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    NKILA inhibits NF-κB signaling and suppresses tumor metastasis.
    Aging (Albany NY) 2018 Jan 17. Epub 2018 Jan 17.
    Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
    The long non-coding RNA (lncRNA) NKILA (nuclear transcription factor NF-κB interacting lncRNA) functions as a suppressor in human breast cancer and tongue cancer. However, the clinical significance and biological roles of NKILA in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we showed that NKILA was downregulated in ESCC tissues and cancer cells compared with their normal counterparts. Read More

    HOXC6 predicts invasion and poor survival in hepatocellular carcinoma by driving epithelial-mesenchymal transition.
    Aging (Albany NY) 2018 Jan 15. Epub 2018 Jan 15.
    Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
    Aberrant expression of HOXC6 has been reported in several malignant tumors, yet little is known about the value of HOXC6 in invasion and prognosis of hepatocellular carcinoma (HCC). HOXC6 expression was positively correlated with high AFP level, liver cirrhosis, larger tumor, vascular invasion and BCLC stage. Kaplan-Meier analysis revealed that HOXC6 was an independent predictor for overall survival (OS) and time to recurrence (TTR). Read More

    Rapamycin prevents the intervertebral disc degeneration via inhibiting differentiation and senescence of annulus fibrosus cells.
    Aging (Albany NY) 2018 Jan 18. Epub 2018 Jan 18.
    Department of Orthopedic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P. R. China.
    The effects of bleomycin and rapamycin on cellular senescence and differentiation of rabbit annulus fibrosus stem cells (AFSCs) were investigated using a cell culture model. The results showed that bleomycin induced cellular senescence in AFSCs as evidenced by senescence-associated secretory phenotype. The morphology of AFSCs was changed from cobblestone-like cells to pancake-like cells. Read More

    Effects of senescence and angiotensin II on expression and processing of amyloid precursor protein in human cerebral microvascular endothelial cells.
    Aging (Albany NY) 2018 Jan 15. Epub 2018 Jan 15.
    Department of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
    The present study was designed to determine the effects of senescence and angiotensin II (Ang II) on expression and processing of amyloid precursor protein (APP) in human brain microvascular endothelial cells (BMECs). Senescence caused a decrease in APP expression thereby resulting in reduced secretion of soluble APPα (sAPPα). In contrast, β-site APP cleaving enzyme (BACE1) expression and production of amyloid β (Aβ)40 were increased in senescent endothelium. Read More

    Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.
    Aging (Albany NY) 2018 Jan 11. Epub 2018 Jan 11.
    Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
    Background: Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. Read More

    Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.
    Aging (Albany NY) 2018 01 8. Epub 2018 Jan 8.
    Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
    Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28-days repeated-dose tolerance study. Read More

    Associations between the components of metabolic syndrome and the polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-γ), the fat mass and obesity-associated (FTO), and the melanocortin-4 receptor (MC4R) genes.
    Aging (Albany NY) 2018 Jan 9. Epub 2018 Jan 9.
    Department of Nursing, Pomeranian Medical University in Szczecin, Szczecin, 71-210, Poland.
    Introduction: Metabolic syndrome (MetS) is regarded as a set of abnormalities, increasing the risk of serious functioning disorders. It can develop as a result of genetic predisposition.

    Aim: The aim of this study was to establish associations between MetS-related abnormalities and the PPAR-γ rs1801282, FTO rs9939609, and MC4R rs17782313 polymorphisms. Read More

    Muscle function decline and mitochondria changes in middle age precede sarcopenia in mice.
    Aging (Albany NY) 2018 Jan 4. Epub 2018 Jan 4.
    Center for Exercise, Metabolism and Cancer, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
    Sarcopenia is the degenerative loss of muscle mass and strength with aging. Although a role of mitochondrial metabolism in muscle function and in the development of many diseases has been described, the role of mitochondrial topology and dynamics in the process of muscle aging is not fully understood. This work shows a time line of changes in both mitochondrial distribution and skeletal muscle function during mice lifespan. Read More

    Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression.
    Aging (Albany NY) 2017 Dec;9(12):2666-2694
    Cancer Sciences, University of Southampton, Somers Building, Southampton General Hospital, Southampton SO16 6YD, UK.
    Colorectal cancer is a global disease with increasing incidence. Mortality is largely attributed to metastatic spread and therefore, a mechanistic dissection of the signals which influence tumor progression is needed. Cancer stroma plays a critical role in tumor proliferation, invasion and chemoresistance. Read More

