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      Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

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          Summary

          Recent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of micro RNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood micro RNA expression in 5221 adults and identified 127 micro RNAs that were differentially expressed by age at <  3.3 × 10 −4 (Bonferroni‐corrected). Most micro RNAs were underexpressed in older individuals. Integrative analysis of micro RNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated micro RNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘micro RNA age’ that incorporated expression levels of 80 micro RNAs. Micro RNA age correlated modestly with predicted age from DNA methylation ( =  0.3) and mRNA expression ( =  0.2), suggesting that micro RNA age may complement mRNA and epigenetic age prediction models. We used the difference between micro RNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, =  4.2 × 10 −5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a micro RNA age prediction model based on whole‐blood micro RNA expression profiling. Age‐associated micro RNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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          Cellular senescence in aging and age-related disease: from mechanisms to therapy.

          Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.
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            Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans.

            Many conditions that shift cells from states of nutrient utilization and growth to states of cell maintenance extend lifespan. We have carried out a systematic lifespan analysis of conditions that inhibit protein synthesis. We find that reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans. These perturbations, as well as inhibition of the nutrient sensor target of rapamycin (TOR), which is known to increase lifespan, all increase thermal-stress resistance. Thus inhibiting translation may extend lifespan by shifting cells to physiological states that favor maintenance and repair. Interestingly, different types of translation inhibition lead to one of two mutually exclusive outputs, one that increases lifespan and stress resistance through the transcription factor DAF-16/FOXO, and one that increases lifespan and stress resistance independently of DAF-16. Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis.
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              The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: design, recruitment, and initial examination.

              For nearly 60 years, the Framingham Heart Study has examined the natural history, risk factors, and prognosis of cardiovascular, lung, and other diseases. Recruitment of the Original Cohort began in 1948. Twenty-three years later, 3,548 children of the Original Cohort, along with 1,576 of their spouses, enrolled in the Offspring Cohort. Beginning in 2002, 4,095 adults having at least one parent in the Offspring Cohort enrolled in the Third Generation Cohort, along with 103 parents of Third Generation Cohort participants who were not previously enrolled in the Offspring Cohort. The objective of new recruitment was to complement phenotypic and genotypic information obtained from prior generations, with priority assigned to larger families. From a pool of 6,553 eligible individuals, 1,912 men and 2,183 women consented and attended the first examination (mean age: 40 (standard deviation: 9) years; range: 19-72 years). The examination included clinical and laboratory assessments of vascular risk factors and imaging for subclinical atherosclerosis, as well as assessment of cardiac structure and function. The comparison of Third Generation Cohort data with measures previously collected from the first two generations will facilitate investigations of genetic and environmental risk factors for subclinical and overt diseases, with a focus on cardiovascular and lung disorders.
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                Author and article information

                Contributors
                tianxiao.huan@nih.gov
                murabito@bu.edu
                levyd@nih.gov
                Journal
                Aging Cell
                Aging Cell
                10.1111/(ISSN)1474-9726
                ACEL
                Aging Cell
                John Wiley and Sons Inc. (Hoboken )
                1474-9718
                1474-9726
                17 October 2017
                February 2018
                : 17
                : 1 ( doiID: 10.1111/acel.2018.17.issue-1 )
                : e12687
                Affiliations
                [ 1 ] The Framingham Heart Study Framingham MA USA
                [ 2 ] The Population Sciences Branch Division of Intramural Research National Heart, Lung and Blood Institute National Institutes of Health Bethesda MD USA
                [ 3 ] Department of Computer Science and Engineering University of California San Diego CA USA
                [ 4 ] Department of Biostatistics Boston University School of Public Health Boston MA USA
                [ 5 ] Longitudinal Studies Section Translational Gerontology Branch Intramural Research Program National Institute on Aging National Institutes of Health Bethesda MD USA
                [ 6 ] Department of Medicine Section of General Internal Medicine Boston University School of Medicine Boston MA USA
                [ 7 ] Department of Medicine University of Massachusetts Medical School Worcester MA USA
                Author notes
                [*] [* ] Correspondence

                Tianxiao Huan, PhD and Daniel Levy, MD, Framingham Heart Study, Population Sciences Branch, National Heart, Lung, and Blood Institute, 73 Mt. Wayte Avenue, Suite 2, Framingham, MA 01702, USA . Tel.: +1 508 663 4084; fax: +1 508 935 3458 (TH) and Tel.: +1 508 935 3458; fax: +1 508 872 2678 (DL); e‐mails: tianxiao.huan@ 123456nih.gov and levyd@ 123456nih.gov

                and

                Joanne M. Murabito, MD, Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston, MA, USA . Tel.: +1 508 935 3461; fax: +1 508 626 1262; e‐mail: murabito@ 123456bu.edu

                Article
                ACEL12687
                10.1111/acel.12687
                5770777
                29044988
                b87fa889-812e-4624-a92c-329f6a83bfbb
                © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 September 2017
                Page count
                Figures: 4, Tables: 3, Pages: 10, Words: 9602
                Funding
                Funded by: National Institutes of Health
                Award ID: N01‐HC‐25195
                Award ID: HHSN268201500001I
                Funded by: Division of Intramural Research, National Heart, Lung, and Blood Institute
                Funded by: Center for Information Technology
                Award ID: R56AG029451
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                acel12687
                February 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.1 mode:remove_FC converted:17.01.2018

                Cell biology
                aging,cardiometabolic traits,methylation,microrna,mortality,mrna
                Cell biology
                aging, cardiometabolic traits, methylation, microrna, mortality, mrna

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