Extending life span by increasing oxidative stress.
Author information
- 1Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany. [email protected]
Abstract
Various nutritional, behavioral, and pharmacological interventions have been previously shown to extend life span in diverse model organisms, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mice, and rats, as well as possibly monkeys and humans. This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote increased formation of reactive oxygen species (ROS). These serve as molecular signals to exert downstream effects to ultimately induce endogenous defense mechanisms culminating in increased stress resistance and longevity, an adaptive response more specifically named mitochondrial hormesis or mitohormesis. Consistently, we here summarize findings that antioxidant supplements that prevent these ROS signals interfere with the health-promoting and life-span-extending capabilities of calorie restriction and physical exercise. Taken together and consistent with ample published evidence, the findings summarized here question Harman’s Free Radical Theory of Aging and rather suggest that ROS act as essential signaling molecules to promote metabolic health and longevity.
Copyright © 2011 Elsevier Inc. All rights reserved.
- PMID: 21619928 [PubMed – indexed for MEDLINE]
Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress.
Author information
- 1Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
Abstract
Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy. We show here that increased glucose availability decreases Caenorhabditis elegans life span, while impaired glucose metabolism extends life expectancy by inducing mitochondrial respiration. The histone deacetylase Sir2.1 is found here to be dispensable for this phenotype, whereas disruption of aak-2, a homolog of AMP-dependent kinase (AMPK), abolishes extension of life span due to impaired glycolysis. Reduced glucose availability promotes formation of reactive oxygen species (ROS), induces catalase activity, and increases oxidative stress resistance and survival rates, altogether providing direct evidence for a hitherto hypothetical concept named mitochondrial hormesis or “mitohormesis.” Accordingly, treatment of nematodes with different antioxidants and vitamins prevents extension of life span. In summary, these data indicate that glucose restriction promotes mitochondrial metabolism, causing increased ROS formation and cumulating in hormetic extension of life span, questioning current treatments of type 2 diabetes as well as the widespread use of antioxidant supplements.
Calorie restriction attenuates lipopolysaccharide (LPS)-induced microglial activation in discrete regions of the hypothalamus and the subfornical organ.
Author information
- 1School of Psychological Science, La Trobe University, Melbourne, VIC, Australia.
- 2School of Psychological Science, La Trobe University, Melbourne, VIC, Australia. Electronic address: [email protected].
Abstract
Calorie restriction (CR) has been shown to increase longevity and elicit many health promoting benefits including delaying immunosenescence and attenuating neurodegeneration in animal models of Alzheimer’s disease and Parkinson’s disease. CR also suppresses microglial activation following cortical injury and aging. We previously demonstrated that CR attenuates lipopolysaccharide (LPS)-induced fever and shifts hypothalamic signaling pathways to an anti-inflammatory bias; however, the effects of CR on LPS-induced microglial activation remain largely unexplored. The current study investigated regional changes in LPS-induced microglial activation in mice exposed to 50% CR for 28days. Immunohistochemistry was conducted to examine changes in ionized calcium-binding adapter molecule-1 (Iba1), a protein constitutively expressed by microglia, in a total of 27 brain regions involved in immunity, stress, and/or thermoregulation. Exposure to CR attenuated LPS-induced fever, and LPS-induced microglial activation in a subset of regions: the arcuate nucleus (ARC) and ventromedial nucleus of the hypothalamus (VMH) and the subfornical organ (SFO). Microglial activation in the ARC and VMH was positively correlated with body temperature. These data suggest that CR exerts effects on regionally specific populations of microglia; particularly, in appetite-sensing regions of the hypothalamus, and/or regions lacking a complete blood brain barrier, possibly through altered pro- and anti-inflammatory signaling in these regions.
Physical activity, stress reduction, and mood: insight into immunological mechanisms.
Author information
- 1Psychobiology Group, Department of Epidemiology and Public Health, University College London, London, UK. [email protected]
Abstract
Psychosocial factors, such as chronic mental stress and mood, are recognized as an important predictor of longevity and wellbeing. In particular, depression is independently associated with cardiovascular disease and all-cause mortality, and is often comorbid with chronic diseases that can worsen their associated health outcomes. Regular exercise is thought to be associated with stress reduction and better mood, which may partly mediate associations between depression, stress, and health outcomes. The underlying mechanisms for the positive effects of exercise on wellbeing remain poorly understood. In this overview we examine epidemiological evidence for an association between physical activity and mental health. We then describe the exercise withdrawal paradigm as an experimental protocol to study mechanisms linking exercise, mood, and stress. In particular we will discuss the potential role of the inflammatory response as a central mechanism.
