Caloric restriction and oxidative stress -
Gredilla R , Sanz A , López-Torres M , Barja G Caloric restriction decreases mitochondrial free radical generation al complex I and lowers oxidative damage to mitochondrial DNA in the rat heart.
FASEB J 15 : — López-Torres M , Gredilla R , Sanz A , Barja G Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria.
Free Radical Biol Med 32 : — Drew B , Phaneuf S , Dirks A , Selman C , Gredilla R , Lezza A , Barja G , Leeuwenburgh C Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart.
Am J Physiol : R — R Sanz A , Caro P , Gredilla R , Barja G Dietary restriction at old age lowers mitochondrial oxygen radical production and leak at complex I and oxidative DNA damage in rat brain. J Bioenerg Biomembr 37 : 83 — Yu BP Aging and oxidative stress: modulation by dietary restriction.
Free Radical Biol Med 21 : — Leon TI , Lim BO , Yu BP , Lim Y , Jeon EJ , Park DK Effect of dietary restriction on age-related increase of liver susceptibility to peroxidation in rats. Lipids 36 : — Judge S , Judge A , Grune T , Leeuwenburgh C Short-term CR decreases cardiac mitochondrial oxidant production but increases carbonyl content.
Lee CK , Klopp RG , Weindruch R , Prolla TA Gene expression profile of ageing and its retardation by caloric restriction. Dhabi JM , Mote PL , Wingo J , Rowley BC , Cao SX , Walford RL , Spindler SR Caloric restriction alters the feeding response of key metabolic enzyme genes.
Mech Aging Dev : — Selbsty J , Judge AR , Yimlamai T , Leeuwenburgh C , Dodd SL Life long calorie restriction increases heat shock proteins and proteasome activity in soleus muscle of Fisher rats.
Exp Gerontol 40 : 37 — Stuart JA , Karahalil B , Hogue BA , Souza-Pinto NC , Bohr VA Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction. FASEB J 18 : — Barja G Endogenous oxidative stress: relationship to aging, longevity and caloric restriction.
Ageing Res Rev 1 : — Curr Opin Genet Dev 11 : — Bartke A , Brown-Borg H Life extension in the dwarf mouse. Curr Top Dev Biol 63 : — Bartke A , Wright JC , Mattison JA , Ingram DK , Miller RA , Roth GS Extending the lifespan of long-lived mice.
Nature : Lambert AJ , Merry BJ Effect of caloric restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin. Am J Physiol : R71 — R Lambert AJ , Wang B , Merry BJ Exogenous insulin can reverse the effects of caloric restriction on mitochondria. Biochem Biophys Res Commun : — Sanz A , Gredilla R , Pampona R , Portero-Otin M , Vara E , Tresguerres JAF , Barja G Effect of insulin and growth hormone on rat heart and liver oxidative stress in control and caloric restricted animals.
Biogerontology 6 : 15 — Exp Gerontol 38 : — Sabatino F , Masoro EJ , McMahan CA , Kuhn RW Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. J Gerontol 46 : B — B Masoro EJ , Austad SN The evolution of the antiaging action of dietary restriction: a hypothesis.
J Gerontol Biol Sci 51A : B — B Patel NV , Finch CE The glucocorticoid paradox of caloric restriction in slowing brain aging. Neurobiol Aging 23 : — Sohal RS , Ku HH , Agarwal S , Forster MJ , Lal H Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse.
Mech Ageing Dev 74 : — Gredilla R , Barja G , López-Torres M Effect of short-term caloric restriction on H 2 O 2 production and oxidative DNA damage in rat liver mitochondria, and location of the free radical source.
J Bioenerg Biomembr 33 : — Gredilla R , López-Torres M , Barja G Effect of time of restriction on the decrease in mitochondrial H2O2 production and oxidative DNA damage in the heart of food-restricted rats.
Ramsey JJ , Hagopian K , Kenny TM , Koomson EK , Bevilacqua L , Weindruch R , Harper ME Proton leak and hydrogen peroxide production in liver mitochondria from energy-restricted rats. Am J Physiol : E31 — E Bevilacqua L , Ramsey JJ , Hagopian K , Weindruch R , Harper ME Effects of short- and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production.
Am J Physiol : E — E Gredilla R , Phaneuf S , Selman C , Kendaiah S , Leeuwenburgh C , Barja G Short-term caloric restriction and sites of oxygen radical generation in kidney and skeletal muscle mitochondria.
Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
Sign In or Create an Account. Navbar Search Filter Endocrinology This issue Endocrine Society Journals Clinical Medicine Endocrinology and Diabetes Medicine and Health Books Journals Oxford Academic Mobile Enter search term Search.
Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract.
Caloric Restriction and Mitochondrial Oxidative Stress. Eating Less, Living Longer: Underlying Mechanisms. Hormonal Pathways and CR Effects. Journal Article.
Minireview: The Role of Oxidative Stress in Relation to Caloric Restriction and Longevity. Ricardo Gredilla , Ricardo Gredilla. Oxford Academic. Gustavo Barja. Gustavo Barja, Departamento de Fisiología Animal II, Facultad de Biología, Universidad Complutense de Madrid, José Antonio Novais 2, Madrid , Spain.
PDF Split View Views. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter Endocrinology This issue Endocrine Society Journals Clinical Medicine Endocrinology and Diabetes Medicine and Health Books Journals Oxford Academic Enter search term Search.
Abstract Reduction of caloric intake without malnutrition is one of the most consistent experimental interventions that increases mean and maximum life spans in different species. TABLE 1. Brain Heart Skeletal muscle Liver Open in new tab. TABLE 2. CR effect on Mt ROS generation.
TABLE 3. First Published Online May 26, The effect of retarded growth upon the length of the life-span and ultimate body size. Google Scholar OpenURL Placeholder Text. Google Scholar Crossref.
Search ADS. Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Genotype and age influence the effect of caloric intake on mortality in mice.
Google Scholar PubMed. OpenURL Placeholder Text. Effect of dietary restriction beyond middle age: accumulation of altered proteins and protein degradation. Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts.
The effect of low protein-high dextrin diet and subsequent food restriction upon life prolongation in Fischer male rats. Protein restriction without strong caloric restriction decreases mitochondrial oxygen radical production and oxidative DNA damage in rat liver.
Free radical theory of aging: increasing the average of life expectancy at birth and the maximum life span.
Mitochondrial free radical generation: sites of production in states 4 and 3, organ specificity and relationship with aging rate. Aging in vertebrates, and the effect of caloric restriction: a mitochondrial free radical production-DNA damage mechanism?
Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation? Each participant received a written list of foods at daily pick-up. Any uneaten foods and any additional foods eaten by the participants were reported on sheets collected daily.
The study dietitian met with each participant weekly to discuss the diet, resolve any barriers or concerns related to food or specimen collection, and encourage compliance.
Energy and nutrient intake calculations were performed using the Nutrient Data System for Research NDSR software version developed by the Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN, Food and Nutrient Database [20] , [21].
Adherence to the protocol was monitored by urinary biomarkers sodium, potassium, nitrogen [22] , [23]. Participants in the control group were asked to follow their habitual diet for the study duration and they received a multivitamin supplement daily Nature Made, Mission Hills, CA.
Their dietary intake was assessed during the intervention Days 1—28 from three dietary recalls 2 weekdays and 1 weekend day performed using automated multi-pass method and NDS-R software [24] , [25]. Daily physical activity was assessed using an RT3 accelerometer StayHealthy, Monrovia, CA, US.
Participants were instructed to maintain their habitual physical activity level and wore an activity monitor on their right hip while awake for the duration of the intervention and twice for 7 days during the follow-up. Total and physical activity energy expenditure was calculated using energy calculated from the monitor-measured movement and measured REE.
Physical activity levels PAL for each monitored day were calculated by dividing total energy expenditure by REE.
Blood pressure was measured 3 times a week in the reclining position after 10 min rest with automatically inflating cuff Dynamap, General Electric, Milwaukee, WI, USA using a standard protocol. Venous blood samples were drawn after an overnight fast at baseline and on days 1, 3, 5, 7, 14, 21, 29, 42, and , centrifuged immediately at 1 g for 10 minutes at 4°C, and the serum was stored in cryovials at —80°C until the assays were performed in batches.
Samples obtained at baseline and during the study for each participant were included in the same assay run to avoid inter-assay variability among participants. F 2 -isoprostane assessing oxidation of lipids [29] has been shown to provide one of the most accurate assessments of oxidative stress status [27] , [30].
Other methods not used in this study are targeting protein oxidation by measuring carbonyl groups in serum [31] , DNA damage by measuring hydroxyl radical-induced products of DNA bases [32] , and activity of several antioxidative enzymes including catalase, superoxide dismutase SOD , glutathione S-transferase, and glutathione peroxidase GPx [33] — [35].
A basic metabolic panel, hematological indices hemoglobin concentration, hematocrit, red and white blood cell counts , and C-reactive protein were analyzed in the Vanderbilt University Hospital Laboratory using standard methodologies.
