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Cellular aging dynamics after acute malaria infection: A 12 ‐month longitudinal study
Summary Accelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. Telomere length was measured using real‐time quantitative PCR, while telomerase activity and CDKN2A expression were meas...
Source: Aging Cell - November 16, 2017 Category: Cytology Authors: Muhammad Asghar, Victor Yman, Manijeh Vafa Homann, Klara Sond én, Ulf Hammar, Dennis Hasselquist, Anna Färnert Tags: ORIGINAL ARTICLE Source Type: research

SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease
The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. SIRT3 mRNA and protein levels were significantly decreased in AD cerebral cortex, and Ac‐p53 K320 was significantly increased in AD mitochondria. SIRT3 prevented p53‐induced mitochondrial dysfunction and neuronal damage in a deacetylase activity‐dependent manner. Notably, mitochondrially targeted p53 (mito‐p53) directly reduced mitochondria DNA‐encoded ND2 and ND4 gene expression resulting in increased reactive oxygen species (ROS) and reduced mitochondrial oxygen consumption....
Source: Aging Cell - November 11, 2017 Category: Cytology Authors: Junghee Lee, Yunha Kim, Tian Liu, Yu Jin Hwang, Seung Jae Hyeon, Hyeonjoo Im, Kyungeun Lee, Victor E. Alvarez, Ann C. McKee, Soo ‐Jong Um, Manwook Hur, Inhee Mook‐Jung, Neil W. Kowall, Hoon Ryu Tags: Original Article Source Type: research

Running ‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism
Summary Loss of mitochondrial respiratory flux is a hallmark of skeletal muscle aging, contributing to a progressive decline of muscle strength. Endurance exercise alleviates the decrease in respiratory flux, both in humans and in rodents. Here, we dissect the underlying mechanism of mitochondrial flux decline by integrated analysis of the molecular network. Mice were given a lifelong ad libitum low‐fat or high‐fat sucrose diet and were further divided into sedentary and running‐wheel groups. At 6, 12, 18 and 24 months, muscle weight, triglyceride content and mitochondrial respiratory flux were analysed. Su...
Source: Aging Cell - November 9, 2017 Category: Cytology Authors: Sarah Stolle, Jolita Ciapaite, Aaffien C. Reijne, Alzbeta Talarovicova, Justina C. Wolters, Ra úl Aguirre‐Gamboa, Pieter Vlies, Kim Lange, Pieter B. Neerincx, Gerben Vries, Patrick Deelen, Morris A. Swertz, Yang Li, Rainer Bischoff, Hjalmar P. Permenti Tags: ORIGINAL ARTICLE Source Type: research

Ketone body 3 ‐hydroxybutyrate mimics calorie restriction via the Nrf2 activator, fumarate, in the retina
Summary Calorie restriction (CR) being the most robust dietary intervention provides various health benefits. D‐3‐hydroxybutyrate (3HB), a major physiological ketone, has been proposed as an important endogenous molecule for CR. To investigate the role of 3HB in CR, we investigated potential shared mechanisms underlying increased retinal 3HB induced by CR and exogenously applied 3HB without CR to protect against ischemic retinal degeneration. The repeated elevation of retinal 3HB, with or without CR, suppressed retinal degeneration. Metabolomic analysis showed that the antioxidant pentose phosphate pathway and its limi...
Source: Aging Cell - November 9, 2017 Category: Cytology Authors: Yusuke Izuta, Toshihiro Imada, Ryuji Hisamura, Erina Oonishi, Shigeru Nakamura, Emi Inagaki, Masataka Ito, Tomoyoshi Soga, Kazuo Tsubota Tags: ORIGINAL ARTICLE Source Type: research

(Source: Aging Cell)
Source: Aging Cell - November 8, 2017 Category: Cytology Tags: Corrigendum Source Type: research

Issue Information
(Source: Aging Cell)
Source: Aging Cell - November 8, 2017 Category: Cytology Tags: Issue Information Source Type: research

PGC ‐1α affects aging‐related changes in muscle and motor function by modulating specific exercise‐mediated changes in old mice
Summary The age‐related impairment in muscle function results in a drastic decline in motor coordination and mobility in elderly individuals. Regular physical activity is the only efficient intervention to prevent and treat this age‐associated degeneration. However, the mechanisms that underlie the therapeutic effect of exercise in this context remain unclear. We assessed whether endurance exercise training in old age is sufficient to affect muscle and motor function. Moreover, as muscle peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) is a key regulatory hub in endurance exerc...
Source: Aging Cell - October 25, 2017 Category: Cytology Authors: Jonathan F. Gill, Gesa Santos, Svenia Schnyder, Christoph Handschin Tags: ORIGINAL ARTICLE Source Type: research

