Lifelong soya consumption in males does not increase lifespan but increases health span under a metabolic stress such as type 2 diabetes mellitus.

Soya consumption can decrease oxidative stress in animal models. Moreover, phytoestrogens such as genistein, present in soya, can mimic some of the beneficial effects of estrogens and are devoid of significant side effects, such as cancer. In this study, we have performed a controlled lifelong study with male OF1 mice that consumed either a soya-free diet or a soya-rich diet. We show that, although we found an increase in the expression and activity of antioxidant enzymes in soya-consuming mice, it did not increase lifespan. We reasoned that the soya diet could not increase lifespan in a very healthy population, but perhaps it could extend health span in stressed animals such as type 2 diabetic Goto Kakizaki (GK) rats. Indeed, this was the case: we found that male GK rats consuming a soya-rich diet developed the disease at a lower rate and, therefore, lived longer than soya-free diet-consuming rats.

Acute Increase in Blood αCGRP at Maximal Exercise and Its Association to Cardiorespiratory Fitness, Carbohydrate Oxidation and Work Performed: An Exploratory Study in Young Men.

This study aimed to explore if the acute variations in plasma concentration of α-calcitonin gene-related peptide (αCGRP) induced by a single maximal exercise bout may be associated to cardiorespiratory fitness and carbohydrate oxidation in humans. Twelve young adult Caucasian men (24.3 ± 0.9 years-old; 179.2 ± 1.9 cm of height; 23.9 ± 0.6 kg·m-2 body mass index) performed a graded exercise test. A venous catheter was placed before testing, and blood samples were taken at baseline, maximal effort and recovery. αCGRP was measured in plasma using a commercial double-sandwich enzyme-linked-immunoassay. A two-way repeated measurements ANOVA was used to compare the values obtained at baseline, maximal effort and recovery. In the whole sample, αCGRP increased at maximal effort and its concentration correlated directly, albeit non-significantly, with the muscle mass normalised VO2, VCO2, carbohydrate oxidation and relative power. Two thirds of the participants showed an increase in αCGRP concentration at maximal effort. Post hoc analysis showed that in these individuals, the muscle mass normalised VO2, VCO2, carbohydrate oxidation rate and relative power were higher than in the participants lacking this molecular response. Therefore, our data suggest that (a) a majority of young men respond to exercise with an increase in blood αCGRP concentration; and (b) individuals exhibiting this response also show a higher cardiorespiratory fitness, carbohydrate oxidation and work performed. These findings suggest that this neuropeptide could act as an exerkine with potential effects on physical performance.

Nutritional strategies in an elite wheelchair marathoner at 3900 m altitude: a case report.

BACKGROUND: Altitude training is a common practice among middle-distance and marathon runners. During acclimatization, sympathetic drive may increase resting metabolic rate (RMR), therefore implementation of targeted nutritional interventions based on training demands and environmental conditions becomes paramount. This single case study represents the first nutritional intervention performed under hypobaric hypoxic conditions (3900 m) in Paralympic sport. These results may elucidate the unique nutritional requirements of upper body endurance athletes training at altitude. CASE PRESENTATION: This case study examined the effects of a nutritional intervention on the body mass of a 36-year-old professional wheelchair athlete (silver medalist at the Paralympic Games and 106 victories in assorted road events) during a five-week altitude training camp, divided into pre-altitude at sea level (BN), acclimatization to altitude (Puno, 3860 m) (BH), specific training (W1,2,3,4) and return to sea level (Post) phases. Energy intake (kcal) and body mass (kg) were recorded daily. Results demonstrated significant decrease in body mass between BN and BH (52.6 ± 0.4 vs 50.7 ± 0.5 kg, P < 0.001) which returned to pre-altitude values, upon returning to sea level at Post (52.1 ± 0.5 kg). A greater daily intake was observed during BH (2899 ± 670 kcal) and W1,2,3 (3037 ± 490; 3116 ± 170; 3101 ± 385 kcal) compared to BN (2397 ± 242 kcal, P < 0.01) and Post (2411 ± 137 kcal, P < 0.01). No differences were reported between W4 (2786 ± 375 kcal), BN and Post. The amount of carbohydrates ingested (g · kg- 1) was greater in W1,2,3, (9.6 ± 2.1; 9.9 ± 1.2; 9.6 ± 1.2) than in BN (7.1 ± 1.2) and Post (6.3 ± 0.8, P < 0.001). Effect sizes (Cohen's d) for all variables relative to BN (all time points) exceed a large effect (d > 0.80). CONCLUSIONS: These results suggest an elite wheelchair marathoner training at 3860 m required increased nutrient requirements as well as the systematic control needed to re-adapt a nutritional program. Moreover, our findings highlight training and nutritional prescription optimization of elite wheelchair athletes, under challenging environmental conditions.

