here, we identify the RNA-binding protein hnRNP A1 as a posttranscriptional regulator of SIRT1, as well as cell senescence and SASP regulator...
September 9, 2016: Aging Cell
Loic Verlingue, Aurélien Dugourd, Gautier Stoll, Emmanuel Barillot, Laurence Calzone, Arturo Londoño-Vallejo
Altered molecular responses to insulin and growth factors (GF) are responsible for late-life shortening diseases such as type-2 diabetes mellitus (T2DM) and cancers. We have built a network of the signaling pathways that control S-phase entry and a specific type of senescence called geroconversion. We have translated this network into a Boolean model to study possible cell phenotype outcomes under diverse molecular signaling conditions. In the context of insulin resistance, the model was able to reproduce the variations of the senescence level observed in tissues related to T2DM's main morbidity and mortality...
September 9, 2016: Aging Cell
Evie van der Spoel, Steffy W Jansen, Abimbola A Akintola, Bart E Ballieux, Christa M Cobbaert, P Eline Slagboom, Gerard Jan Blauw, Rudi G J Westendorp, Hanno Pijl, Ferdinand Roelfsema, Diana van Heemst
Reduced growth hormone (GH) signaling has been consistently associated with increased health and lifespan in various mouse models. Here, we assessed GH secretion and its control in relation with human familial longevity. We frequently sampled blood over 24 h in 19 middle-aged offspring of long-living families from the Leiden Longevity Study together with 18 of their partners as controls. Circulating GH concentrations were measured every 10 min and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) every 4 h...
September 7, 2016: Aging Cell
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