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https://www.readbyqxmd.com/read/27913291/a-saposin-deficiency-model-in-drosophila-lysosomal-storage-progressive-neurodegeneration-and-sensory-physiological-decline
#1
Samantha J Hindle, Sarita Hebbar, Dominik Schwudke, Christopher J Elliott, Sean T Sweeney
Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids...
November 29, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27905558/microrna-mir-34-provides-robustness-to-environmental-stress-response-via-the-daf-16-network-in-c-elegans
#2
Meltem Isik, T Keith Blackwell, Eugene Berezikov
Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following stress in human cells. However, the biological significance of this response was unclear. Here we show that in C. elegans mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damage...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899767/immune-function-parameters-as-markers-of-biological-age-and-predictors-of-longevity
#3
Irene Martínez de Toda, Ianire Maté, Carmen Vida, Julia Cruces, Mónica De la Fuente
Chronological age is not a good indicator of how each individual ages and thus how to maintain good health. Due to the long lifespan in humans and the consequent difficulty of carrying out longitudinal studies, finding valid biomarkers of the biological age has been a challenge both for research and clinical studies. The aim was to identify and validate several immune cell function parameters as markers of biological age. Adult, mature, elderly and long-lived human volunteers were used. The chemotaxis, phagocytosis, natural killer activity and lymphoproliferation in neutrophils and lymphocytes of peripheral blood were analyzed...
November 28, 2016: Aging
https://www.readbyqxmd.com/read/27898463/transplantation-tolerance-after-allograft-rejection
#4
Michelle L Miller, Maria-Luisa Alegre, Anita S Chong
PURPOSE OF REVIEW: Although elusive for many decades, transplantation tolerance can now be achieved in the clinic. This has prompted follow-up investigations into its stability and longevity, as well as into barriers to its induction, which include memory T and B cells. RECENT FINDINGS: Clinical observations reveal that transplantation tolerance can be induced in adult recipients and that even episodes of acute rejection do not preclude successful weaning from immunosuppression to reveal tolerance...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27892468/somatic-increase-of-cct8-mimics-proteostasis-of-human-pluripotent-stem-cells-and-extends-c-elegans-lifespan
#5
Alireza Noormohammadi, Amirabbas Khodakarami, Ricardo Gutierrez-Garcia, Hyun Ju Lee, Seda Koyuncu, Tim König, Christina Schindler, Isabel Saez, Azra Fatima, Christoph Dieterich, David Vilchez
Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27884780/regulation-of-metabolic-health-and-aging-by-nutrient-sensitive-signaling-pathways
#6
Nicole E Cummings, Dudley W Lamming
All organisms need to be capable of adapting to changes in the availability and composition of nutrients. Over 75 years ago, researchers discovered that a calorie restricted (CR) diet could significantly extend the lifespan of rats, and since then a CR diet has been shown to increase lifespan and healthspan in model organisms ranging from yeast to non-human primates. In this review, we discuss the effects of a CR diet on metabolism and healthspan, and highlight emerging evidence that suggests that dietary composition - the precise macronutrients that compose the diet - may be just as important as caloric content...
November 21, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27876455/multiple-morbidities-in-companion-dogs-a-novel-model-for-investigating-age-related-disease
#7
Kelly Jin, Jessica M Hoffman, Kate E Creevy, Dan G O'Neill, Daniel E L Promislow
The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons...