Sex Differences in Age-Associated Type 2 Diabetes in Rats-Role of Estrogens and Oxidative Stress.

Females live longer than males, and the estrogens are one of the reasons for this difference. We reported some years ago that estrogens are able to protect rats against oxidative stress, by inducing antioxidant genes. Type 2 diabetes is an age-associated disease in which oxidative stress is involved, and moreover, some studies show that the prevalence is higher in men than in women, and therefore there are sex-associated differences. Thus, the aim of this study was to evaluate the role of estrogens in protecting against oxidative stress in type 2 diabetic males and females. For this purpose, we used Goto-Kakizaki rats, which develop type 2 diabetes with age. We found that female diabetic rats showed lower glycaemia levels with age than did diabetic males and that estrogens enhanced insulin sensitivity in diabetic females. Moreover, glucose uptake, measured by positron emission tomography, was higher in the female brain, cerebellum, and heart than in those from male diabetic rats. There were also sex-associated differences in the plasma metabolic profile as determined by metabolomics. The metabolic profile was similar between estrogen-replaced and control diabetic rats and different from ovariectomized diabetic rats. Oxidative stress is involved in these differences. We showed that hepatic mitochondria from females produced less hydrogen peroxide levels and exhibited lower xanthine oxidase activity. We also found that hepatic mitochondrial glutathione oxidation and lipid oxidation levels were lower in diabetic females when compared with diabetic males. Ovariectomy induced oxidative stress, and estrogen replacement therapy prevented it. These findings provide evidence for estrogen beneficial effects in type 2 diabetes and should be considered when prescribing estrogen replacement therapy to menopausal women.

Influence of Training Models at 3,900-m Altitude on the Physiological Response and Performance of a Professional Wheelchair Athlete: A Case Study.

Sanz-Quinto, S, López-Grueso, R, Brizuela, G, Flatt, AA, and Moya-Ramón, M. Influence of training models at 3,900-m altitude on the physiological response and performance of a professional wheelchair athlete: A case study. J Strength Cond Res 33(6): 1715-1723, 2019-This case study compared the effects of two training camps using flexible planning (FP) vs. inflexible planning (IP) at 3,860-m altitude on physiological and performance responses of an elite marathon wheelchair athlete with Charcot-Marie-Tooth disease (CMT). During IP, the athlete completed preplanned training sessions. During FP, training was adjusted based on vagally mediated heart rate variability (HRV) with specific sessions being performed when a reference HRV value was attained. The camp phases were baseline in normoxia (BN), baseline in hypoxia (BH), specific training weeks 1-4 (W1, W2, W3, W4), and Post-camp (Post). Outcome measures included the root mean square of successive R-R interval differences (rMSSD), resting heart rate (HRrest), oxygen saturation (SO2), diastolic blood pressure and systolic blood pressure, power output and a 3,000-m test. A greater impairment of normalized rMSSD (BN) was shown in IP during BH (57.30 ± 2.38% vs. 72.94 ± 11.59%, p = 0.004), W2 (63.99 ± 10.32% vs. 81.65 ± 8.87%, p = 0.005), and W4 (46.11 ± 8.61% vs. 59.35 ± 6.81%, p = 0.008). At Post, only in FP was rMSSD restored (104.47 ± 35.80%). Relative changes were shown in power output (+3 W in IP vs. +6 W in FP) and 3,000-m test (-7s in IP vs. -16s in FP). This case study demonstrated that FP resulted in less suppression and faster restoration of rMSSD and more positive changes in performance than IP in an elite wheelchair marathoner with CMT.

Monitoring Heart Rate Variability Before and After a Marathon in an Elite Wheelchair Athlete: A Case Study.

The purpose of this study was to analyze heart rate variability (HRV) oscillations before and after a marathon which involved trans-meridian air travel and substantial time zone differences in a professional wheelchair athlete with Charcot-Marie-Tooth (CMT) disease. The natural logarithm of the root mean square difference between adjacent normal R-R intervals (Ln rMSSD) was measured daily on the days before, including and following the race. Relative to baseline, small (-3.8 - -4.6%) reductions in LnRMSSD were observed following relocation and on race-day, indicating only minor effects of travel on cardiac-autonomic activity. On the morning following the marathon, a 23.1% reduction in Ln rMSSD was observed, which returned to baseline by 48 h. The race time set by the athlete was the world-leading time in his class. This case study showed that Ln rMSSD responses to marathon in an elite wheelchair athlete with CMT was similar to those previously reported among unrestricted endurance athletes.

