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      n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease

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          Abstract

          DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F 2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids ( p = 0.015). Post-intervention plasma F 2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count ( p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.

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          Gene regulation and DNA damage in the ageing human brain.

          The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by induction of stress response, antioxidant and DNA repair genes. DNA damage is markedly increased in the promoters of genes with reduced expression in the aged cortex. Moreover, these gene promoters are selectively damaged by oxidative stress in cultured human neurons, and show reduced base-excision DNA repair. Thus, DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a programme of brain ageing that starts early in adult life.
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            Telomeres, lifestyle, cancer, and aging.

            There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening. Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases. Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging.
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              Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance.

              Telomeres are the DNA-protein complexes that protect the ends of eukaryotic chromosomes. The cellular enzyme telomerase counteracts telomere shortening by adding telomeric DNA. A growing body of literature links shorter telomere length and lower telomerase activity with various age-related diseases and earlier mortality. Thus, leukocyte telomere length (LTL) and telomerase activity are emerging both as biomarkers and contributing factors for age-related diseases. However, no clinical study has directly examined telomerase activity and telomere length in different lymphocyte subtypes isolated from the same donors, which could offer insight into the summary measure of leukocyte telomere maintenance. We report the first quantitative data in humans examining both levels of telomerase activity and telomere length in four lymphocyte subpopulations from the same donors-CD4+, CD8+CD28+ and CD8+CD28- T cells and B cells, as well as total PBMCs-in a cohort of healthy women. We found that B cells had the highest telomerase activity and longest telomere length; CD4+ T cells had slightly higher telomerase activity than CD8+CD28+ T cells, and similar telomere length. Consistent with earlier reports that CD8+CD28- T cells are replicatively senescent cells, they had the lowest telomerase activity and shortest telomere length. In addition, a higher percentage of CD8+CD28- T cells correlated with shorter total PBMC TL (r=-0.26, p=0.05). Interestingly, telomerase activities of CD4+ and CD8+CD28+ T cells from the same individual were strongly correlated (r=0.55, r<0.001), indicating possible common mechanisms for telomerase activity regulation in these two cell subtypes. These data will facilitate the understanding of leukocyte aging and its relationship to human health. Copyright 2009 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                19 March 2016
                March 2016
                : 8
                : 3
                : 175
                Affiliations
                [1 ]School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth 6000, Western Australia, Australia; valerie.burke@ 123456uwa.edu.au (V.B.); emilie.mas@ 123456sa.gov.au (E.M.); lawrie.beilin@ 123456uwa.edu.au (L.J.B.); gerald.watts@ 123456uwa.edu.au (G.F.W.); ian.puddey@ 123456uwa.edu.au (I.B.P.); trevor.mori@ 123456uwa.edu.au (T.A.M.)
                [2 ]CSIRO Food and Nutrition, Adelaide 5000, South Australia, Australia; nathan.OCallaghan@ 123456csiro.au (N.O.C.); Michael.Fenech@ 123456csiro.au (M.F.)
                [3 ]Department of Nephrology and Transplantation, Fiona Stanley Hospital, Murdoch 6150, Western Australia, Australia; Ashley.Irish@ 123456health.wa.gov.au
                [4 ]Telethon Kids Institute, Subiaco 6008, Western Australia, Australia; Rae-Chi.Huang@ 123456telethonkids.org.au
                Author notes
                [* ]Correspondence: anne.barden@ 123456uwa.edu.au ; Tel.: +61-8-9224-0272
                [†]

                These authors contributed equally to this work.

                Article
                nutrients-08-00175
                10.3390/nu8030175
                4808901
                27007392
                fa27e9ba-afcf-417f-83c9-e2e82daba0af
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 December 2015
                : 17 March 2016
                Categories
                Article

                Nutrition & Dietetics
                neutrophils,telomere length,oxidative stress,n-3 fatty acids,coenzyme q10
                Nutrition & Dietetics
                neutrophils, telomere length, oxidative stress, n-3 fatty acids, coenzyme q10

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