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      Obesity and ageing: Two sides of the same coin

      1 , 2 , 1 , 3 , 1 , 2 , 4
      Obesity Reviews
      Wiley

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          Most cited references153

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          Patterns of somatic mutation in human cancer genomes.

          Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.
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            Is Open Access

            An epigenetic biomarker of aging for lifespan and healthspan

            Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
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              Excess deaths associated with underweight, overweight, and obesity.

              As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. To estimate deaths associated with underweight (body mass index [BMI] or =30) in the United States in 2000. We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) I (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES III (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. Number of excess deaths in 2000 associated with given BMI levels. Relative to the normal weight category (BMI 18.5 to or =30) was associated with 111,909 excess deaths (95% confidence interval [CI], 53,754-170,064) and underweight with 33,746 excess deaths (95% CI, 15,726-51,766). Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease.
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                Author and article information

                Journal
                Obesity Reviews
                Obesity Reviews
                Wiley
                1467-7881
                1467-789X
                February 05 2020
                February 05 2020
                Affiliations
                [1 ]Department of Health, Kinesiology, and Applied PhysiologyConcordia University Quebec Montreal Canada
                [2 ]Metabolism, Obesity, and Nutrition Lab, PERFORM CentreConcordia University Quebec Montreal Canada
                [3 ]Division of Geriatric Medicine and Research InstituteMcGill University Health Centre Quebec Montreal Canada
                [4 ]Research Centre, Centre intégré universitarie de santé et de services sociaux du Nord‐de‐I'Île‐de‐MontréalHôpital du Sacré‐Cœur de Monréal (CIUSS‐NIM, HSCM) Quebec Montreal Canada
                Article
                10.1111/obr.12991
                32020741
                0d53a7bc-1f40-4055-a900-a8fb3c82b3f4
                © 2020

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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