Influence of Training Load on Mood Disturbance at Sea Level and 3900 m Altitude: A Case Study of a Wheelchair Athlete.

The purpose of this case study was to investigate the influence of a training load (TL), oxygen saturation (SO2) and blood pressure (BP) on mood states in a wheelchair marathoner during (7 weeks at sea level (SL), 5 weeks at 3860 m altitude, 1 week returning to SL). TL was obtained with Foster's equation while mood states were obtained with the Profile of Mood States Questionnaire (POMS). Furthermore, SO2 and BP were assessed upon wakening. SO2 (%) decreased at altitude, compared to SL (88.31 ± 2.46 vs. 98.52 ± 0.11) and increased until the last week at altitude (92.64 ± 1.12). Systolic pressure (SP) increased at altitude compared to pre-altitude (126.0 ± 5.1 vs. 107.6 ± 4.4 mmhg), and was not different from the last week at altitude. Controlling for SO2 and SP, differences were also observed in fatigue (97.66 ± 18.92 vs. 17.39 ± 13.71) and vigor (73.23 ± 8.62 vs. 26.48 ± 11.89) as a function of altitude. Upon return to SL, fatigue, vigor, SO2 and SP returned to pre values. This case study demonstrated the POMS was sensitive to worsening patterns in fatigue and vigor at altitude through a practical survey approach combined with daily physiological assessment.

Metabolomic analysis of long-term spontaneous exercise in mice suggests increased lipolysis and altered glucose metabolism when animals are at rest.

Exercise has been associated with several beneficial effects and is one of the major modulators of metabolism. The working muscle produces and releases substances during exercise that mediate the adaptation of the muscle but also improve the metabolic flexibility of the complete organism, leading to adjustable substrate utilization. Metabolomic studies on physical exercise are scarce and most of them have been focused on the effects of intense exercise in professional sportsmen. The aim of our study was to determine plasma metabolomic adaptations in mice after a long-term spontaneous exercise intervention study (18 mo). The metabolic changes induced by long-term spontaneous exercise were sufficient to achieve complete discrimination between groups in the principal component analysis scores plot. We identified plasma indicators of an increase in lipolysis (elevated unsaturated fatty acids and glycerol), a decrease in glucose and insulin plasma levels and in heart glucose consumption (by PET), and altered glucose metabolism (decreased alanine and lactate) in the wheel running group. Collectively these data are compatible with an increase in skeletal muscle insulin sensitivity in the active mice. We also found an increase in amino acids involved in catecholamine synthesis (tyrosine and phenylalanine), in the skeletal muscle pool of creatine phosphate and taurine, and changes in phospholipid metabolism (phosphocholine and choline in lipids) between the sedentary and the active mice. In conclusion, long-term spontaneous wheel running induces significant plasma and tissue (heart) metabolic responses that remain even when the animal is at rest.

Early, but not late onset estrogen replacement therapy prevents oxidative stress and metabolic alterations caused by ovariectomy.

AIMS: The usefulness of estrogen replacement therapy (ERT) in preventing oxidative stress associated with menopause is controversial. We aimed to study if there is a critical time window for effective treatment of the effects of ovariectomy with estrogens at the molecular, metabolic, and cellular level. RESULTS: Our main finding is that early, but not late onset of ERT prevents an ovariectomy-associated increase in mitochondrial hydrogen peroxide levels, oxidative damage to lipids and proteins, and a decrease in glutathione peroxidase and catalase activity in rats. This may be due to a change in the estrogen receptor (ER) expression profile: ovariectomy increases the ER α/ß ratio and immediate estrogen replacement prevents it. Positron emission tomography analysis shows that ovariectomy decreases the brain glucose uptake in vivo and that estrogen administration is beneficial, but only if administered immediately after deprivation. Ovariectomy decreases GLUT-1 and 3 glucose transporters in the brain, and only early onset estrogen administration prevents it. Plasma from rats treated with estrogens immediately after ovariectomy show similar metabolomics profiles as controls. INNOVATION: We provide molecular basis for the recommendation of early onset ERT and explain its lack of effectiveness if a significant time period elapses after ovariectomy and probably after the onset of menopause. CONCLUSION: Only early, but not late onset administration of estrogens after ovariectomy has beneficial effects at molecular levels on oxidative stress, brain glucose uptake, and metabolomic profiles.