- PMID: 22933142 [PubMed – indexed for MEDLINE]
Psychosocial stress and cardiovascular disease risk: the role of physical activity.
Author information
- Department of Epidemiology and Public Health, University College of London, UK. [email protected]
Abstract
Chronic stress and depression are associated with increased risk of cardiovascular disease and poorer prognosis, and physical (in)activity may be a key underlying biobehavioral mechanism. Physical activity has antidepressant effects, and physically fitter, more active individuals seem to be more biologically resilient to psychosocial stressors. This article will present data from a series of population cohort studies and laboratory-based psychophysiological studies to explore the role of physical activity as a protective factor against the effects of psychosocial stress on cardiovascular disease. These mechanisms may improve the treatment and prevention of stress-related illnesses and, thus, has important implications for public health and clinical care of high-risk patients.
- PMID: 23107839 [PubMed – indexed for MEDLINE]
Psychological risk factors and cardiovascular disease: is it all in your head?
Author information
- 1Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, LA 70121-2483, USA.
Abstract
Psychological stress has been shown to be associated with cardiovascular disease. Over the past few decades, there has been an increasing interest in this relationship, leading to a growing pool of clinical and epidemiological data on the subject. Psychological stress has multiple etiologies, which include behavioral causes, acute events or stressors, and/or chronic stress. Cardiac rehabilitation and exercise therapy have been shown to provide protection in primary and secondary coronary heart disease prevention, as well as improve overall morbidity and mortality. In this article, we review the available data regarding the association between psychological stress and cardiovascular disease, as well as the impact of cardiac rehabilitation and exercise therapy on psychological stress-related cardiovascular events.
- PMID: 21904099 [PubMed – indexed for MEDLINE]
The time has come for physicians to take notice: the impact of psychosocial stressors on the heart.
Author information
- Einstein Institute for Heart and Vascular Health, Albert Einstein Medical Center, and Jefferson Medical College, Philadelphia, Penn 19141, USA. [email protected]
Abstract
A rapidly growing body of evidence supports a relationship between psychosocial factors and cardiovascular disease. In this article, a review of the epidemiologic and clinical research investigating this relationship concludes that psychosocial stressors can be both a cause and a consequence of cardiovascular disease events. Furthermore, recent data have shown that stress management might reduce future cardiac events in patients with cardiovascular disease. Unfortunately, the influence of psychosocial risk factors on cardiovascular disease remains underrecognized compared with traditional cardiac risk factors. Physicians and their associates should screen for psychosocial stressors and recognize potential symptoms. Consideration should be given to developing improved liaison relationships with psychologic or behavioral specialists to facilitate more specialized interventions when appropriate. A variety of interventions conducted by appropriately trained mental health professionals have successfully improved stress in patients with cardiovascular disease and other chronic diseases. The time has come for physicians to recognize the impact of psychosocial stressors on cardiovascular disease.
- PMID: 19635269 [PubMed – indexed for MEDLINE]
Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.
Author information
- 1Division of Cardiology, Department of Medicine, St Luke’s/Roosevelt Hospital Center, New York, NY 10025, USA. [email protected]
Abstract
Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient “alternative” end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.
Comment in
- Psychological factors and ischemic heart disease. [Circulation. 2000]
Emotional Reactivity and Mortality: Longitudinal Findings From the VA Normative Aging Study.
Author information
- 1Correspondence should be addressed to Dan Mroczek, Department of Psychology, Northwestern University, Swift Hall, 2029 Sheridan Road, Evanston, IL 60208. E-mail: [email protected].
Abstract
Objectives.Evidence suggests a predictive association between emotion and mortality risk. However, no study has examined dynamic aspects of emotion in relation to mortality. This study used an index of emotional reactivity, defined as changes in positive or negative affect in response to daily stressors, to predict 10-year survival.
METHODS:
An 8-day daily diary study was conducted in 2002 on 181 men aged 58-88. Multilevel models were employed to estimate emotional reactivity coefficients, which were subsequently entered into a Cox proportional hazards model to predict mortality.
RESULTS:
Results indicated that positive emotional reactivity, that is, greater decreases in positive affect in response to daily stressors, increased mortality risk. Negative emotional reactivity did not predict mortality.Discussion.Findings highlight the potential importance of dynamic aspects of positive affect in prediction of physical health outcomes such as mortality.