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene ‐induced lung tumors in aged mice
Summary Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3–5 months) and old (19–24 months) mice. Activation of KrasG12D in old mice resulted in shorter survival and development of higher‐grade lung tumors. Six weeks after KrasG12D activation, old lung tissues contained higher numbers of adenomas than their young tissue counterparts. Lung tumors in old mice displayed higher proliferation rates, as wel...
Source: Aging Cell - October 18, 2017 Category: Cytology Authors: Neha Parikh, Ryan L. Shuck, Mihai Gagea, Lanlan Shen, Lawrence A. Donehower Tags: Original Article Source Type: research

Age ‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits
Summary Recent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P 
Source: Aging Cell - October 17, 2017 Category: Cytology Authors: Tianxiao Huan, George Chen, Chunyu Liu, Anindya Bhattacharya, Jian Rong, Brian H. Chen, Sudha Seshadri, Kahraman Tanriverdi, Jane E. Freedman, Martin G. Larson, Joanne M. Murabito, Daniel Levy Tags: Original Article Source Type: research

Ghrelin deletion protects against age ‐associated hepatic steatosis by downregulating the C/EBPα‐p300/DGAT1 pathway
In conclusion, these studies demonstrate the mechanism by which ghrelin deletion prevents age‐associated hepatic steatosis and suggest that targeting this pathway may offer therapeutic benefit for NAFLD. (Source: Aging Cell)
Source: Aging Cell - October 12, 2017 Category: Cytology Authors: Bobby Guillory, Nicole Jawanmardi, Polina Iakova, Barbara Anderson, Pu Zang, Nikolai A. Timchenko, Jose M. Garcia Tags: Original Article Source Type: research

Interplay of pathogenic forms of human tau with different autophagic pathways
In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone‐mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this age‐related disease. We have found that the pathogenic P301L mutation inhibits degradation of tau by any of the three autophagic pathways, whereas the risk‐associated tau mutation A152T reroutes tau for degradation through a different autophagy pathway. We also found defective autophagic degradation of tau when using mutations that mimic common posttranslational modifications in ta...
Source: Aging Cell - October 12, 2017 Category: Cytology Authors: Benjamin Caballero, Yipeng Wang, Antonio Diaz, Inmaculada Tasset, Yves Robert Juste, Eva ‐Maria Mandelkow, Eckhard Mandelkow, Ana Maria Cuervo Tags: Original Article Source Type: research

Age ‐associated dysregulation of protein metabolism in the mammalian oocyte
We examined key nucleolar markers, including upstream binding transcription factor (UBTF), an RNA polymerase I cofactor, and fibrillarin, an rRNA methyltransferase. In oocytes from mice of advanced reproductive age, UBTF was primarily expressed in giant fibrillar centers (GFCs), structures associated with high levels of rDNA transcription, and fibrillarin expression was increased ~2‐fold. At the ultrastructural level, oocyte nucleoli from reproductively old mice had correspondingly more prominent fibrillar centers and dense fibrillar centers relative to young controls and more ribosomes were found in the cytoplasm. Taken...
Source: Aging Cell - October 10, 2017 Category: Cytology Authors: Francesca E. Duncan, Susmita Jasti, Ariel Paulson, John M. Kelsh, Barbara Fegley, Jennifer L. Gerton Tags: Original Article Source Type: research

Brain 5 ‐lipoxygenase over‐expression worsens memory, synaptic integrity, and tau pathology in the P301S mice
Summary Progressive accumulation of highly phosphorylated tau protein isoforms is the main feature of a group of neurodegenerative diseases collectively called tauopathies. Data from human and animal models of these diseases have shown that neuroinflammation often accompanies their pathogenesis. The 5‐lipoxygenase (5LO) is an enzyme widely expressed in the brain and a source of potent pro‐inflammatory mediators, while its pharmacological inhibition modulates the phenotype of a tau transgenic mouse model, the htau mice. By employing an adeno‐associated viral vector system to over‐express 5LO in the brain, we examine...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Alana N. Vagnozzi, Phillip F. Giannopoulos, Domenico Pratic ò Tags: Original Article Source Type: research

Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type ‐1 insulin‐like growth factor receptors in neuronal cells
Summary Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of β‐amyloid (Aβ), and neuronal loss. The self‐association of Aβ monomers into soluble oligomers seems to be crucial for the development of neurotoxicity (J. Neurochem., 00, 2007 and 1172). Aβ oligomers have been suggested to compromise neuronal functions in AD by reducing the expression levels of the CREB target gene and brain‐derived neurotrophic factor (BDNF) (J. Neurosci., 27, 2007 and 2628; Neurobiol. Aging, 36, 2015 and 20406 Mol. Neurodegener., 6, 2011...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Stefania Zimbone, Irene Monaco, Fiorenza Gian ì, Giuseppe Pandini, Agata G. Copani, Maria Laura Giuffrida, Enrico Rizzarelli Tags: Original Article Source Type: research

Sirt2 ‐BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality
Summary The level of Sirt2 protein is reduced in oocytes from aged mice, while exogenous expression of Sirt2 could ameliorate the maternal age‐associated meiotic defects. To date, the underlying mechanism remains unclear. Here, we confirmed that specific depletion of Sirt2 disrupts maturational progression and spindle/chromosome organization in mouse oocytes, with compromised kinetochore–microtubule attachments. Candidate screening revealed that acetylation state of lysine 243 on BubR1 (BubR1‐K243, an integral part of the spindle assembly checkpoint complex) functions during oocyte meiosis, and acetylation‐mime...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Danhong Qiu, Xiaojing Hou, Longsen Han, Xiaoyan Li, Juan Ge, Qiang Wang Tags: ORIGINAL ARTICLE Source Type: research

Influence of cell distribution and diabetes status on the association between mitochondrial DNA copy number and aging phenotypes in the InCHIANTI study
Summary Mitochondrial DNA copy number (mtDNA‐CN) estimated in whole blood is a novel marker of mitochondrial mass and function that can be used in large population‐based studies. Analyses that attempt to relate mtDNA‐CN to specific aging phenotypes may be confounded by differences in the distribution of blood cell types across samples. Also, low or high mtDNA‐CN may have a different meaning given the presence of diseases associated with mitochondrial damage. We evaluated the impact of blood cell type distribution and diabetes status on the association between mtDNA‐CN and aging phenotypes, namely chronologic age,...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Ann Zenobia Moore, Jun Ding, Marcus A. Tuke, Andrew R. Wood, Stefania Bandinelli, Timothy M. Frayling, Luigi Ferrucci Tags: Short Take Source Type: research

Anti ‐inflammaging effects of human alpha‐1 antitrypsin
Summary Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of geneti...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Ye Yuan, Benedetto DiCiaccio, Ying Li, Ahmed S. Elshikha, Denis Titov, Brian Brenner, Lee Seifer, Hope Pan, Nurdina Karic, Mohammad A. Akbar, Yuanqing Lu, Sihong Song, Lei Zhou Tags: Original Article Source Type: research

Human CD8+ EMRA T cells display a senescence ‐associated secretory phenotype regulated by p38 MAPK
Summary Cellular senescence is accompanied by a senescence‐associated secretory phenotype (SASP). We show here that primary human senescent CD8+ T cells also display a SASP comprising chemokines, cytokines and extracellular matrix remodelling proteases that are unique to this subset and contribute to age‐associated inflammation. We found the CD8+ CD45RA+CD27− EMRA subset to be the most heterogeneous, with a population aligning with the naïve T cells and another with a closer association to the effector memory subset. However, despite the differing processes that give rise to these senescent CD8+ T cells once...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Lauren A. Callender, Elizabeth C. Carroll, Robert W. J. Beal, Emma S. Chambers, Sussan Nourshargh, Arne N. Akbar, Sian M. Henson Tags: Original Article Source Type: research

In vivo properties of the disaggregase function of J ‐proteins and Hsc70 in Caenorhabditis elegans stress and aging
Summary Protein aggregation is enhanced upon exposure to various stress conditions and aging, which suggests that the quality control machinery regulating protein homeostasis could exhibit varied capacities in different stages of organismal lifespan. Recently, an efficient metazoan disaggregase activity was identified in vitro, which requires the Hsp70 chaperone and Hsp110 nucleotide exchange factor, together with single or cooperating J‐protein co‐chaperones of classes A and B. Here, we describe how the orthologous Hsp70s and J‐protein of Caenorhabditis elegans work together to resolve protein aggregates both i...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Janine Kirstein, Kristin Arnsburg, Annika Scior, Anna Szlachcic, D. Lys Guilbride, Richard I. Morimoto, Bernd Bukau, Nadinath B. Nillegoda Tags: Original Article Source Type: research