Resveratrol: distribución, propiedades y perspectivas / Resveratrol: distribution, properties and perspectives

El resveratrol es un polifenol natural presente en numerosas plantas y frutos como cacahuetes, moras, arándanos y, sobre todo, en la uva y el vino tinto. Su síntesis está condicionada por la presencia de factores estresantes, tales como la contaminación fúngica o la radiación ultravioleta. En las plantas actúa como fitoalexina, es decir, posee la capacidad de inhibir el progreso de ciertas infecciones. La medicina antigua ha utilizado extractos de plantas que contienen resveratrol desde hace más de 2.000 años y hace más de 30 años que se aisló y se comenzaron a estudiar sus propiedades con métodos científicos. Sus propiedades in vitro han sido ampliamente estudiadas y contrastadas, entre ellas cabe destacar su actividad como anticancerígeno, antiagregante plaquetario, antiinflamatorio, antialérgico, etc. En cuanto a sus propiedades in vivo su actividad no está tan clara; existen numerosos estudios que encuentran beneficios sobre el sistema cardiovascular, enfermedades como la diabetes y sobre la longevidad; sin embargo, otros autores no encuentran una equivalencia de los estudios in vitro a in vivo. Esta discrepancia es debida a la biodisponibilidad que tiene el resveratrol. Tras un consumo oral se ha comprobado que la absorción es muy buena, pero las vías metabólicas dejan solo una pequeña fracción de resveratrol libre en sangre, por lo que la disponibilidad en los tejidos diana es muy baja y no se llegan a las concentraciones empleadas en los estudios in vitro. Así pues, aunque los estudios in vitro indican que se trata de una molécula biológicamente activa con propiedades saludables, los estudios realizados in vivo hasta el momento no pueden confirmar parte de estos resultados, lo cual puede atribuirse a su baja biodisponibilidad(AU)

Resveratrol is a natural polyphenol which can be found in many plants and fruits, such as peanuts, mulberries, blueberries and, above all, in grapes and red wine. Its synthesis is regulated by the presence of stressful factors, such as fungal contamination and ultra-violet radiation. In plants, it plays a role as a phytoalexin, showing a capacity to inhibit the development of certain infections. Plant extracts which contain resveratrol have been employed by traditional medicine for more than 2000 years. Resveratrol was first isolated, and its properties were initially studied with scientific methods, thirty years ago. Its in vitro properties have been extensively studied and demonstrated. It is worth highlighting its activity as an anti-cancer agent, platelet anti-aggregation agent, anti-inflammatory, antiallergenic, etc. The activity of its in vivo properties are not so clear. There are many studies that report benefits on the cardiovascular system, illnesses such as diabetes, and in longevity. However, other authors did not find any agreement between in vitro and in vivo studies. This discrepancy is due to the bioavailability of resveratrol. After an oral dose, it has been demonstrated that the absorption is very high, but the metabolic pathways leave just a little free resveratrol in blood, therefore the bioavailability in the target tissues is very low and the concentrations used in in vitro studies are not found in these tissues. Thus, resveratrol is a very active molecule for maintaining health, but due to the low bioavailability not all the in vitro effects can be translated to in vivo. This opens a new potential approach, seeking derivatives of resveratrol that can be measured in the desired tissues(AU)

[Resveratrol: distribution, properties and perspectives]. / Resveratrol: distribución, propiedades y perspectivas.

Resveratrol is a natural polyphenol which can be found in many plants and fruits, such as peanuts, mulberries, blueberries and, above all, in grapes and red wine. Its synthesis is regulated by the presence of stressful factors, such as fungal contamination and ultra-violet radiation. In plants, it plays a role as a phytoalexin, showing a capacity to inhibit the development of certain infections. Plant extracts which contain resveratrol have been employed by traditional medicine for more than 2000 years. Resveratrol was first isolated, and its properties were initially studied with scientific methods, thirty years ago. Its in vitro properties have been extensively studied and demonstrated. It is worth highlighting its activity as an anti-cancer agent, platelet anti-aggregation agent, anti-inflammatory, antiallergenic, etc. The activity of its in vivo properties are not so clear. There are many studies that report benefits on the cardiovascular system, illnesses such as diabetes, and in longevity. However, other authors did not find any agreement between in vitro and in vivo studies. This discrepancy is due to the bioavailability of resveratrol. After an oral dose, it has been demonstrated that the absorption is very high, but the metabolic pathways leave just a little free resveratrol in blood, therefore the bioavailability in the target tissues is very low and the concentrations used in in vitro studies are not found in these tissues. Thus, resveratrol is a very active molecule for maintaining health, but due to the low bioavailability not all the in vitro effects can be translated to in vivo. This opens a new potential approach, seeking derivatives of resveratrol that can be measured in the desired tissues.

