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    Targeted elimination of senescent Ras-transformed cells by suppression of MEK/ERK pathway.
    Aging (Albany NY) 2017 Nov 14. Epub 2017 Nov 14.
    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 11. Epub 2017 Nov 11.
    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 13. Epub 2017 Nov 13.
    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 10. Epub 2017 Nov 10.
    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. Epub 2017 Nov 9.
    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

    SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy.
    Aging (Albany NY) 2017 Oct;9(10):2163-2189
    Institut für Biochemie und Molekularbiologie II, Medizinische Fakultät der Heinrich-Heine-Universität, Düsseldorf, Germany.
    The stress-responsive mitochondrial sirtuin SIRT4 controls cellular energy metabolism in a NAD(+)-dependent manner and is implicated in cellular senescence and aging. Here we reveal a novel function of SIRT4 in mitochondrial morphology/quality control and regulation of mitophagy. We report that moderate overexpression of SIRT4, but not its enzymatically inactive mutant H161Y, sensitized cells to mitochondrial stress. Read More

    A new mutation-independent approach to cancer therapy: Inhibiting oncogenic RAS and MYC, by targeting mitochondrial biogenesis.
    Aging (Albany NY) 2017 Oct;9(10):2098-2116
    Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester, UK.
    Here, we used MCF7 cells as a model system to interrogate how MYC/RAS co-operativity contributes to metabolic flux and stemness in breast cancer cells. We compared the behavior of isogenic MCF7 cell lines transduced with c-Myc or H-Ras (G12V), either individually or in combination. Cancer stem cell (CSC) activity was measured using the mammosphere assay. Read More

    Degeneration of the osteocyte network in the C57BL/6 mouse model of aging.
    Aging (Albany NY) 2017 Oct;9(10):2190-2208
    Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri Kansas City, Kansas City, MO 64108, USA.
    Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Read More

    Thyroid status and mortality in nonagenarians from long-lived families and the general population.
    Aging (Albany NY) 2017 Oct;9(10):2223-2234
    Department of Internal Medicine, section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Zuid-Holland, 2300 RC, the Netherlands.
    The relationship between thyroid status and longevity has been investigated extensively. However, data on thyroid status and survival in old age is scarce. In this study we investigated associations of different parameters of thyroid status with mortality in nonagenarians, and whether these associations were different in nonagenarians from long-lived families than in nonagenarians from the general population. Read More

    Senescence-associated ultrastructural features of long-term cultures of induced pluripotent stem cells (iPSCs).
    Aging (Albany NY) 2017 Oct;9(10):2209-2222
    Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Bambino Gesu' Children's Research Hospital, IRCCS, Rome 00146, Italy.
    Induced pluripotent stem cells (iPSCs) hold great promise for developing personalized regenerative medicine, however characterization of their biological features is still incomplete. Moreover, changes occurring in long-term cultured iPSCs have been reported, suggesting these as a model of cellular aging. For this reason, we addressed the ultrastructural characterization of iPSCs, with a focus on possible time-dependent changes, involving specific cell compartments. Read More

    Identification of polymorphisms in cancer patients that differentially affect survival with age.
    Aging (Albany NY) 2017 Oct;9(10):2117-2136
    Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, United Kingdom.
    The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic variants affect cancer progression commonly neglects to account for the ageing process. Read More

    Age-related decline of the acute local inflammation response: a mitigating role for the adenosine A2A receptor.
    Aging (Albany NY) 2017 Oct;9(10):2083-2097
    Faculty of Medicine, and Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Canada.
    Aging is accompanied by an increase in markers of innate immunity. How aging affects neutrophil functions remains of debate.The adenosine A2A receptor (A2AR), essential to the resolution of inflammation, modulates neutrophil functions. Read More

    Natural product celastrol suppressed macrophage M1 polarization against inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and NF-κB pathways.
    Aging (Albany NY) 2017 Oct;9(10):2069-2082
    School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
    Macrophage polarization is implicated in the inflammation in obesity. The aim of the present study was to examine the anti-inflammatory activities of botanical triterpene celastrol against diet-induced obesity. We treated diet-induced obese C57BL/6N male mice with celastrol (5, 7. Read More

    PKCζ-dependent upregulation of p27kip1 contributes to oxidative stress induced retinal pigment epithelial cell multinucleation.
    Aging (Albany NY) 2017 Oct;9(10):2052-2068
    Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, BT97 BL, UK.
    Retinal pigment epithelial (RPE) cells increase in size and multinucleate during aging. We have shown using human and mouse cell lines that oxidised photoreceptor outer segments (oxPOS)-induced cytokinesis failure is related to RPE cell multinucleation, although the underlying mechanism remains unknown. This study investigated the role of the PKC pathway in oxPOS-induced RPE multinucleation using ARPE19 cells. Read More