2016: Pathobiology of Aging & Age related Diseases
https://www.readbyqxmd.com/read/27872299/the-emergence-of-longevous-populations
#8
Fernando Colchero, Roland Rau, Owen R Jones, Julia A Barthold, Dalia A Conde, Adam Lenart, Laszlo Nemeth, Alexander Scheuerlein, Jonas Schoeley, Catalina Torres, Virginia Zarulli, Jeanne Altmann, Diane K Brockman, Anne M Bronikowski, Linda M Fedigan, Anne E Pusey, Tara S Stoinski, Karen B Strier, Annette Baudisch, Susan C Alberts, James W Vaupel
The human lifespan has traversed a long evolutionary and historical path, from short-lived primate ancestors to contemporary Japan, Sweden, and other longevity frontrunners. Analyzing this trajectory is crucial for understanding biological and sociocultural processes that determine the span of life. Here we reveal a fundamental regularity. Two straight lines describe the joint rise of life expectancy and lifespan equality: one for primates and the second one over the full range of human experience from average lifespans as low as 2 y during mortality crises to more than 87 y for Japanese women today...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27846777/development-and-characterization-of-in-vitro-human-oral-mucosal-equivalents-derived-from-immortalized-oral-keratinocytes
#9
Luke R Jennings, Helen E Colley, Jane Ong, Foti Panagakos, James G Masters, Harsh M Trivedi, Craig Murdoch, Simon Whawell
Tissue-engineered oral mucosal equivalents (OME) are being increasingly used to measure toxicity, drug delivery, and to model oral diseases. Current OME mainly comprise normal oral keratinocytes (NOK) cultured on top of a normal oral fibroblasts-containing matrix. However, the commercial supply of NOK is limited, restricting widespread use of these mucosal models. In addition, NOK suffer from poor longevity and donor-to-donor variability. Therefore, we constructed, characterized, and tested the functionality of OME based on commercial TERT2-immortalized oral keratinocytes (FNB6) to produce a more readily available alternative to NOK-based OME...
December 2, 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27843312/formulation-characterization-and-tissue-distribution-of-a-novel-ph-sensitive-long-circulating-liposome-based-theranostic-suitable-for-molecular-imaging-and-drug-delivery
#10
Yin Duan, Lihui Wei, Julia Petryk, Terrence D Ruddy
PURPOSE: When designing liposome formulas for treatment and diagnostic purposes, two of the most common challenges are 1) the lack of a specific release mechanism for the encapsulated contents and 2) a short circulation time due to poor resistance to biological fluids. This study aimed to create a liposome formula with prolonged in vivo longevity and pH-sensitivity for cytoplasmic drug delivery. MATERIALS AND METHODS: Liposomal particles were generated using hydrogenated soy (HS) phosphatidylcholine, cholesteryl hemisuccinate (CHEM), polyethylene glycol (PEG) and diethylenetriaminepentaacetic acid-modified phosphatidylethanolamine with film hydration and extrusion methods...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27837429/quantifying-intrinsic-and-extrinsic-contributions-to-human-longevity-application-of-a-two-process-vitality-model-to-the-human-mortality-database
#11
David J Sharrow, James J Anderson
The rise in human life expectancy has involved declines in intrinsic and extrinsic mortality processes associated, respectively, with senescence and environmental challenges. To better understand the factors driving this rise, we apply a two-process vitality model to data from the Human Mortality Database. Model parameters yield intrinsic and extrinsic cumulative survival curves from which we derive intrinsic and extrinsic expected life spans (ELS). Intrinsic ELS, a measure of longevity acted on by intrinsic, physiological factors, changed slowly over two centuries and then entered a second phase of increasing longevity ostensibly brought on by improvements in old-age death reduction technologies and cumulative health behaviors throughout life...
December 2016: Demography
https://www.readbyqxmd.com/read/27832764/blood-mirnomes-and-transcriptomes-reveal-novel-longevity-mechanisms-in-the-long-lived-bat-myotis-myotis
#12
Zixia Huang, David Jebb, Emma C Teeling
BACKGROUND: Chiroptera, the bats, are the only order of mammals capable of true self-powered flight. Bats exhibit a number of other exceptional traits such as echolocation, viral tolerance and, perhaps most puzzlingly, extreme longevity given their body size. Little is known about the molecular mechanisms driving their extended longevity particularly at the levels of gene expression and post-transcriptional regulation. To elucidate the molecular mechanisms that may underlie their unusual longevity, we have deep sequenced 246...
November 10, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27824314/a-serum-mirna-profile-of-human-longevity-findings-from-the-baltimore-longitudinal-study-of-aging-blsa
#13
Thalyana Smith-Vikos, Zuyun Liu, Christine Parsons, Myriam Gorospe, Luigi Ferrucci, Thomas M Gill, Frank J Slack
In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92...