Females live longer than males: role of oxidative stress.

One of the most significant achievements of the twentieth century is the increase in human lifespan. In any period studied, females live longer than males. We showed that mitochondrial oxidative stress is higher in males than females and that the higher levels of estrogens in females protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. The chemical structure of estradiol confers antioxidant properties to the molecule. However, the low concentration of estrogens in females makes it unlikely that they exhibit significant antioxidant capacity in the organism. Therefore we studied the mechanisms enabling estradiol to be antioxidant at physiological levels. Our results show that physiological concentrations of estrogens activate estrogen receptors and the MAPK and NFKB pathway. Activation of NFkB by estrogens subsequently activates the expression of Mn-SOD and GPx. Moreover, we have demonstrated that genistein, the most abundant phytoestrogen in soya, reproduces the antioxidant effect of estradiol at nutritionally relevant concentrations by the same mechanism, both in healthy ageing and in Alzheimer's disease. We conclude that estrogens and phytoestrogens up-regulate expression of antioxidant enzymes via the estrogen receptor and MAPK activation, which in turn activate the NFkB signalling pathway, resulting in the up-regulation of the expression of longevity-related genes.

Free [NADH]/[NAD(+)] regulates sirtuin expression.

Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD(+)] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates.

RasGrf1 deficiency delays aging in mice.

RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging, lifespan and metabolic parameters were analyzed in aged RasGrf1(-/-) mice. We observed that mice deficient for RasGrf1(-/-) display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals. Aged RasGrf1(-/-) displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1(-/-). IGF-I levels were lower in RasGrf1(-/-) than in controls. Furthermore, SIRT1 expression was increased in RasGrf1(-/-) animals. Consistent with this, the blood metabolomic profiles of RasGrf1-deficient mice resembled those observed in calorie-restricted animals. In addition, cardiac glucose consumption as determined PET was not altered by aging in the mutant model, indicating that RasGrf1-deficient mice display delayed aging. Our observations link Ras signaling to lifespan and suggest that RasGrf1 is an evolutionary conserved gene which could be targeted for the development of therapies to delay age-related processes.

El envejecimiento y la ovariectomía causan una disminución del consumo cerebral de glucosa in vivo en ratas Wistar / Aging and ovariectomy cause a decrease in brain glucose consumption in vivo in Wistar rats

IntroducciónLa esperanza de vida de la población ha ido incrementándose en el siglo xx en ambos sexos. La supervivencia de las mujeres ha sido siempre mayor respecto a los hombres, aunque estas diferencias de longevidad se reproducen en otras especies animales, como las ratas. Debe existir alguna base biológica que sustente dichas diferencias entre sexos, las cuales pueden ser explicadas por la acción de los estrógenos, ya que la ovariectomía (OVX) anula las ventajas en el sexo femenino asemejándolo al masculino.ObjetivosNuestros objetivos fueron estudiar el consumo cerebral de glucosa in vivo en ratas hembras Wistar jóvenes y viejas (V), además de evaluar el efecto de la OVX sobre dicha captación cerebral de glucosa.Material y métodosUsamos ratas hembras Wistar, divididas en grupos jóvenes (4–7 meses), jóvenes Control (Sham), ovariectomizadas (3 y 6 semanas) y V (22–24 meses). Tras la administración intravenosa de 18F-fluordeoxiglucosa se midió la captación de glucosa cerebral in vivo mediante tomografía por emisión de positrones.ResultadosSe produjo una disminución significativa en el consumo cerebral de glucosa en las ratas V respecto a las jóvenes. Resultados similares hallamos en la captación de glucosa entre las ratas Control y ovariectomizadas de 3 y de 6 semanas.ConclusionesEl envejecimiento produce una disminución en el metabolismo cerebral de glucosa. La OVX reduce el consumo cerebral de glucosa significativamente respecto a las ratas Control de manera similar al envejecimiento(AU)

