A decrease of free radical production near critical targets as a cause of maximum longevity in animals

Barja, Gustavo; Cadenas, Susana; Rojas, C.; López-Torres, Mónica; Pérez‐Campo, R.

doi:10.1016/0305-0491(94)90103-1

Cited by 88 publications

(64 citation statements)

References 41 publications

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“…Previous studies have suggested that the relationship between energy expenditure and lifespan is a consequence of the association of high mass-specific levels of DEE and RMR with high production of mitochondrial reactive oxygen species (ROS). Consistent with this idea, an inverse relationship between ROS production in various tissues and life span has been found in several species (Sohal et al 1989(Sohal et al , 1990Ku et al 1993;Barja et al 1994). In our analysis, however, DEE and RMR were not significantly related to MLSP in birds after the effects of body mass and phylogeny were accounted for.…”

Section: Discussionsupporting

confidence: 56%

Energetics and longevity in birds

Furness

Speakman

2008

AGE

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The links between energy expenditure and ageing are different at different levels of enquiry. When studies have examined the relationships between different species within a given class the association is generally negative-animals with greater metabolism per gram of tissue live shorter lives. Within species, or between classes (e.g. between birds and mammals) the association is the opposite-animals with higher metabolic rates live longer. We have previously shown in mammals that the negative association between lifespan and metabolic rate is in fact an artefact of using resting rather than daily energy expenditure, and of failing to adequately take into account the confounding effects of body size and the lack of phylogenetic independence of species data. When these factors are accounted for, across species of mammals, the ones with higher metabolism also have the largest lifetime expenditures of energy-consistent with the inter-class and intra-specific data. A previous analysis in birds did not yield the same pattern, but this may have been due to a lack of sufficient power in the analysis. Here we present an analysis of a much enlarged data set (>300 species) for metabolic and longevity traits in birds. These data show very similar patterns to those in mammals. Larger individuals have longer lives and lower per-gram resting and daily energy expenditures, hence there is a strong negative relationship between longevity and mass-specific metabolism. This relationship disappears when the confounding effects of body mass and phylogeny are accounted for. Across species of birds, lifetime expenditure of energy per gram of tissue based on both daily and resting energy expenditure is positively related to metabolic intensity, mirroring these statistical relationships in mammals and synergising with the positive associations of metabolism with lifespan within species and between vertebrate classes.

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Section: Discussionsupporting

confidence: 56%

Energetics and longevity in birds

Furness

Speakman

2008

AGE

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“…The idea that free radical production (more specifically 02; production) is more important for the determination of lifespan than free radical scavenging has been formulated by three previous authors (12,23,24,46,146,147). Sohal etal collected the initial correlational data and formulated the concept that rate of O~; production is a lifespan determinant (12), however these authors placed equal emphasis on free radical scavenging and since then have tended to focus on increasing free radical scavenging as a way to test the free radical theory of aging (48,148,149).…”

Section: The Rate Of 02; Production Controls Lifespan Independently Omentioning

confidence: 99%

“…Sohal etal collected the initial correlational data and formulated the concept that rate of O~; production is a lifespan determinant (12), however these authors placed equal emphasis on free radical scavenging and since then have tended to focus on increasing free radical scavenging as a way to test the free radical theory of aging (48,148,149). Since he observed that endogenous antioxidants are negatively correlated with maximum longevity, Barja proposed that it is oxygen free radical generation in mitochondria, not antioxidants, that determines, in part, aging (21,22,24,25,146). Barja argues that mitochondrial DNA, due to its proximity to the source of free radical production, the electron transport chain, suffers a high level of damage due to increased local concentration of oxygen free radicals.…”

Section: The Rate Of 02; Production Controls Lifespan Independently Omentioning

confidence: 99%

“…Barja argues that mitochondrial DNA, due to its proximity to the source of free radical production, the electron transport chain, suffers a high level of damage due to increased local concentration of oxygen free radicals. Due to the fact that this damage is very local, Barja argues that it cannot be prevented by general antioxidants such as SOD, CAT and glutathione peroxidase (21,22,24,25,46,47,146). This argument is strengthened when considering that, due to the high surface density of the inner mitochondrial membrane, most macromolecules of the mitochondrial matrix are in fact adjacent to the inner mitochondrial membrane (150).…”

Section: The Rate Of 02; Production Controls Lifespan Independently Omentioning

confidence: 99%

“…Before even contemplating such a demanding endeavor, a question has to be conclusively answered first. This question is whether the interspecies variation in the rate of O2.--/H202 production reported by Barja and Sohal (12,[25][26][27]30,32,33,35,47,146,178) is due to variation in the proprieties of individual Complexes (Complex I and III) or whether this is due to variation in the properties of the whole mitochondria (or even the organism as a whole). For example, it is possible that the steady state strength of the membrane potential is lower in birds than in mammals.…”

Section: Tests For the Postulated Hypothesismentioning

confidence: 99%

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The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Muller

2000

AGE

122

123

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Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/ transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity. This paper aims to summarize what is known about the nature and mechanisms of superoxide production and what genes are involved in controlling the rate of superoxide production.

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Reactive oxygen metabolites, antioxidants and head and neck cancer

1999

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This manuscript will review the probable role of reactive oxygen metabolites (ROM) in the etiopathogenesis of head and neck cancer (HNC). Cancer is a heterogeneous disorder with multiple etiologies including somatic and germ‐line mutations, cellular homeostatic disturbances, and environmental triggers. Certain etiologies are characteristic of HNC and include infectious agents such as the Epstein‐Barr virus, the use of tobacco, and consumption of alcohol. A large body of evidence implicates ROM in tumor formation and promotion. ROM species are formed in the process of cellular respiration, specifically during oxidative phosphorylation. These ubiquitous molecules are highly toxic in the cellular environment. Of the many effects of ROM, especially important are their effect on DNA. Specifically, ROM cause a variety of DNA damage, including insertions, point mutations, and deletions. Thus, it is hypothesized that ROM may be critically involved in the etiology of malignant disease through their possible impact on protooncogenes and tumor suppressor genes. Additionally, empirical evidence suggests that ROM may also affect the balance between apoptosis and cellular proliferation. If apoptotic mechanisms are overwhelmed, uncontrolled cellular proliferation may follow, potentially leading to tumor formation. Thus, this manuscript will critically review the evidence that supports the role of ROM in tumorigenesis. ROM scavengers and blockers have shown both in vivo and in vitro effects of attenuating the toxicity of ROM. Such compounds include the antioxidant vitamins (A, C, and E), nutrient trace elements (selenium), enzymes (superoxide dismutase, glutathione peroxidase, and catalase), hormones (melatonin), and a host of natural and synthetic compounds (lazaroids, allopurinol, gingko extract). Thus, this paper will also review the possible benefit derived from the use of such scavengers/blockers in the prevention of HNC. © 1999 John Wiley & Sons, Inc. Head Neck 21: 467–479, 1999.

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A decrease of free radical production near critical targets as a cause of maximum longevity in animals

Cited by 88 publications

References 41 publications

Energetics and longevity in birds

Energetics and longevity in birds

The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Reactive oxygen metabolites, antioxidants and head and neck cancer

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