November 7, 2016: Aging
https://www.readbyqxmd.com/read/27818232/the-genetics-of-exceptional-longevity-identifies-new-druggable-targets-for-vascular-protection-and-repair
#14
REVIEW
Annibale A Puca, Gaia Spinetti, Rosa Vono, Carmine Vecchione, Paolo Madeddu
Therapeutic angiogenesis is a relatively new medical strategy in the field of cardiovascular diseases. The underpinning concept is that angiogenic growth factors or proangiogenic cells could be exploited therapeutically in cardiovascular patients to enhance native revascularization responses to an ischemic insult, thereby accelerating tissue healing. The initial enthusiasm generated by preclinical studies has been tempered by the modest success of clinical trials assessing therapeutic angiogenesis. Similarly, proangiogenic cell therapy has so far not maintained the original promises...
November 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27810910/the-lysosomal-membrane-protein-scav-3-maintains-lysosome-integrity-and-adult-longevity
#15
Yuan Li, Baohui Chen, Wei Zou, Xin Wang, Yanwei Wu, Dongfeng Zhao, Yanan Sun, Yubing Liu, Lianwan Chen, Long Miao, Chonglin Yang, Xiaochen Wang
Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics...
October 24, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27806476/older-adults-perception-of-their-needs-in-tehran-a-cry-for-emotional-and-social-support
#16
Sima Ghasemi, Nastaran Keshavarz Mohammadi, Farahnaz Mohammadi Shahboulaghi, Ali Ramezankhani
INTRODUCTION: Background and purpose: Human's longevity has increased with advances in health and better management of communicable diseases. Therefore, the number of older adult is increasing in developed and developing countries. A glimpse at studies reveals that identifying elderly's health needs has been mainly based on the experts' understanding, while older adult themselves have rarely expressed their own opinions. This study aimed to better understand Tehran, Iran elderly's perception of their own health needs...
June 30, 2016: Global Journal of Health Science
https://www.readbyqxmd.com/read/27799874/enhanced-viral-replication-by-cellular-replicative-senescence
#17
Ji-Ae Kim, Rak-Kyun Seong, Ok Sarah Shin
Cellular replicative senescence is a major contributing factor to aging and to the development and progression of aging-associated diseases. In this study, we sought to determine viral replication efficiency of influenza virus (IFV) and Varicella Zoster Virus (VZV) infection in senescent cells. Primary human bronchial epithelial cells (HBE) or human dermal fibroblasts (HDF) were allowed to undergo numbers of passages to induce replicative senescence. Induction of replicative senescence in cells was validated by positive senescence-associated β-galactosidase staining...
October 2016: Immune Network
https://www.readbyqxmd.com/read/27799553/online-social-integration-is-associated-with-reduced-mortality-risk
#18
William R Hobbs, Moira Burke, Nicholas A Christakis, James H Fowler
Social interactions increasingly take place online. Friendships and other offline social ties have been repeatedly associated with human longevity, but online interactions might have different properties. Here, we reference 12 million social media profiles against California Department of Public Health vital records and use longitudinal statistical models to assess whether social media use is associated with longer life. The results show that receiving requests to connect as friends online is associated with reduced mortality but initiating friendships is not...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27799538/genetic-variants-linked-to-education-predict-longevity
#19
Riccardo E Marioni, Stuart J Ritchie, Peter K Joshi, Saskia P Hagenaars, Aysu Okbay, Krista Fischer, Mark J Adams, W David Hill, Gail Davies, Reka Nagy, Carmen Amador, Kristi Läll, Andres Metspalu, David C Liewald, Archie Campbell, James F Wilson, Caroline Hayward, Tõnu Esko, David J Porteous, Catharine R Gale, Ian J Deary
Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27794564/human-exceptional-longevity-transcriptome-from-centenarians-is-distinct-from-septuagenarians-and-reveals-a-role-of-bcl-xl-in-successful-aging
#20
Consuelo Borras, Kheira M Abdelaziz, Juan Gambini, Eva Serna, Marta Inglés, Monica de la Fuente, Idoia Garcia, Ander Matheu, Paula Sanchís, Angel Belenguer, Alessandra Errigo, Juan-Antonio Avellana, Ana Barettino, Carla Lloret-Fernández, Nuria Flames, Gianni Pes, Leocadio Rodriguez-Mañas, Jose Viña
Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl - xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging...
October 28, 2016: Aging
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