Sirtuins at the crossroads of stemness, aging, and cancer
Summary Sirtuins are stress‐responsive proteins that direct various post‐translational modifications (PTMs) and as a result, are considered to be master regulators of several cellular processes. They are known to both extend lifespan and regulate spontaneous tumor development. As both aging and cancer are associated with altered stem cell function, the possibility that the involvement of sirtuins in these events is mediated by their roles in stem cells is worthy of investigation. Research to date suggests that the individual sirtuin family members can differentially regulate embryonic, hematopoietic as well as other ad...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Carol O'Callaghan, Athanassios Vassilopoulos Tags: Review Source Type: research

Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
Summary Sirtuin 2 (SIRT2) is a member of a family of NAD+‐dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle‐aged, 13‐month‐old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal ...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: St éphane Fourcade, Laia Morató, Janani Parameswaran, Montserrat Ruiz, Tatiana Ruiz‐Cortés, Mariona Jové, Alba Naudí, Paloma Martínez‐Redondo, Mara Dierssen, Isidre Ferrer, Francesc Villarroya, Reinald Pamplona, Alejandro Vaquero, Manel Portero Tags: Original Article Source Type: research

Dopamine D4 receptor activation restores CA1 LTP in hippocampal slices from aged mice
Summary Normal aging is characterized with a decline in hippocampal memory functions that is associated with changes in long‐term potentiation (LTP) of the CA3‐to‐CA1 synapse. Age‐related deficit of the dopaminergic system may contribute to impairment of CA1 LTP. Here we assessed how the modulation of CA1 LTP by dopamine is affected by aging and how it is dependent on the Ca2+ source. In slices from adult mice, the initial slope of the field potential showed strong LTP, but in slices from aged mice LTP was impaired. Dopamine did not affect LTP in adult slices, but enhanced LTP in aged slices. The dopamine D1/D5 rec...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Fangli Guo, Jianhua Zhao, Dandan Zhao, Jiangang Wang, Xiaofang Wang, Zhiwei Feng, Martin Vreugdenhil, Chengbiao Lu Tags: Original Article Source Type: research

TOR ‐mediated regulation of metabolism in aging
Summary Cellular metabolism is regulated by the mTOR kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging. The mTOR pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. The nutrient‐sensing pathway is regulated at the lysosomal membrane by a number of proteins for which deficiency triggers widespread aging phenotypes in tested animal models. In response to environmental cues, this recently discovered lysosomal nutrient‐sensing complex regulates autophagy tran...
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Henri Antikainen, Monica Driscoll, Gal Haspel, Radek Dobrowolski Tags: Review Source Type: research

miR ‐155 induces ROS generation through downregulation of antioxidation‐related genes in mesenchymal stem cells
In conclusion, our study suggests that miR‐155 is an important mediator connecting aging, inflammation, and ROS generation in stem cells. (Source: Aging Cell)
Source: Aging Cell - October 1, 2017 Category: Cytology Authors: Yuta Onodera, Takeshi Teramura, Toshiyuki Takehara, Kayoko Obora, Tatsufumi Mori, Kanji Fukuda Tags: Original Article Source Type: research

MicroRNAs mir ‐184 and let‐7 alter Drosophila metabolism and longevity
Summary MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression associated with many complex biological processes. By comparing miRNA expression between long‐lived cohorts of Drosophila melanogaster that were fed a low‐nutrient diet with normal‐lived control animals fed a high‐nutrient diet, we identified miR‐184, let‐7, miR‐125, and miR‐100 as candidate miRNAs involved in modulating aging. We found that ubiquitous, adult‐specific overexpression of these individual miRNAs led to significant changes in fat metabolism and/or lifespan. Most impressively, adult‐specific overexpression of le...
Source: Aging Cell - September 30, 2017 Category: Cytology Authors: Christi M. Gendron, Scott D. Pletcher Tags: Short Take Source Type: research

Caloric restriction stabilizes body weight and accelerates behavioral recovery in aged rats after focal ischemia
In conclusion, our study shows that recovery from stroke is enhanced in aged rats by a dietary regimen that reduces body weight prior to infarct. (Source: Aging Cell)
Source: Aging Cell - September 29, 2017 Category: Cytology Authors: Ovidiu Ciobanu, Raluca Elena Sandu, Adrian Tudor Balseanu, Alexandra Zavaleanu, Andrei Gresita, Eugen Bogdan Petcu, Adriana Uzoni, Aurel Popa ‐Wagner Tags: Original Article Source Type: research

