Jose Vina

..Our general conclusion is that exercise is so effective that it should be considered as a drug, but that more attention should be paid to the dosing and to individual variations between patients...

..These findings also suggest that mitochondria play a minor role as a source of free radicals during exhaustive physical exercise...

..Study of gender differences in longevity may help us to understand the basic processes of aging and to devise practical strategies to increase the longevity of both females and males...

..Phytoestrogens or other selective estrogen receptor modulators lower age-related diseases and prolong life span, at least in experimental animals. This provides rational bases to study their action in humans further...

..The relevance of these findings is discussed in the context with observations made in transgenic animals overexpressing MnSOD or catalase...

..Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed...

..In this chapter we consider the interrelationship between mitochondrial biogenesis stimulated by exercise and the possible impairment of this pathway in ageing leading to mitochondrial deficiency and eventually muscle sarcopenia...

..It was further developed by one of us (JM) in what has become known as the mitochondrial theory of ageing. These theories provide new experimental approaches to further develop our understanding of the phenomenon of ageing...

..Experiments reported here indicate that phytoestrogens might have a role in the prevention of Alzheimer's disease...

..These ideas open up the possibility of using phytoestrogens to prevent the onset of Alzheimer's disease. More studies are required to determine whether estrogens and/or phytoestrogens fulfill these expectations...

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..The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge...

..Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of upregulating antioxidant genes, by hormonal and dietary manipulations, in order to increase longevity is discussed...

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..Thus, the issue of whether antioxidant treatment is of use in AD is not settled and more research is warranted to clarify this point...

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..Knowledge of the mechanism of free-radical formation in exercise is important because it will be useful to prevent oxidative stress and damage associated with exhaustive physical activity...

..The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge...

..The facts reported here provide molecular evidence to explain the different life span in males and females...

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..There is, however, considerable debate regarding the beneficial health effects of vitamin C supplementation...

..Assays performed included: blood gases; reduced glutathione (GSH) and oxidized glutathione (GSSG) in whole blood; glutathione-related enzyme activities; and superoxide dismutase activity (SOD) in erythrocytes...

..Gender and age-related differences seen in the development of AD can also be partially explained...

..These results may have clinical significance in the prevention of late-onset vascular complications of diabetes...

..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...

..Thus upregulation of RCAN1 may be a valuable biomarker for AD risk...

..The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate...

..Therefore, supplementation of AD patients with vitamin E cannot be recommended without determination of its antioxidant effect in each patient...

..These antioxidants may also delay the physiological impairment associated with aging...

..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...

..Adaptation of muscle to increased oxidative stress and the potential mechanisms involved will be highlighted. The role of redox-controlled cell signaling in skeletal muscle health and function is also described...

..Thus, some of the anti-inflammatory effects of estrogenic compounds may be mediated and activated by PPARs suppressing a diverse array of inflammatory responses caused by A beta in astrocytes in primary culture...

..We have found that interfering with free radical metabolism with antioxidants may hamper useful adaptations to training...

..Our molecular studies may provide a basis to determine the effects of genistein and other soy protein-derived products on longevity in both animals and the human population...

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..In conclusion, the lack of gamma-cystathionase activity in over 50% of old lenses is due to decreased gene expression and proteolytic degradation of the oxidized enzyme. This results in a high risk for the development of senile cataract...

..This mechanism would abrogate a rapid recovery of glutathione levels...

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..Oxidative stress generated during apoptosis by mitochondria is not only due to the respiratory chain...

..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...

..Glutathionylation and oxidation of nuclear proteins appear as a reversible physiological mechanism able to regulate DNA compaction, cell cycle and DNA repair...

..when the reduced/oxidized glutathione ratio is high. Consequently glutathione concentration parallels telomerase activity. These results underscore the main role of glutathione in the control of telomerase activity and of the cell cycle...

..The overproduction of ROS by mitochondria, driven by acetaldehyde metabolism, is a common trigger of both mechanisms...

..Differences can be explained by the effects of estrogens because ovariectomy cancels out the benefits shown in females compared to males...

..These results give a possible explanation for this correlation and underscore the role of xanthine oxidase in ageing...

..Moreover, an increased antioxidant enzyme activity, which reflects an oxidative stress, indicates that the antioxidant capacity of the newly born infant may have been surpassed...

..Moreover, any significant improvement in the loss of muscle function will be a major breakthrough in the health and welfare of the population...

..The information provided in the present review suggests an important role of nuclear glutathione as a key regulator of epigenetic events that may be critical in the regulation of cell proliferation...

..On the contrary, high-intensity activation of p53 will result in an increase of oxidative stress by activation of p53-mediated pro-oxidant targets, thus increasing the rate of ageing, but protecting against cancer...

..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...

..As such, more experiments and clinical trials are indeed warranted to find conditions in which estrogenic compounds may be useful to prevent or treat AD...

..The promotion of mitochondriogenesis is critical to prevent aging. In skeletal muscle it has relevance to prevent sarcopenia and frailty...

..In conclusion, the lack of stimulation of mitochondrial biogenesis leads to mtDNA severe depletion and deletions in long-term cholestasis. Hence, long-term cholestasis should be considered a secondary mitochondrial hepatopathy...

..However, we found an increase in plasma protein oxidation in both hypoxic groups. Vitamin C does not affect erythropoiesis and protein oxidation in rats submitted to intermittent hypoxic exposure...

..Our findings suggest that 3 weeks of rHuEpo treatment, which generates an increase of oxygen carrying capacity, can affect mitochondrial biogenesis in a muscle fibre-specific dependent manner...

..Pure oxygen causes more oxidative stress than room air in resuscitation of asphyctic neonates, and consequently could be associated with increased tissue damage...

..Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD...

..Our results may suggest a control role for Id2 in hepatocyte priming, through a p130 dissociation-independent regulation of c-myc...

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..However, contrary to our starting hypothesis, the combination of normobaric hypoxia and sprint training did not improve MAV in our animals...

..We suggest that the small non-coding RNAs signature in centenarians may provide insights into the underlying molecular mechanisms endowing centenarians with extreme longevity...

..This model is mainly based on the cerebral deposition of amyloid β plaques...

..As such, further research is needed before IHH can be widely advocated in myocardial infarction prevention and recovery...

..Finally, molecular biologists have found new age-associated genes by showing changes in longevity of genetically manipulated mice...