IntroductionThe life expectancy of the population has been increased steadily over the twentieth century in both genders. The survival of women has always been higher compared to men and these differences in longevity are reproduced in other animal species such as rats.IntroductionThere must be some biological basis to support the differences in longevity between males and females. Differences can be explained by the effects of estrogens because ovariectomy cancels out the benefits shown in females compared to males.AimOur aims were to study the cerebral glucose consumption in vivo in young and old female Wistar rats and evaluate the effect of ovariectomy on the brain glucose uptake.Material and methodsWe used female Wistar rats, divided into young (4–7 months), young control (Sham) and ovariectomized (3 or 6 weeks) and old (22–24 months) groups. After intravenous administration of 18F-fluorodeoxyglucose (FDG) the cerebral glucose uptake was measured in vivo by Positron Emission Tomography (PET).ResultsThere was a significant decrease in cerebral glucose consumption in old rats compared with young rats. Similar results were found in glucose uptake when comparing control rats with ovariectomized rats, i.e., ovariectomy significantly reduces the brain glucose consumption.ConclusionsAging causes a decrease in cerebral glucose metabolism. Ovariectomy reduces cerebral glucose consumption significantly compared to control rats and is similar to the old group(AU)

[Aging and ovariectomy cause a decrease in brain glucose consumption in vivo in Wistar rats]. / El envejecimiento y la ovariectomía causan una disminución del consumo cerebral de glucosa in vivo en ratas Wistar.

INTRODUCTION: The life expectancy of the population has been increased steadily over the twentieth century in both genders. The survival of women has always been higher compared to men and these differences in longevity are reproduced in other animal species such as rats. There must be some biological basis to support the differences in longevity between males and females. Differences can be explained by the effects of estrogens because ovariectomy cancels out the benefits shown in females compared to males. AIM: Our aims were to study the cerebral glucose consumption in vivo in young and old female Wistar rats and evaluate the effect of ovariectomy on the brain glucose uptake. MATERIAL AND METHODS: We used female Wistar rats, divided into young (4-7 months), young control (Sham) and ovariectomized (3 or 6 weeks) and old (22-24 months) groups. After intravenous administration of 18F-fluorodeoxyglucose (FDG) the cerebral glucose uptake was measured in vivo by Positron Emission Tomography (PET). RESULTS: There was a significant decrease in cerebral glucose consumption in old rats compared with young rats. Similar results were found in glucose uptake when comparing control rats with ovariectomized rats, i.e., ovariectomy significantly reduces the brain glucose consumption. CONCLUSIONS: Aging causes a decrease in cerebral glucose metabolism. Ovariectomy reduces cerebral glucose consumption significantly compared to control rats and is similar to the old group.

Direct antioxidant and protective effect of estradiol on isolated mitochondria.

Estrogens have antioxidant properties which are due to their ability to bind to estrogen receptors and to up-regulate the expression of antioxidant enzymes via intracellular signalling pathways. Mitochondria are key organelles in the development of age-associated cellular damage. Recently, estrogen receptors were identified in mitochondria. The aim of this paper was to test whether estradiol directly affects mitochondria by preventing oxidative stress and protecting frail mitochondria. Incubation with estradiol at normal intracellular concentrations prevents the formation of reactive oxygen species by mitochondria in a saturable manner. Moreover, estradiol protects mitochondrial integrity as indicated by an increase in mitochondrial membrane potential. It also prevents the apoptogenic leakage of cytochrome c from mitochondria and as a result the mitochondrial content of this cytochrome c is maintained high. Thus, estradiol prevents the onset of the mitochondrial pathway of apoptosis by a direct effect on the organelle. Genistein, a phytoestrogen present at high concentration in soy, mimics the protective effect of estradiol by both decreasing the rate of formation of reactive oxygen species and preventing the release of cytochrome c from mitochondria.

Low in vivo brain glucose consumption and high oxidative stress in accelerated aging.

The validity of the free radical theory of aging has been recently questioned. Our aim was to test whether there is oxidative stress in tissues critically involved in accelerated aging (senescence-accelerated mice, SAM) and whether this correlates with lower glucose consumption in vivo and behavioural tests. Positron emission tomography shows that brains of old SAM-prone animals consume less glucose than young ones. Behavioural characteristics, mitochondrial peroxide production, and damage in both the central nervous system and bone marrow stem cells also indicate that SAM-prone animals age faster than SAM-resistant ones. Our results support the role of the free radical theory of aging in critical tissues involved in aging and that this correlates with glucose consumption.