Sexually divergent DNA methylation patterns with hippocampal aging
Summary DNA methylation is a central regulator of genome function, and altered methylation patterns are indicative of biological aging and mortality. Age‐related cellular, biochemical, and molecular changes in the hippocampus lead to cognitive impairments and greater vulnerability to neurodegenerative disease that varies between the sexes. The role of hippocampal epigenomic changes with aging in these processes is unknown as no genome‐wide analyses of age‐related methylation changes have considered the factor of sex in a controlled animal model. High‐depth, genome‐wide bisulfite sequencing of young (3 month)...
Source: Aging Cell - September 26, 2017 Category: Cytology Authors: Dustin R. Masser, Niran Hadad, Hunter L. Porter, Colleen A. Mangold, Archana Unnikrishnan, Matthew M. Ford, Cory B. Giles, Constantin Georgescu, Mikhail G. Dozmorov, Jonathan D. Wren, Arlan Richardson, David R. Stanford, Willard M. Freeman Tags: Original Article Source Type: research

Gene therapy with the TRF1 telomere gene rescues decreased TRF1 levels with aging and prolongs mouse health span
Summary The shelterin complex protects telomeres by preventing them from being degraded and recognized as double‐strand DNA breaks. TRF1 is an essential component of shelterin, with important roles in telomere protection and telomere replication. We previously showed that TRF1 deficiency in the context of different mouse tissues leads to loss of tissue homeostasis owing to impaired stem cell function. Here, we show that TRF1 levels decrease during organismal aging both in mice and in humans. We further show that increasing TRF1 expression in both adult (1‐year‐old) and old (2‐year‐old) mice using gene therapy can...
Source: Aging Cell - September 25, 2017 Category: Cytology Authors: Aksinya Derevyanko, Kurt Whittemore, Ralph P. Schneider, Ver ónica Jiménez, Fàtima Bosch, Maria A. Blasco Tags: Original Article Source Type: research

Transthyretin deposition promotes progression of osteoarthritis
Summary Deposition of amyloid is a common aging‐associated phenomenon in several aging‐related diseases. Osteoarthritis (OA) is the most prevalent joint disease, and aging is its major risk factor. Transthyretin (TTR) is an amyloidogenic protein that is deposited in aging and OA‐affected human cartilage and promotes inflammatory and catabolic responses in cultured chondrocytes. Here, we investigated the role of TTR in vivo using transgenic mice overexpressing wild‐type human TTR (hTTR‐TG). Although TTR protein was detected in cartilage in hTTR‐TG mice, the TTR transgene was highly overexpressed in liver, b...
Source: Aging Cell - September 23, 2017 Category: Cytology Authors: Tokio Matsuzaki, Yukio Akasaki, Merissa Olmer, Oscar Alvarez ‐Garcia, Natalia Reixach, Joel N. Buxbaum, Martin K. Lotz Tags: Original Article Source Type: research

Genetic interaction with temperature is an important determinant of nematode longevity
Summary As in other poikilotherms, longevity in C. elegans varies inversely with temperature; worms are longer‐lived at lower temperatures. While this observation may seem intuitive based on thermodynamics, the molecular and genetic basis for this phenomenon is not well understood. Several recent reports have argued that lifespan changes across temperatures are genetically controlled by temperature‐specific gene regulation. Here, we provide data that both corroborate those studies and suggest that temperature‐specific longevity is more the rule than the exception. By measuring the lifespans of worms with single ...
Source: Aging Cell - September 22, 2017 Category: Cytology Authors: Hillary Miller, Marissa Fletcher, Melissa Primitivo, Alison Leonard, George L. Sutphin, Nicholas Rintala, Matt Kaeberlein, Scott F. Leiser Tags: Short Take Source Type: research

In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles
Summary Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age‐associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied p...
Source: Aging Cell - September 18, 2017 Category: Cytology Authors: Erez Eitan, Valeria Tosti, Caitlin N. Suire, Edda Cava, Sean Berkowitz, Beatrice Bertozzi, Sophia M. Raefsky, Nicola Veronese, Ryan Spangler, Francesco Spelta, Maja Mustapic, Dimitrios Kapogiannis, Mark P. Mattson, Luigi Fontana Tags: Short Take Source Type: research

Issue Information
(Source: Aging Cell)
Source: Aging Cell - September 12, 2017 Category: Cytology Tags: Issue Information Source Type: research

