Physical exercise increases the cellular production of reactive oxygen species (ROS) in muscle, liver, and other organs. This is unlikely due to increased mitochondrial production but rather to ...extramitochondrial sources such as NADPH oxidase or xanthine oxidase. We have reported a xanthine oxidase-mediated increase in ROS production in many experimental models from isolated cells to humans. Originally, ROS were considered as detrimental and thus as a likely cause of cell damage associated with exhaustion. In the past decade, evidence showing that ROS act as signals has been gathered and thus the idea that antioxidant supplementation in exercise is always recommendable has proved incorrect. In fact, we proposed that exercise itself can be considered as an antioxidant because training increases the expression of classical antioxidant enzymes such as superoxide dismutase and glutathione peroxidase and, in general, lowering the endogenous antioxidant enzymes by administration of antioxidant supplements may not be a good strategy when training. Antioxidant enzymes are not the only ones to be activated by training. Mitochondriogenesis is an important process activated in exercise. Many redox-sensitive enzymes are involved in this process. Important signaling molecules like MAP kinases, NF-κB, PGC-1α, p53, heat shock factor, and others modulate muscle adaptation to exercise. Interventions aimed at modifying the production of ROS in exercise must be performed with care as they may be detrimental in that they may lower useful adaptations to exercise.
Bcl-xL as a Modulator of Senescence and Aging Mas-Bargues, Cristina; Borrás, Consuelo; Viña, Jose
International journal of molecular sciences,
02/2021, Letnik:
22, Številka:
4
Journal Article
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Many features of aging result from the incapacity of cells to adapt to stress conditions. When cells are overwhelmed by stress, they can undergo senescence to avoid unrestricted growth of damaged ...cells. Recent findings have proven that cellular senescence is more than that. A specific grade of senescence promotes embryo development, tissue remodeling and wound healing. However, constant stresses and a weakening immune system can lead to senescence chronicity with aging. The accumulation of senescent cells is directly related to tissue dysfunction and age-related pathologies. Centenarians, the most aged individuals, should accumulate senescent cells and suffer from their deleterious effects, however, they enjoy a compression of morbidity. We have shown that they overexpress B-cell lymphoma-extra large (Bcl-xL). Bcl-xL could avoid an excessive burden of senescent cells through the regulation of intrinsic apoptosis, mitochondrial bioenergetics and oxidative stress. On the other hand, Bcl-xL maintains a fully functional immune system that ensures an efficient clearance of senescent cells. Moreover, there is a paradox, as inhibitors of Bcl-xL have been employed as senolytic agents, which have been shown to protect from aging in animal models. In this review, we aim to discuss how Bcl-xL could modulate senescence-associated harmful effects in centenarians, protecting them from the burden of accumulation of senescent cells.
The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the ...theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology.
Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise.
A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity.
Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding.
The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates important processes in cells, such as the cell cycle, by targeting a set of substrates for degradation. In the last ...decade, APC/C has been related to several major functions in the nervous system, including axon guidance, synaptic plasticity, neurogenesis, and neuronal survival. Interestingly, some of the identified APC/C substrates have been related to neurodegenerative diseases. There is an accumulation of some degradation targets of APC/C in Alzheimer's disease (AD) brains, which suggests a dysregulation of the protein complex in the disorder. Moreover, recently evidence has been provided for an inactivation of APC/C in AD. It has been shown that oligomers of the AD-related peptide, Aβ, induce degradation of the APC/C activator subunit cdh1, in vitro in neurons in culture and in vivo in the mouse hippocampus. Furthermore, in the AD mouse model APP/PS1, lower cdh1 levels were observed in pyramidal neurons in CA1 when compared to age-matched wildtype mice. In this review, we provide a complete list of APC/C substrates that are involved in the nervous system and we discuss their functions. We also summarize recent studies that show neurobiological effects in cdh1 knockout mouse models. Finally, we discuss the role of APC/C in the pathophysiology of AD.
