Shorter telomeres have been associated with poor health behaviors, age-related diseases, and early mortality. Telomere length is regulated by the enzyme telomerase, and is linked to exposure to proinflammatory cytokines and oxidative stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation lowered the concentration of serum proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length, telomerase, and oxidative stress. In addition to testing for group differences, changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence, absorption, and metabolism. The double-blind 4-month trial included 106 healthy sedentary overweight middle-aged and older adults who received (1) 2.5 g/day n-3 PUFAs, (2) l.25 g/day n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values were 15% lower in the two supplemented groups compared to placebo. Although group differences for telomerase and telomere length were nonsignificant, changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention’s impact: telomere length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions. This translational research broadens our understanding of the potential impact of the n-6:n-3 PUFA balance. ClinicalTrials.gov identifier: NCT00385723
Observational studies have linked lower levels of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) with inflammation and depression. This study was designed to determine whether n-3 supplementation would decrease serum cytokine production and depressive symptoms in 138 healthy middle-aged and older adults (average age=51.04, SD=7.76) who were sedentary and overweight (average BMI=30.59, SD= 4.50). This three-arm randomized, placebo-controlled, double-blind 4-month trial compared responses to (1) 2.5 g/d n-3 PUFAs, or (2) 1.25 g/d n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Serum interleukin-6 decreased by 10% and 12% in our low and high dose n-3 groups, respectively, compared to a 36% increase in the placebo group. Similarly, low and high dose n-3 groups showed modest 0.2% and −2.3% changes in serum tumor necrosis factor alpha, compared to a 12% increase in the control group. Depressive symptoms were quite low at baseline and did not change significantly in response to supplementation. Our data suggest that n-3 PUFAs can reduce inflammation in overweight, sedentary middle-aged and older adults, and thus could have broad health benefits. These data provide a window into the ways in which the n-3 PUFAs may impact disease initiation, progression, and resolution. ClinicalTrials.gov identifier: NCT00385723
Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. This study evaluated relationships between fatigue and both sympathetic and parasympathetic nervous system activity in breast cancer survivors. Norepinephrine and heart rate variability (HRV) were evaluated at rest, as well as during and after a standardized laboratory speech and mental arithmetic stressor. The participants, 109 women who had completed treatment for stage 0-IIIA breast cancer within the past two years, were at least two months post surgery, radiation or chemotherapy, whichever occurred last. Women who reported more fatigue had significantly higher norepinephrine and lower HRV before and after the stressor than their less fatigued counterparts. Fatigue was not related to treatment or disease variables including treatment type, cancer stage, time since diagnosis, and time since treatment. Importantly, the relationship between HRV and cancer-related fatigue was sizeable. Based on research that has demonstrated characteristic age-related HRV decrements, our findings suggest a 20 year difference between fatigued and non-fatigued cancer survivors, raising the possibility that fatigue may signify accelerated aging. Furthermore, lower HRV and elevated norepinephrine have been associated © 2011 Elsevier Ltd. All rights reserved. * Corresponding Author: Janice K. Kiecolt-Glaser, PhD Institute for Behavioral Medicine Research Ohio State University College of Medicine 460 Medical Center Drive, Room 130C Columbus, OH 43210-1228 USA Phone: Janice.Kiecolt-Glaser@osumc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptPsychoneuroendocrinology. Author manuscript; available in PMC 2012 September 1. with a number of adverse health outcomes; accordingly, fatigue may also signal the need for increased vigilance to other health threats. KeywordsVagal tone; respiratory sinus arrhythmia; heart rate variability; autonomic nervous system; norepinephrine; breast cancerFatigue is the most common problem among long-term cancer survivors (Bower et al., 2006a), as well as the symptom that interferes most with their daily life (Cleeland et al., 2003;Ganz et al., 2002). Fatigue adversely affects overall quality of life, as well as many daily activities including mood, the sleep-wake cycle, and personal relationships (Bower et al., 2002;Collado-Hidalgo et al., 2006;Lawrence et al., 2004). Fatigue is a normal and expected response to chemotherapy and radiation (Smets et al., 1993). However, fatigue may persist many years beyond cancer...
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