Hyperphosphatemia induces senescence in human endothelial cells by increasing endothelin ‐1 production
Summary Hyperphosphatemia is related to some pathologies, affecting vascular cell behavior. This work analyzes whether high concentration of extracellular phosphate induces endothelial senescence through up‐regulation of endothelin‐1 (ET‐1), exploring the mechanisms involved. The phosphate donor β‐glycerophosphate (BGP) in human endothelial cells increased ET‐1 production, endothelin‐converting enzyme‐1 (ECE‐1) protein, and mRNA expression, which depend on the AP‐1 activation through ROS production. In parallel, BGP also induced endothelial senescence by increasing p16 expression and the senescence...
Source: Aging Cell - August 31, 2017 Category: Cytology Authors: Gemma Olmos, Patricia Mart ínez‐Miguel, Elena Alcalde‐Estevez, Diana Medrano, Patricia Sosa, Leocadio Rodríguez‐Mañas, Manuel Naves‐Diaz, Diego Rodríguez‐Puyol, María Piedad Ruiz‐Torres, Susana López‐Ongil Tags: Original Article Source Type: research

Opposing effects on cardiac function by calorie restriction in different ‐aged mice
Summary Calorie restriction (CR) increases average and maximum lifespan and exhibits an apparent beneficial impact on age‐related diseases. Several studies have shown that CR initiated either in middle or old age could improve ischemic tolerance and rejuvenate the aging heart; however, the data are not uniform when initiated in young. The accurate time to initiate CR providing maximum benefits for cardiac remodeling and function during aging remains unclear. Thus, whether a similar degree of CR initiated in mice of different ages could exert a similar effect on myocardial protection was investigated in this study. C57BL/...
Source: Aging Cell - August 11, 2017 Category: Cytology Authors: Yunlu Sheng, Shan Lv, Min Huang, Yifan Lv, Jing Yu, Juan Liu, Tingting Tang, Hanmei Qi, Wenjuan Di, Guoxian Ding Tags: Original Article Source Type: research

In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging
Summary Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons. However, lack of Pink1 or Parkin did not lead to the accumulation of axonal mitochond...
Source: Aging Cell - August 7, 2017 Category: Cytology Authors: Xu Cao, Haiqiong Wang, Zhao Wang, Qingyao Wang, Shuang Zhang, Yuanping Deng, Yanshan Fang Tags: Original Article Source Type: research

The ω‐3 fatty acid α‐linolenic acid extends Caenorhabditis elegans lifespan via NHR‐49/PPARα and oxidation to oxylipins
Summary The dietary intake of ω‐3 polyunsaturated fatty acids has been linked to a reduction in the incidence of aging‐associated disease including cardiovascular disease and stroke. Additionally, long‐lived Caenorhabditis elegans glp‐1 germ line‐less mutant animals show a number of changes in lipid metabolism including the increased production of the ω‐3 fatty acid, α‐linolenic acid (ALA). Here, we show that the treatment of C. elegans with ALA produces a dose‐dependent increase in lifespan. The increased longevity of the glp‐1 mutant animals is known to be dependent on both the NH...
Source: Aging Cell - August 3, 2017 Category: Cytology Authors: Wenbo Qi, Gloria E. Gutierrez, Xiaoli Gao, Hong Dixon, Joe A. McDonough, Ann M. Marini, Alfred L. Fisher Tags: Original Article Source Type: research

Deficiency of CCAAT/enhancer ‐binding protein homologous protein (CHOP) prevents diet‐induced aortic valve calcification in vivo
Summary Aortic valve (AoV) calcification is common in aged populations. Its subsequent aortic stenosis has been linked with increased morbidity, but still has no effective pharmacological intervention. Our previous data show endoplasmic reticulum (ER) stress is involved in AoV calcification. Here, we investigated whether deficiency of ER stress downstream effector CCAAT/enhancer‐binding protein homology protein (CHOP) may prevent development of AoV calcification. AoV calcification was evaluated in Apoe−/− mice (n = 10) or in mice with dual deficiencies of ApoE and CHOP (Apoe−/−CHOP&minus...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Zhejun Cai, Baoqing Liu, Jia Wei, Zurong Fu, Yidong Wang, Yaping Wang, Jian Shen, Liangliang Jia, Shengan Su, Xiaoya Wang, Xiaoping Lin, Han Chen, Fei Li, Jian'an Wang, Meixiang Xiang Tags: Original Article Source Type: research

Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy
Summary Female middle age is characterized by a decline in skeletal muscle mass and performance, predisposing women to sarcopenia, functional limitations, and metabolic dysfunction as they age. Menopausal loss of ovarian function leading to low circulating level of 17β‐estradiol has been suggested as a contributing factor to aging‐related muscle deterioration. However, the underlying molecular mechanisms remain largely unknown and thus far androgens have been considered as a major anabolic hormone for skeletal muscle. We utilized muscle samples from 24 pre‐ and postmenopausal women to establish proteome‐wide p...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Eija K. Laakkonen, Rabah Soliymani, Sira Karvinen, Jaakko Kaprio, Urho M. Kujala, Marc Baumann, Sarianna Sipil ä, Vuokko Kovanen, Maciej Lalowski Tags: Original Article Source Type: research

The acceleration of reproductive aging in Nrg1flox/flox;Cyp19 ‐Cre female mice
In this study, because the granulosa cell‐specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotypes similar to older women, we sought to understand the mechanisms of ovarian aging and to develop a new strategy for improving fertility in older women prior to menopause. In the ovary of 6‐month‐old gcNrg1KO mice, follicular development was blocked in bilayer secondary follicles and heterogeneous cells accumulated in ovarian stroma. The heterogeneous cells in ovarian stroma were distinguished as two different types: (i) the LH receptor‐positive endocrine cells and (ii) actin‐rich fibrotic cell...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Takashi Umehara, Tomoko Kawai, Ikko Kawashima, Katsuhiro Tanaka, Satoshi Okuda, Hiroya Kitasaka, JoAnne S. Richards, Masayuki Shimada Tags: Original Article Source Type: research

Can FSH influence longevity?
Summary It was recently reported that the extragonadal actions of follicle‐stimulating hormone (FSH) include regulation of brown and white adipose tissue function and thermogenesis. Based on these findings and on our evidence for reduced FSH levels and enhanced thermogenesis in long‐lived growth hormone (GH)‐deficient mice and GH‐resistant mice, we suggest that FSH may have a role in the control of aging and longevity. We speculate that alterations in FSH secretion may represent one of the mechanisms of trade‐offs between reproduction and aging. (Source: Aging Cell)
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Andrzej Bartke Tags: Commentary Source Type: research

Wide ‐scale comparative analysis of longevity genes and interventions
Summary Hundreds of genes, when manipulated, affect the lifespan of model organisms (yeast, worm, fruit fly, and mouse) and thus can be defined as longevity‐associated genes (LAGs). A major challenge is to determine whether these LAGs are model‐specific or may play a universal role as longevity regulators across diverse taxa. A wide‐scale comparative analysis of the 1805 known LAGs across 205 species revealed that (i) LAG orthologs are substantially overrepresented, from bacteria to mammals, compared to the entire genomes or interactomes, and this was especially noted for essential LAGs; (ii) the effects on lifespan,...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Hagai Yanai, Arie Budovsky, Thomer Barzilay, Robi Tacutu, Vadim E. Fraifeld Tags: Original Article Source Type: research

Sex differences in lifespan extension with acarbose and 17 ‐α estradiol: gonadal hormones underlie male‐specific improvements in glucose tolerance and mTORC2 signaling
Summary Interventions that extend lifespan in mice can show substantial sexual dimorphism. Here, we show that male‐specific lifespan extension with two pharmacological treatments, acarbose (ACA) and 17‐α estradiol (17aE2), is associated, in males only, with increased insulin sensitivity and improved glucose tolerance. Females, which show either smaller (ACA) or no lifespan extension (17aE2), do not derive these metabolic benefits from drug treatment. We find that these male‐specific metabolic improvements are associated with enhanced hepatic mTORC2 signaling, increased Akt activity, and phosphorylation of FOXO1...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Michael Garratt, Brian Bower, Gonzalo G. Garcia, Richard A. Miller Tags: Original Article Source Type: research

In aged primary T cells, mitochondrial stress contributes to telomere attrition measured by a novel imaging flow cytometry assay
Summary The decline of the immune system with age known as immune senescence contributes to inefficient pathogen clearance and is a key risk factor for many aged‐related diseases. However, reversing or halting immune aging requires more knowledge about the cell biology of senescence in immune cells. Telomere shortening, low autophagy and mitochondrial dysfunction have been shown to underpin cell senescence. While autophagy has been found to control mitochondrial damage, no link has been made to telomere attrition. In contrast, mitochondrial stress can contribute to telomere attrition and vice versa. Whereas this link has...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Sharon Lesley Sanderson, Anna Katharina Simon Tags: Original Article Source Type: research