The free radical theory of ageing has provided a framework of research into ageing based on Harman's idea that ageing was caused by damage produced by free radicals. However, several experiments have ...cast doubts on the general validity of the theory. The postulation of the free radical theory of frailty came from two basic facts: first that radicals not only act as damaging molecules, but also as signals to control cell function and second that on many occasions oxidative damage does not correlate with chronological but rather with unsuccessful ageing. Frailty is a geriatric concept by which an older person shows a lack of the feeling of wellbeing, unintentional weight loss, a relatively low grip strength, lowering the speed of walking, and difficulties to stand. If left untreated, frailty progresses to disability. Many interventions that prevent oxidative damage to cells do not affect longevity but have a clear effect on the prevention of frailty and its transition to disability. Clinical trials have shown that exercise programmes do not promote longevity but delay the onset of frailty. Experiments and mechanisms to support this idea are described.
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•Chronological aging is not always associated with oxidative damage.•Frailty is a geriatric syndrome by which an older person displays increased vulnerability to minor stresses.•Frailty increases the risk of disability and eventually death.•The free radical theory of frailty proposes that oxidative damage is not associated with aging but with frailty.•This theory provides a rationale to prevent or delay frailty by interventions aiming to protect against oxidative damage.
Antioxidant supplements in exercise: worse than useless? Gomez-Cabrera, Mari Carmen; Ristow, Michael; Viña, Jose
American journal of physiology: endocrinology and metabolism,
2012-Feb-15, Letnik:
302, Številka:
4
Journal Article
The key hallmark of stem cells is their ability to self-renew while keeping a differentiation potential. Intrinsic and extrinsic cell factors may contribute to a decline in these stem cell ...properties, and this is of the most importance when culturing them. One of these factors is oxygen concentration, which has been closely linked to the maintenance of stemness. The widely used environmental 21% O₂ concentration represents a hyperoxic non-physiological condition, which can impair stem cell behaviour by many mechanisms. The goal of this review is to understand these mechanisms underlying the oxygen signalling pathways and their negatively-associated consequences. This may provide a rationale for culturing stem cells under physiological oxygen concentration for stem cell therapy success, in the field of tissue engineering and regenerative medicine.
Purpose
To evaluate the effect of incision design in implant surgery on interproximal bone loss of posterior teeth adjacent to interdental single implants, comparing intrasulcular and paramarginal ...incision. A further aim was to assess the influence of the incision technique on peri‐implant bone remodeling.
Materials and methods
A controlled randomized clinical trial was carried out in a University Clinic. All the patients received an interdental posterior single implant. The incision type was randomly divided into two groups: (a) intrasulcular or (b) paramarginal. Standardized periapical digital radiographs were made with the parallel technique and a silicone index individualized in each patient. Radiographs were made immediately after implant placement, at abutment connection, 6 and 12 months post‐loading. Two radiographic reference points were detected at the interproximal aspect of the adjacent teeth: (A) the cementoenamel junction and (B) the most coronal aspect of the bone crest. The interproximal bone loss of the adjacent teeth was calculated as the difference from A to B between the different follow‐up periods and baseline. Two different examiners evaluated the radiographic measurements twice.
Results
Sixty patients, each with one implant, were included, 30 in each group. A mean interproximal bone loss in teeth of 0.09 mm in the intrasulcular and 0.10 mm in the paramarginal group was found at 12 months post‐loading. Mean peri‐implant bone remodeling was 0.17 mm in the intrasulcular group and 0.15 mm in the paramarginal group. Differences between incision types were not statistically significant (p > .05).
Conclusions
Both incision designs used to place interdental single implants resulted in minimum bone loss at the interproximal aspect of adjacent teeth. The incision design did not significantly influence the radiographically assessed interproximal bone loss nor peri‐implant bone remodeling.
The main risk factors for developing Alzheimer's disease (AD) are age and gender. The incidence of the disease is higher in women than in men, and this cannot simply be attributed to the higher ...longevity of women versus men. Thus, there must be a specific pathogenic mechanism to explain the higher incidence of AD cases in women. In this regard, it is notable that mitochondria from young females are protected against amyloid-beta toxicity, generate less reactive oxygen species, and release less apoptogenic signals than those from males. However, all this advantage is lost in mitochondria from old females. Since estrogenic compounds protect against mitochondrial toxicity of amyloid-beta, estrogenic action may be important in protecting cells from amyloid-beta toxicity and suggests a possible treatment or prevention strategy for AD. Unfortunately, to date, clinical trials with Ginkgo biloba and other estrogenic therapies have not proved successful in treating AD. 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.
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