Plasma triglyceride TG , total cholesterol TC , low-density lipoprotein LDL , and high-density lipoprotein HDL levels were measured using enzymatic kits from Cliniqa Corporation San Marcos, CA.
Free fatty acids FFA were measured using the NEFA-C kit by Wako Nneuss, Germany and by gas chromatography. Glucose was measured using the Vitros Chemistry analyzer. Insulin and leptin measurements were performed using RIAs.
Adiponectin was measured using a kit from Millipore Billerica, MA and Luminex multiplexing technology. Complete h urine samples were collected once weekly.
Urinary calcium, sodium, and potassium were measured using Vitros Analyzer Ortho-Clinical Diagnostics, Rochester, NY, USA. Urinary nitrogen content was measured using nitrogen analyzer Antek Instrument Nitrogen System NS, Antek Instruments, Inc. The nitrogen excretion in the urine was used as a biological marker for protein intake by multiplying the content of nitrogen in the urine by the factor 7.
The urine sodium and potassium contents were used as biological markers of sodium and potassium intake, respectively. Urinary creatinine was measured on a Sirrus Clinical Chemistry analyzer Stanbio Laboratory, Boerne, TX. Descriptive statistics were presented as mean and standard deviation SD or median and IQR or percentage, as appropriate.
Daily caloric intake and REE were expressed as the absolute and deficit number of kilocalories per day. Continuous endpoints were compared between the control and intervention group using Wilcoxon rank sum test. The change within group was assessed using Wilcoxon signed rank test. Spearman correlation coefficient was used to assess the correlation between two continuous variables.
Multivariable linear model was used to assess the treatment effect at single time point while adjusting for the baseline measures.
We performed a linear model using generalized least squares with autocorrelation structure of order 1 AR1 for the within-subject correlation to assess the F 2 -isoprostane change within 28 days of study period.
The main effects included baseline age, BMI, and F 2 -isoprostane, time, group, and time by group interaction. Time was modeled as nonlinear relationship to the F 2 -isoprostane using restricted cubic splines. Residual plot and quantile-quantile QQ plots were used to check the model assumptions.
All analyses were done with STATA 11 StataCorp, College Station, TX and the statistical programming language R, version 2.
Thirty of 32 participants in the CR group and all controls completed the intervention part of the study i.
Twenty-six CR and 7 control group participants completed the entire study. The participants who did not complete the CR protocol did not differ from the completers in regards to age, body weight, body fat, CRP, or insulin, but did have lower baseline F 2 -isoprostane plasma concentrations Baseline demographic and anthropometric characteristics are shown in Table 1.
Adherence to the protocol in completers was good as measured by urinary biomarkers calculated as ratios of reported intake and excretion for protein 1.
We fit a linear model of F 2 -isoprostane within the 28 days study period using generalized least squares. F 2 -isoprostane was log transformed since the distribution was skewed. Figure 2 , Table 3. The average caloric intake was significantly lower in the CR than in the control group with an average intake of By the end of the dietary intervention Day 29 , total body weight and body fat weight decreased in the CR more than in the control group difference 2.
However, differences in body weight and body fat between CR and control groups were non-significant at baseline, end of intervention, and day follow-up Table 5. There was no significant between group difference in REE adjusted for fat free mass. The CR diet did not have a significant effect on either systolic or diastolic blood pressure or serum concentrations of insulin, leptin, adiponectin, total cholesterol, LDL cholesterol, HDL cholesterol, CRP and triglycerides Tables 8 and 9.
The novelty of the present study is that we investigated serial changes in a marker of oxidative stress induced by days of a caloric restriction diet. The magnitude of this change was significant in comparison to baseline F 2 -isoprostane plasma concentrations. This suggests that the potential benefits from reducing the oxidative stress level can be achieved rapidly without restricting caloric intake to a level that overweight and obese people might find difficult to sustain.
CR is hypothesized to lessen oxidative damage by reducing energy flux and metabolism with a consequential lowering of reactive oxygen species and rate of oxidative damage to vital tissues [36]. Several studies documented the association of CR with lowering of resting metabolic rate and thermic effect of food, and a decrease in cost of physical activity [37].
In the present study, we did not observe significant reductions in adjusted energy expenditure most likely because of a much shorter intervention period 1 month vs. Other reported benefits of long-term CR, but not detected in our study, include reduction in fasting glucose and insulin, which are linked to decreased insulin resistance and risk for type 2 diabetes [39].
Our results showing decreased F 2 -isoprostane with weight loss are consistent with a previous Davi et al [40] study involving 11 obese women who participated in a diet-induced weight loss program for a week period and lost at least 5 kg of initial body weight.
