Vitamin C supplementation decreases training efficiency because it prevents some cellular adaptations to exercise.

Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol.

Reactive oxygen or nitrogen species (RONS) are produced during exercise due, at least in part, to the activation of xanthine oxidase. When exercise is exhaustive they cause tissue damage; however, they may also act as signals inducing specific cellular adaptations to exercise. We have tested this hypothesis by studying the effects of allopurinol-induced inhibition of RONS production on cell signalling pathways in rats submitted to exhaustive exercise. Exercise caused an activation of mitogen-activated protein kinases (MAPKs: p38, ERK 1 and ERK 2), which in turn activated nuclear factor κB (NF-κB) in rat gastrocnemius muscle. This up-regulated the expression of important enzymes associated with cell defence (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when RONS production was prevented by allopurinol. Thus we report, for the first time, evidence that decreasing RONS formation prevents activation of important signalling pathways, predominantly the MAPK-NF-κB pathway; consequently the practice of taking antioxidants before exercise may have to be re-evaluated.

No abstract

The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.

Telomerase confers limitless proliferative potential to most human cells through its ability to elongate telomeres, the natural ends of chromosomes, which otherwise would undergo progressive attrition and eventually compromise cell viability. However, the role of telomerase in organismal aging has remained unaddressed, in part because of the cancer-promoting activity of telomerase. To circumvent this problem, we have constitutively expressed telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice engineered to be cancer resistant by means of enhanced expression of the tumor suppressors p53, p16, and p19ARF. In this context, TERT overexpression improves the fitness of epithelial barriers, particularly the skin and the intestine, and produces a systemic delay in aging accompanied by extension of the median life span. These results demonstrate that constitutive expression of Tert provides antiaging activity in the context of a mammalian organism.

Summary

We have studied the possible correlation between nuclear glutathione distribution and the progression of the cell cycle. The former was studied by confocal microscopy using 5-chloromethyl fluorescein diacetate and the latter by flow cytometry and protein expression of Id2 and p107. In proliferating cells, when 41% of them were in the S؉G 2 /M phase of the cell cycle GSH was located mainly in the nucleus. When cells reached confluence (G 0 /G 1 ) GSH was localized in the cytoplasm with a perinuclear distribution. The nucleus/cytoplasm fluorescence ratio for GSH reached a maximal mean value of 4.2 ؎ 0.8 at 6 h after cell plating. A ratio higher than 2 was maintained during exponential cell growth. In the G 0 /G 1 phase of the cell cycle, the nucleus/cytoplasm GSH ratio decreased to values close to 1. We report here that cells concentrate GSH in the nucleus in the early phases of cell growth, when most of the cells are in an active division phase, and that GSH redistributes uniformly between the nucleus and the cytoplasm when cells reach confluence.Glutathione (GSH) is the most abundant non-protein thiol in mammalian cells and performs many physiological functions (1). We have reported that cellular glutathione decreases in apoptosis (2).Although the role of nuclear GSH in the synthesis of DNA (3) and in protection against oxidative damage or ionizing radiation (4) is well established, little is known about the concentration of GSH in the nucleus and its regulation. This is due to two main factors. The first is methodological: it is impossible to determine the nuclear concentration of GSH using standard cell fractionation and analytical approaches (for a review see Söderdahl et al. (5). In view of this problem, we used confocal microscopy.The second factor is that most, if not all, of the reports share the common view of nuclear GSH distribution in a static situation. Cells are usually studied under steady state conditions i.e. when they are confluent (G 0 /G 1 phase of the cell cycle). The nucleus changes dramatically during the different phases of the cell cycle. Thus, studies addressed to determining the nuclear GSH distribution must take cell cycle physiology into account. To our knowledge there is a lack of information about the cellular distribution of glutathione during the different phases of the cell cycle and the possible correlation between cellular growth and nuclear GSH levels. We report here that GSH concentrates in the nucleus in the early phases of cell growth, when most of the cells are in an active division phase, and it redistributes uniformly between nucleus and cytoplasm when cells reach confluence. Nuclear Bcl-2 may be responsible for this change, as its expression changes in parallel with glutathione levels in nuclei. EXPERIMENTAL PROCEDURES Cell Culture3T3 fibroblasts were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum and antibiotics (25 units/ml penicillin, 25 g/ml streptomycin, and 0.3 g/ml amphotericin B) in 5% CO 2 in air at 37°C in 25 or 75 cm 2 f...