A multimethod computational simulation approach for investigating mitochondrial dynamics and dysfunction in degenerative aging
Summary Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by inclu...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Timothy E. Hoffman, Katherine J. Barnett, Lyle Wallis, William H. Hanneman Tags: Original Article Source Type: research

The valosin ‐containing protein is a novel repressor of cardiomyocyte hypertrophy induced by pressure overload
In conclusion, VCP acts as a novel repressor that is able to prevent cardiomyocyte hypertrophy from pressure overload by modulating the mTORC1 signaling pathway. (Source: Aging Cell)
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Ning Zhou, Ben Ma, Shaunrick Stoll, Tristan T. Hays, Hongyu Qiu Tags: Original Article Source Type: research

Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
Summary Hypertension is a well‐established risk factor for adverse cardiovascular events, and older age is a risk factor for the development of hypertension. Genomewide association studies have linked ATP2B1, the gene for the plasma membrane calcium ATPase 1 (PMCA1), to blood pressure (BP) and hypertension. Here, we present the effects of reduction in the expression of PMCA1 on BP and small artery structure and function when combined with advancing age. Heterozygous PMCA1 null mice (PMCA1Ht) were generated and conscious BP was measured at 6 to 18 months of age. Passive and active properties of isolated small mesente...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Robert Little, Min Zi, Sally K. Hammad, Loan Nguyen, Alexandra Njegic, Sathishkumar Kurusamy, Sukhpal Prehar, Angel L. Armesilla, Ludwig Neyses, Clare Austin, Elizabeth J. Cartwright Tags: Original Article Source Type: research

Autophagy in stem cell aging
Summary Aging is responsible for changes in mammalian tissues that result in an imbalance to tissue homeostasis and a decline in the regeneration capacity of organs due to stem cell exhaustion. Autophagy is a constitutive pathway necessary to degrade damaged organelles and protein aggregates. Autophagy is one of the hallmarks of aging, which involves a decline in the number and functionality of stem cells. Recent studies show that stem cells require autophagy to get rid of cellular waste produced during the quiescent stage. In particular, two independent studies in muscle and hematopoietic stem cells demonstrate the releva...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Miren Revuelta, Ander Matheu Tags: Commentary Source Type: research

Dyrk1 inhibition improves Alzheimer's disease ‐like pathology
Summary There is an urgent need for the development of new therapeutic strategies for Alzheimer's disease (AD). The dual‐specificity tyrosine phosphorylation‐regulated kinase‐1A (Dyrk1a) is a protein kinase that phosphorylates the amyloid precursor protein (APP) and tau and thus represents a link between two key proteins involved in AD pathogenesis. Furthermore, Dyrk1a is upregulated in postmortem human brains, and high levels of Dyrk1a are associated with mental retardation. Here, we sought to determine the effects of Dyrk1 inhibition on AD‐like pathology developed by 3xTg‐AD mice, a widely used animal model of ...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Caterina Branca, Darren M. Shaw, Ramona Belfiore, Vijay Gokhale, Arthur Y. Shaw, Christopher Foley, Breland Smith, Christopher Hulme, Travis Dunckley, Bessie Meechoovet, Antonella Caccamo, Salvatore Oddo Tags: Original Article Source Type: research

HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease
In conclusion, our results indicate that HDAC3 negatively regulates spatial memory in APP/PS1 mice and HDAC3 inhibition might represent a potential therapy for the treatment of AD. (Source: Aging Cell)
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Xiaolei Zhu, Sulei Wang, Linjie Yu, Jiali Jin, Xing Ye, Yi Liu, Yun Xu Tags: Original Article Source Type: research

Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers
Summary Reduced neurogenesis in the aging mammalian hippocampus has been linked to cognitive deficits and increased risk of dementia. We utilized postmortem human hippocampal tissue from 26 subjects aged 18–88 years to investigate changes in expression of six genes representing different stages of neurogenesis across the healthy adult lifespan. Progressive and significant decreases in mRNA levels of the proliferation marker Ki67 (MKI67) and the immature neuronal marker doublecortin (DCX) were found in the healthy human hippocampus over the lifespan. In contrast, expression of genes for the stem cell marker glial...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Kathryn J. Mathews, Katherine M. Allen, Danny Boerrigter, Helen Ball, Cynthia Shannon Weickert, Kay L. Double Tags: Short Take Source Type: research