In eight of these women, there was a significant reduction in urinary excretion of F 2 -isoprostane. In contrast, a randomized controlled trial with 42 participants with the metabolic syndrome assigned to 16 weeks of weight maintenance or a week weight-loss program followed by 4 weeks of weight stabilization, showed different results.
Relative to the weight-maintenance group, a 4-kg loss in weight resulted in a significant decrease in blood pressure but did not alter urinary or plasma F 2 -isoprostane [41]. The discrepancies between these studies could be explained, at least in part, by different methodology plasma or urinary isoprostanes , various experimental designs, and diverse study populations.
Baseline F 2 -isoprostane correlated with body fat content. However, the F 2 -isoprostane decrease during the CR intervention was not correlated with the concurrent changes in body fat.
Although we used a clinical trial design, strict diet control, and validated biomarkers [42] , [43] , it was not possible to determine whether body fat itself was a source of oxidative stress.
As far as we are aware, F 2 -isoprostanes, although present in foods, are not absorbed through the gut [44] , [45]. A plausible explanation is that in addition to a decrease in energy content, changes in content and amount of macronutrients consumed affected systemic oxidative balance. Lower concentrations of protein, carbohydrates, and lipids in the CR diet, when compared to habitual diets reported by Control diet participants, could have potentially shifted postprandial oxidative status towards decreased susceptibility to oxidative damage [46].
Indeed, previous research has shown that postprandial increases of lipid and carbohydrate concentrations lead to increased oxidative stress [47] and consequent hyperlipidemia and hyperglycemia [48]. Although our study did not test whether decreases in oxidative stress are linked to an improvement in risk factors for associated chronic diseases, previous data do provide such evidence.
Zacardi et al [49] reported that declines in adhesion molecules and improvement in endothelial function with sustained weight loss were related to decreases in IL-6 and TNF-α, independent of change in adiposity and body fat distribution. Despite the many studies that have examined the role of oxidative stress on cardiovascular health, mechanistic studies designed to abruptly reduce plasma oxidative stress and to subsequently determine the acute effects of this intervention on antioxidative capacity, oxidative stress, and vascular function have not been extensively reported.
For example, studies in young and older individuals demonstrated a dichotomous effect of antioxidant consumption on endothelial function with age [50]. Nevertheless, if the link between obesity and increased oxidative stress is confirmed, the potential for antioxidant therapy to decrease the risk of obesity-related co-morbid conditions such as cardiovascular disease warrants additional studies in diverse populations [51].
Our findings extend those of previous studies in several ways. First, our data provide evidence from a controlled trial design that the decrease in oxidative stress biomarkers induced by a modest caloric restriction is rapid.
Second, the study causally links the measured decreases in F 2 -isoprostane to the weight loss induced by caloric restriction. Third, we demonstrated that return to a habitual diet, with consequent gradual regaining of weight, causes an increase of F 2 -isoprostane to pre-study, elevated baseline levels.
This observation may have clinical significance especially in weight cycling yo-yo dieting [53] , [54] and weight-loss maintenance [55]. Weight cycling has a negative impact on body composition and body fat distribution [59] , [60] , and has been associated with an increased risk for metabolic syndrome [61] ,cardiovascular disease [62] , and all-cause mortality [63].
Now we have a clear understanding of how weight cycling stimulates adjustments in energy homeostatic hormones leptin, ghrelin, and insulin that activate regulatory mechanisms to restore weight [64]. However, we do not know whether energy intake-induced weight cycling is affecting oxidative stress level.
Our results support the notions that during caloric restriction and subsequent weight loss, oxidative stress level decreases, and in contrast, increases during a positive caloric balance and subsequent weight gain.
Thus, we hypothesize that previously mentioned health consequences of weight cycling such as increased risk for metabolic syndrome and cardiovascular disease could be associated, at least in part, with changes in the oxidative stress level.
Future clinical studies are necessary to explain whether these associations can be attenuated by frequent weight cycling and what mechanisms e. lipids oxidation, insulin resistance, and inflammation are involved. A limitation of the present study is the relatively small number of participants; hence, the results need to be confirmed in larger studies.
In addition, individuals in the control group ate their habitual diets, thus it was possible that their intake of antioxidants e. Although the use of F 2 -isoprostanes as a marker of oxidative stress is a strength [66] , the study would have greatly benefited from measurement of water-soluble oxidation markers such as thiobarbituric acid reactive substances [39] and total antioxidant capacity [67] , [68].