    Clock mediates liver senescence by controlling ER stress.
    Aging (Albany NY) 2017 Dec;9(12):2647-2665
    Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
    Accumulated evidence indicates that circadian genes regulate cell damage and senescence in most mammals. Endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) regulate longevity in many organisms. However, the specific mechanisms of the relationship between the circadian clock and the two stress processes in organisms are poorly understood. Read More

    Transfer of autologous mitochondria from adipose tissue-derived stem cells rescues oocyte quality and infertility in aged mice.
    Aging (Albany NY) 2017 Dec;9(12):2480-2488
    Department of Obstetrics and Gynecology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
    Elder women suffer from low or loss of fertility because of decreasing oocyte quality as maternal aging. As energy resource, mitochondria play pivotal roles in oocyte development, determining oocyte quality. With advanced maternal age, increased dysfunctions emerge in oocyte mitochondria, which decrease oocyte quality and its developmental potential. Read More

    A hypothesis-driven approach identifies CDK4 and CDK6 inhibitors as candidate drugs for treatments of adrenocortical carcinomas.
    Aging (Albany NY) 2017 Dec;9(12):2695-2716
    Pathologies de la Réplication de l'ADN, Université Paris-Diderot - Paris 7, Sorbonne Paris Cité, CNRS UMR7592, Institut Jacques-Monod, 75205 Paris Cedex 13, France.
    High proliferation rate and high mutation density are both indicators of poor prognosis in adrenocortical carcinomas. We performed a hypothesis-driven association study between clinical features in adrenocortical carcinomas and the expression levels of 136 genes involved in DNA metabolism and G1/S phase transition. In 79 samples downloaded from The Cancer Genome Atlas portal, high Cyclin Dependent Kinase 6 (CDK6) mRNA levels gave the most significant association with shorter time to relapse and poorer survival of patients. Read More

    Mitogen-activated protein kinases, Fus3 and Kss1, regulate chronological lifespan in yeast.
    Aging (Albany NY) 2017 Dec;9(12):2587-2609
    Georgia Institute of Technology, School of Biological Sciences, Atlanta, GA 30332, USA.
    Using a systems-based approach, we have identified several genes not previously evaluated for a role(s) in chronological aging. Here, we have thoroughly investigated the chronological lifespan (CLS) of three of these genes (FUS3, KSS1 and HOG1) and their protein products, each of which have well-defined cell signaling roles in young cells. The importance of FUS3 and KSS1 in CLS are largely unknown and analyzed here for the first time. Read More

    Frailty index as a predictor of all-cause and cause-specific mortality in a Swedish population-based cohort.
    Aging (Albany NY) 2017 Dec;9(12):2629-2646
    The Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Frailty is a complex manifestation of aging and associated with increased risk of mortality and poor health outcomes. However, younger individuals (under 65 years) are less-studied in this respect. Also, the relationship between frailty and cause-specific mortality in community settings is understudied. Read More

    MicroRNA-939 inhibits cell proliferation via targeting LRSAM1 in Hirschsprung's disease.
    Aging (Albany NY) 2017 Dec;9(12):2471-2479
    State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
    BackgroundHirschsprung's disease (HSCR) is a common digestive disease caused by impaired development of neural crest cells. Some studies have revealed the roles of microRNA (miRNA) in various diseases. But the function of miRNA in HSCR needs further investigation. Read More

    Targeting flavin-containing enzymes eliminates cancer stem cells (CSCs), by inhibiting mitochondrial respiration: Vitamin B2 (Riboflavin) in cancer therapy.
    Aging (Albany NY) 2017 Dec;9(12):2610-2628
    Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester, UK.
    Here, we performed high-throughput drug-screening to identify new non-toxic mitochondrial inhibitors. This screening platform was specifically designed to detect compounds that selectively deplete cellular ATP levels, but have little or no toxic side effects on cell viability. Using this approach, we identified DPI (Diphenyleneiodonium chloride) as a new potential therapeutic agent. Read More

