Search results for "Free-radical"
showing 10 items of 51 documents
The free radical theory of frailty: Mechanisms and opportunities for interventions to promote successful aging
2019
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 lo…
Exceptional human longevity is associated with a specific plasma phenotype of ether lipids
2019
A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen because of their antioxidant properties and ability to modulate oxidative stress. Our results demonstrate that a specific ether lipid signature can be obtained to define the centenarian state. This profile comprises higher level of alkyl forms derived from phosphatidylcholine with shorter number of carbon atoms and double bonds; and decreased content…
A free radical theory of frailty.
2018
The free radical theory of ageing provided an intellectual framework for many laboratories working on ageing. However, experimental and clinical evidence showing that high doses of antioxidants do not have an effect on ageing or on age-associated diseases, cast doubts on the validity of this theory. Data from our own laboratory show that oxidative damage does not correlate with age, especially in the geriatric population, but rather with the frailty state. This has led us to postulate the free radical theory of frailty that proposes that oxidative damage is associated with frailty, but not with chronological age itself. Superoxide dismutase deficient mice are more frail than controls. But m…
FREE RADICAL THEORY OF FRAILTY: MOLECULAR MECHANISMS OF FRAILTY RESULTING FROM OXIDATIVE STRESS
2018
The free radical theory of ageing provided an intellectual framework for many laboratories working on ageing. However, experimental and clinical evidence showing that high doses of antioxidants did not have an effect on ageing or on age-associated diseases, cast doubts on the validity of this theory. Data from our own laboratory showed that oxidative stress does not correlate with age, especially in the geriatric population, but rather with the frailty state. This has led us to postulate the free radical theory of frailty in which frailty is associated with oxidative stress, but age itself is not. Superoxide dismutase deficient mice are more frail than controls. But more importantly, we obs…
Mitochondrial oxidative stress plays a key role in aging and apoptosis
2000
Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitoch…
Mitochondria, oxidative stress and aging
2000
In the eighties, Miquel and Fleming suggested that mitochondria play a key role in cellular aging. Mitochondria, and specially mitochondrial DNA (mtDNA), are major targets of free radical attack. At present, it is well established that mitochondrial deficits accumulate upon aging due to oxidative damage. Thus, oxidative lesions to mtDNA accumulate with age in human and rodent tissues. Furthermore, levels of oxidative damage to mtDNA are several times higher than those of nuclear DNA. Mitochondrial size increases whereas mitochondrial membrane potential decreases with age in brain and liver. Recently, we have shown that treatment with certain antioxidants, such as sulphur-containing antioxid…
Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment
2009
Alzheimer's disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem …
Glutathione, oxidative stress and aging
1996
The free radical theory of aging proposes that the impairment in physiological performance associated with aging is caused by the detrimental effects of oxygen free radicals. This is interesting because it provides us with a theoretical framework to understand aging and because it suggests a rationale for intervention, i.e., antioxidant administration. Thus, the study of antioxidant systems of the cell may be very important in gerontological studies. Glutathione is one of the main nonprotein antioxidants in the cell which, together with its related enzymes, constitute the “glutathione system.” The involvement of glutathione in aging has been known since the early seventies. Several studies …
Free radical biology of the cardiovascular system
2012
Most cardiovascular diseases (CVDs), as well as age-related cardiovascular alterations, are accompanied by increases in oxidative stress, usually due to increased generation and/or decreased metabolism of ROS (reactive oxygen species; for example superoxide radicals) and RNS (reactive nitrogen species; for example peroxynitrite). The superoxide anion is generated by several enzymatic reactions, including a variety of NADPH oxidases and uncoupled eNOS (endothelial NO synthase). To relieve the burden caused by this generation of free radicals, which also occurs as part of normal physiological processes, such as mitochondrial respiratory chain activity, mammalian systems have developed endogen…
Photochemistry of 7-acetoxybenzopyran derivatives. Synthesis of eupatoriochromene and encecalin
1989
Abstract The photolysis of the 7-acetoxybenzopyran derivatives 1a-5a has been carried out. Chromene 1a was found to undergo extensive photopolymerization. Chromanone 2a underwent a rather inefficient photo-Fries rearrangement to the 6 - and 8 - acetyl derivatives 2b and 2c . Diacetoxychromene 3a gave the unsaturated ketone 8 as the main product, besides its deacetylation analogue 9 and chromanone 11 . Diacetoxychroman 4a afforded a mixture of four C-acetyl products: 1b, 1c, 2b and 2c , together with Chromene 1a and chromanone 2a. Finally, irradiation of chroman 5a gave rise to a mixture of the two possible photo-Fries products 5b (43%) and 5c (52%). The mechanistic implications of the above…