However, in the study on effect of diet-induced reduction in oxidative stress it has been showed that F 2 -isoprostane level was well correlated with advanced oxidation protein products [69].
Further studies will be required to determine whether caloric restriction and weight loss lead to a reduction in F 2 -isoprostane and other markers of oxidative stress in such conditions.
Finally, we did not explore the effect of age on our results. For example, it has been shown that antioxidant consumption acutely restores endothelial function in the elderly while disrupting normal endothelium-dependent vasodilation in the young, and suggest that this age-related impairment is attributed, at least in part, to free radicals [70].
However, participants in our study were relatively healthy premenopausal women eliminating, at least in part, the potential effect of age on the results. Simultaneous reduction in markers of inflammation was associated with decreases in body fat and body weight.
These changes suggest potential health benefits of modest caloric restriction in overweight and obese women. Conceived and designed the experiments: MSB NH LJR.
Performed the experiments: MSB LJR. Analyzed the data: MSB NH JW SA LJR LW. Wrote the paper: MSB JW SA LJR LW. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Article Authors Metrics Comments Media Coverage Reader Comments Figures.
Abstract Objectives It is not established to what extent caloric intake must be reduced to lower oxidative stress in humans. Results Baseline median F 2 -isoprostane concentration Conclusions Oxidative stress can be rapidly reduced and sustained through a modest reduction in caloric intake suggesting potential health benefits in overweight and obese women.
Trial Registration Clinicaltrials. gov NCT Introduction Obesity is associated with increased oxidative stress and chronic low-grade chronic inflammation [1] — [4]. Methods The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1 and Protocol S1.
Download: PPT. The effects of caloric restriction against ethanol-induced oxidative and nitrosative cardiotoxicity and plasma lipids in rats. Vucevic D , Mladenovic D , Ninkovic M , Aleksic V , Stankovic MN , Stankovic M , Jorgacevic B , Vukicevic RJ , Radosavljevic T Exp Biol Med Maywood , 12 , 24 Oct Cited by: 6 articles PMID: Effect of 8.
Gómez J , Caro P , Naudí A , Portero-Otin M , Pamplona R , Barja G Biogerontology , 8 5 , 08 May Cited by: 30 articles PMID: Acar A , Görenek L , Aydin A , Eyigün CP , Eken A , Sayal A , Pahsa A Mikrobiyol Bul , 43 3 , 01 Jul Cited by: 8 articles PMID: Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity.
Calabrese V , Cornelius C , Cuzzocrea S , Iavicoli I , Rizzarelli E , Calabrese EJ Mol Aspects Med , 32 , 01 Aug Cited by: articles PMID: Review. Minireview: the role of oxidative stress in relation to caloric restriction and longevity. Gredilla R , Barja G Endocrinology , 9 , 26 May Cited by: articles PMID: Review.
Claim to ORCID Get citation. Follow us News blog Technical blog Twitter YouTube. About About Europe PMC.
Become a funder. Tools Tools overview. ORCID article claiming. Journal list. Grant finder. External links service. Annotations submission service. Developers Developer resources.
Articles RESTful API. Grants RESTful API. API case studies. SOAP web service. Annotations API. OAI service.
Bulk downloads. Developers Forum. Help Help using Europe PMC. Search syntax reference. Contact us Helpdesk. Tech blog. Developer forum. Let us know how we are doing. How are we doing. Europe PMC is a GBC global core biodata resource.
For more information about PLOS Subject Oxidayive, click here. It is not established to oxidatife extent caloric intake must oxidatife reduced to lower Carbohydrate metabolism and metabolic rate stress in caloric restriction and oxidative stress. The aim of this caloric restriction and oxidative stress was to determine the resfriction of short-term, moderate restruction restriction on markers of restrictiln stress cloric inflammation in overweight and obese premenopausal women. Weight, anthropometry, validated markers of oxidative stress F 2 -isoprostane and inflammation C-reactive proteinadipokines, hormones, lipids, interleukins, and blood pressure were assessed at baseline, during the intervention, and at follow-up. Baseline median F 2 -isoprostane concentration After starting of the caloric restriction diet, F 2 -isoprostane levels fell rapidly in the CR group, reaching statistical difference from the control group by day 5 median Oxidative stress can be rapidly reduced and sustained through a modest reduction in caloric intake suggesting potential health benefits in overweight and obese women.
Ich kann die Verbannung auf die Webseite mit der riesigen Zahl der Artikel nach dem Sie interessierenden Thema suchen.
Mich beunruhigt diese Frage auch.
Ich entschuldige mich, aber es kommt mir nicht heran. Es gibt andere Varianten?