    Central role of the p53 pathway in the noncoding-RNA response to oxidative stress.
    Aging (Albany NY) 2017 Dec;9(12):2559-2586
    Molecular Cardiology Laboratory, IRCCS Policlinico S. Donato, 20097, San Donato Milanese, Milan, Italy.
    Oxidative stress plays a fundamental role in many conditions. Specifically, redox imbalance inhibits endothelial cell (EC) growth, inducing cell death and senescence. We used global transcriptome profiling to investigate the involvement of noncoding-RNAs in these phenotypes. Read More

    POT1 inhibits the efficiency but promotes the fidelity of nonhomologous end joining at non-telomeric DNA regions.
    Aging (Albany NY) 2017 Dec;9(12):2529-2543
    Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
    Robust DNA double strand break (DSB) repair and stabilized telomeres help maintain genome integrity, preventing the onset of aging or tumorigenesis. POT1 is one of the six factors in the shelterin complex, which protects telomeres from being recognized as DNA damages. TRF1 and TRF2, two other shelterin proteins, have been shown to participate in DNA DSB repair at non-telomeric regions, but whether POT1, which binds to single strand telomeric DNA at chromosomal ends, is involved in DNA DSB repair has not been assessed. Read More

    Human longevity: 25 genetic loci associated in 389,166 UK biobank participants.
    Aging (Albany NY) 2017 Dec;9(12):2504-2520
    Epidemiology and Public Health Group, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Exeter, EX2 5DW, UK.
    We undertook a genome-wide association study (GWAS) of parental longevity in European descent UK Biobank participants. For combined mothers' and fathers' attained age, 10 loci were associated (p<5*10-8), including 8 previously identified for traits including survival, Alzheimer's and cardiovascular disease. Of these, 4 were also associated with longest 10% survival (mothers age ≥90 years, fathers ≥87 years), with 2 additional associations including MC2R intronic variants (coding for the adrenocorticotropic hormone receptor). Read More

    The development of a specific pathogen free (SPF) barrier colony of marmosets (Callithrix jacchus) for aging research.
    Aging (Albany NY) 2017 Dec;9(12):2544-2558
    Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, TX 78245, USA.
    A specific pathogen free (SPF) barrier colony of breeding marmosets (Callithrix jacchus) was established at the Barshop Institute for Longevity and Aging Studies. Rodent and other animal models maintained as SPF barrier colonies have demonstrated improved health and lengthened lifespans enhancing the quality and repeatability of aging research. The marmosets were screened for two viruses and several bacterial pathogens prior to establishing the new SPF colony. Read More

    Sexually dimorphic effects of dietary sugar on lifespan, feeding and starvation resistance in Drosophila.
    Aging (Albany NY) 2017 Dec;9(12):2521-2528
    Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London, WC1E 6BT, UK.
    Lifespan and health in older age are strongly influenced by diet. Feeding Drosophila melanogaster diets high in sugar has increasingly been used as an experimental model to understand the physiological effects of unhealthy, contemporary human diets. Several metabolic parameters and physiological responses to nutrition are known to be dependent on the sex of the animal. Read More

    Age-related gene expression changes, and transcriptome wide association study of physical and cognitive aging traits, in the Lothian Birth Cohort 1936.
    Aging (Albany NY) 2017 Dec;9(12):2489-2503
    Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
    Gene expression is influenced by both genetic variants and the environment. As individuals age, changes in gene expression may be associated with decline in physical and cognitive abilities. We measured transcriptome-wide expression levels in lymphoblastoid cell lines derived from members of the Lothian Birth Cohort 1936 at mean ages 70 and 76 years. Read More

    Selenium preserves keratinocyte stemness and delays senescence by maintaining epidermal adhesion.
    Aging (Albany NY) 2017 Nov;9(11):2302-2315
    Grenoble Alpes University, Grenoble, France.
    Skin is constantly exposed to environmental factors such as pollutants, chemicals and ultra violet radiation (UV), which can induce premature skin aging and increase the risk of skin cancer. One strategy to reduce the effect of oxidative stress produced by environmental exposure is the application of antioxidant molecules. Among the endogenous antioxidants, selenoproteins play a key role in antioxidant defense and in maintaining a reduced cellular environment. Read More

    TNFα-senescence initiates a STAT-dependent positive feedback loop, leading to a sustained interferon signature, DNA damage, and cytokine secretion.
    Aging (Albany NY) 2017 Nov;9(11):2411-2435
    Aging Basic Research Group, Molecular Biology and Biochemistry Research Center for Nanomedicine, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Barcelona, Spain.
    Cellular senescence is a cell fate program that entails essentially irreversible proliferative arrest in response to damage signals. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some types of senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways linking TNFα-related inflammation to senescence are not fully characterized. Read More

    Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells.
    Aging (Albany NY) 2017 Nov;9(11):2397-2410
    State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow 123098, Russia.
    Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γН2АХ foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. Read More

    An expression screen for aged-dependent microRNAs identifies miR-30a as a key regulator of aging features in human epidermis.
    Aging (Albany NY) 2017 Nov;9(11):2376-2396
    Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, University Claude Bernard Lyon I, F69367 Lyon, France.
    The mechanisms affecting epidermal homeostasis during aging remain poorly understood. To identify age-related microRNAs, a class of non-coding RNAs known to play a key role in the regulation of epidermal homeostasis, an exhaustive miRNA expression screen was performed in human keratinocytes from young or elderly subjects. Many microRNAs modulated by aging were identified, including miR-30a, in which both strands were overexpressed in aged cells and epidermal tissue. Read More

    Towards natural mimetics of metformin and rapamycin.
    Aging (Albany NY) 2017 Nov;9(11):2245-2268
    Insilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
    Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Read More

    T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.
    Aging (Albany NY) 2017 Nov;9(11):2436-2452
    Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark.
    Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. Read More

    Targeted elimination of senescent Ras-transformed cells by suppression of MEK/ERK pathway.
    Aging (Albany NY) 2017 Nov;9(11):2352-2375
    Institute of Cytology, Russian Academy of Sciences, St-Petersburg, Russia.
    The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance. Read More

    Transcriptome-wide association study of inflammatory biologic age.
    Aging (Albany NY) 2017 Nov;9(11):2288-2301
    National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA.
    Chronic low grade inflammation is a fundamental mechanism of aging. We estimated biologic age using nine biomarkers from diverse inflammatory pathways and we hypothesized that genes associated with inflammatory biological age would provide insights into human aging. In Framingham Offspring Study participants at examination 8 (2005 to 2008), we used the Klemera-Doubal method to estimate inflammatory biologic age and we computed the difference (∆Age) between biologic age and chronologic age. Read More

    Expression of a novel CNPY2 isoform in colorectal cancer and its association with oncologic prognosis.
    Aging (Albany NY) 2017 Nov;9(11):2334-2351
    Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
    Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Recently, we identified a novel biomarker, canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform2, and subsequently investigated its expression and prognostic value in CRC patients. We initially generated CNPY2 isoform2 monoclonal antibodies and examined CNPY2 isoform2 expression in CRC cell lines and tissues using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analyses. Read More

    Identification of new genetic variants of HLA-DQB1 associated with human longevity and lipid homeostasis-a cross-sectional study in a Chinese population.
    Aging (Albany NY) 2017 Nov;9(11):2316-2333
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
    Healthy longevity has been an unremitting pursuit of human, but its genetic and the environment causes are still unclear. As longevity population is a good healthy aging model for understanding how the body begin aging and the process of aging, and plasma lipids metabolism and balance is a very important to life maintain and physiologic functional turnover. It is important to explore how the effect of genetic variants associated long-life individuals on lipids metabolism and balance. Read More

    Psychological stress exposure to aged mice causes abnormal feeding patterns with changes in the bout number.
    Aging (Albany NY) 2017 Nov;9(11):2269-2287
    Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
    Stress responses are affected by aging. However, studies on stress-related changes in feeding patterns with aging subject are minimal. We investigated feeding patterns induced by two psychological stress models, revealing characteristics of stress-induced feeding patterns as "meal" and "bout" (defined as the minimum feeding behavior parameters) in aged mice. Read More

    SOCS1 regulates senescence and ferroptosis by modulating the expression of p53 target genes.
    Aging (Albany NY) 2017 Oct;9(10):2137-2162
    Département de Biochimie et Médecine Moléculaire; Université de Montréal, Montréal, Québec H3C 3J7, Canada.
    The mechanism by which p53 suppresses tumorigenesis remains poorly understood. In the context of aberrant activation of the JAK/STAT5 pathway, SOCS1 is required for p53 activation and the regulation of cellular senescence. In order to identify p53 target genes acting during the senescence response to oncogenic STAT5A, we characterized the transcriptome of STAT5A-expressing cells after SOCS1 inhibition. Read More

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