KEYWORDS:
Emotion, Emotion Regulation, Longevity, Personality, Quantitative Methods
- PMID: 24170714 [PubMed – as supplied by publisher]
Investigating the effects of conscientiousness on daily stress, affect and physical symptom processes: A daily diary study.
Author information
- 1Institute of Psychological Sciences, University of Leeds, UK.
Abstract
OBJECTIVES:
Higher conscientiousness (C) predicts better health outcomes. Recent research suggests that stress may play an important role in explaining this relationship. The current study aimed to establish whether C moderates the relationship between daily hassle appraisals, daily affect, and physical symptoms.
DESIGN AND METHODS:
A daily diary design was used, where participants (N = 103) completed a baseline measure of C followed by a 14-day daily diary, providing daily details of hassles (primary and secondary appraisals) experienced as well as positive and negative affect and physical symptoms.
RESULTS:
Hierarchical linear modelling revealed that Total C (as well as two facets of C: Order and Industriousness) moderated the relationship between stress appraisals and positive affect. Specifically, the negative association between the daily appraisal of hassles as stressful (i.e., where perceived demands outweighed perceived resources) and positive affect was stronger for lower and average levels of C, Order, and Industriousness. No significant moderated effects were found for negative affect or physical symptoms. The Order facet was also found to be an important factor predicting attrition.
CONCLUSIONS:
The current study provided evidence that C and two of its facets can moderate the relationship between hassle appraisal and positive affect. C may exert part of its influence on health by modifying the effects of daily stressors.
STATEMENT OF CONTRIBUTION:
What is already known on this subject? Conscientiousness has a significant positive effect on longevity and health status. While the performance of health behaviours may partially account for this relationship, evidence suggests that it does not fully mediate the effect. Research has begun to look at stress as a possible additional explanatory variable, and there is evidence that Conscientiousness moderates the relationship between stress and health behaviours. What does this study add? Shows that Conscientiousness and two of its facets (Order and Industriousness) moderate the relationship between hassle appraisal and positive affect. Highlights the importance of studying lower order facets of personality in health research. Suggests that Conscientiousness may exert part of its influence on health by modifying the effects of daily stressors.
© 2013 The British Psychological Society.
KEYWORDS: Affect, Attrition, Daily Diaries, Hassles, Multilevel modelling, Personality, Stress
- PMID: 24237707 [PubMed – as supplied by publisher]
Investigating the effects of conscientiousness on daily stress, affect and physical symptom processes: A daily diary study.
Author information
- 1Institute of Psychological Sciences, University of Leeds, UK.
Abstract
OBJECTIVES:
Higher conscientiousness (C) predicts better health outcomes. Recent research suggests that stress may play an important role in explaining this relationship. The current study aimed to establish whether C moderates the relationship between daily hassle appraisals, daily affect, and physical symptoms.
DESIGN AND METHODS:
A daily diary design was used, where participants (N = 103) completed a baseline measure of C followed by a 14-day daily diary, providing daily details of hassles (primary and secondary appraisals) experienced as well as positive and negative affect and physical symptoms.
RESULTS:
Hierarchical linear modelling revealed that Total C (as well as two facets of C: Order and Industriousness) moderated the relationship between stress appraisals and positive affect. Specifically, the negative association between the daily appraisal of hassles as stressful (i.e., where perceived demands outweighed perceived resources) and positive affect was stronger for lower and average levels of C, Order, and Industriousness. No significant moderated effects were found for negative affect or physical symptoms. The Order facet was also found to be an important factor predicting attrition.
CONCLUSIONS:
The current study provided evidence that C and two of its facets can moderate the relationship between hassle appraisal and positive affect. C may exert part of its influence on health by modifying the effects of daily stressors.
STATEMENT OF CONTRIBUTION:
What is already known on this subject? Conscientiousness has a significant positive effect on longevity and health status. While the performance of health behaviours may partially account for this relationship, evidence suggests that it does not fully mediate the effect. Research has begun to look at stress as a possible additional explanatory variable, and there is evidence that Conscientiousness moderates the relationship between stress and health behaviours. What does this study add? Shows that Conscientiousness and two of its facets (Order and Industriousness) moderate the relationship between hassle appraisal and positive affect. Highlights the importance of studying lower order facets of personality in health research. Suggests that Conscientiousness may exert part of its influence on health by modifying the effects of daily stressors.
© 2013 The British Psychological Society.