    Age-related gene expression in luminal epithelial cells is driven by a microenvironment made from myoepithelial cells.
    Aging (Albany NY) 2017 Oct;9(10):2026-2051
    Department of Population Sciences, City of Hope, Duarte, CA, 91010, USA.
    Luminal epithelial cells in the breast gradually alter gene and protein expression with age, appearing to lose lineage-specificity by acquiring myoepithelial-like characteristics. We hypothesize that the luminal lineage is particularly sensitive to microenvironment changes, and age-related microenvironment changes cause altered luminal cell phenotypes. To evaluate the effects of different microenvironments on the fidelity of epigenetically regulated luminal and myoepithelial gene expression, we generated a set of lineage-specific probes for genes that are controlled through DNA methylation. Read More

    Leukocyte telomere length, T cell composition and DNA methylation age.
    Aging (Albany NY) 2017 Sep;9(9):1983-1995
    Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA.
    Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age─ the extrinsic epigenetic age acceleration (EEAA)─ is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. Read More

    Large-scale replication study identified multiple independent SNPs in RET synergistically associated with Hirschsprung disease in Southern Chinese population.
    Aging (Albany NY) 2017 Sep;9(9):1996-2009
    Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.
    Hischsprung disease (HSCR) is an intestinal disorder with strong genetic components. RET was considered as the strongest contributor. Multiple single nucleotide polymorphisms (SNP) were demonstrated as associated with HSCR in different populations. Read More

    The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons.
    Aging (Albany NY) 2017 Sep;9(9):1957-1970
    Department of Neurobiology and Anatomy, the University of Texas McGovern Medical School at Houston, TX 77030, USA.
    The G-quadruplex is a non-canonical DNA secondary structure formed by four DNA strands containing multiple runs of guanines. G-quadruplexes play important roles in DNA recombination, replication, telomere maintenance, and regulation of transcription. Small molecules that stabilize the G-quadruplexes alter gene expression in cancer cells. Read More

    Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging.
    Aging (Albany NY) 2017 Sep;9(9):1971-1982
    Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
    Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. Read More

    Epigenetic silencing of miR-338 facilitates glioblastoma progression by de-repressing the pyruvate kinase M2-β-catenin axis.
    Aging (Albany NY) 2017 Aug;9(8):1885-1897
    Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
    Glioblastoma is the most malignant type of brain tumor, and its high invasiveness and multiplication severely shortens patients' overall survival. The embryonic pyruvate kinase M2 (PKM2) isoform is highly expressed in human cancer. We used computational target gene prediction, in vitro cell culture, immunoblotting, quantitative real-time PCR, ATP measurements, luciferase reporter assays, wound-healing assays, Transwell assays, RNA immunoprecipitation PCR, co-immunoprecipitation, flow cytometry and tumor xenografts to study the regulation of the PKM2/β-catenin axis in glioma. Read More

    MortalityPredictors.org: a manually-curated database of published biomarkers of human all-cause mortality.
    Aging (Albany NY) 2017 Aug;9(8):1916-1925
    BioAge Labs, Berkeley, CA 94703, USA.
    Biomarkers of all-cause mortality are of tremendous clinical and research interest. Because of the long potential duration of prospective human lifespan studies, such biomarkers can play a key role in quantifying human aging and quickly evaluating any potential therapies. Decades of research into mortality biomarkers have resulted in numerous associations documented across hundreds of publications. Read More

    Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells.
    Aging (Albany NY) 2017 Aug;9(8):1898-1915
    Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.
    Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFP(Low)), activatable reserve IESC and enteroendocrine cells (Sox9-EGFP(High)), Sox9-EGFP(Sublow) progenitors, and Sox9-EGFP(Negative) differentiated lineages. Read More

    Chronic exercise reduces hypothalamic transforming growth factor-β1 in middle-aged obese mice.
    Aging (Albany NY) 2017 Aug;9(8):1926-1940
    School of Applied Sciences, University of Campinas, Limeira, SP, Brazil.
    Obesity and aging are associated with hypothalamic inflammation, hyperphagia and abnormalities in the thermogenesis control. It has been demonstrated that the association between aging and obesity induces hypothalamic inflammation and metabolic disorders, at least in part, through the atypical hypothalamic transforming growth factor-β (TGF-β1). Physical exercise has been used to modulate several metabolic parameters. Read More

    Aging and calorie restriction regulate the expression of miR-125a-5p and its target genes Stat3, Casp2 and Stard13.
    Aging (Albany NY) 2017 Jul;9(7):1825-1843
    Center for Gene Regulation in Health and Disease and Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.
    Calorie restriction (CR) is a dietary intervention known to delay aging. In order, to understand molecular mechanisms of CR, we analyzed the expression of 983 MicroRNAs (miRNAs) in the liver of female mice after 2 years of 30% CR using micro-array. 16 miRNAs demonstrated significant changes in their expression upon CR in comparison with age-matched control. Read More

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