The rate of free radical production as a determinant of the rate of aging: evidence from the comparative approach

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

doi:10.1007/s003600050131

Cited by 333 publications

(210 citation statements)

References 65 publications

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“…To validate the use of LSP as a surrogate for mitochondrial RONS production [16][17][18] , we plotted published rates of RONS formation in 11 species and 4 postmitotic tissues (kidney, heart, brain and liver) [22][23][24][25][26] to show that a strong (r 2 = 0.71 ± 0.15) inverse relationship exists with LSP, with a mean allometric exponent of -0.84 ± 0.34 (Fig. 2).…”

Section: Measuring Rates Of Degenerationmentioning

confidence: 99%

“…Another possible source of allometric differences in BMR is basal proton leak through the mitochondrial inner membrane, which is responsible for ∼20% of BMR and correlates well with LSP in mammals (but not birds) 31,33 . Whatever the mechanisms driving species differences in BMR, they probably do not have a large influence on neurodegeneration, as BMR is poorly correlated with lifespan [16][17][18] . The reasons for species differences in LSP are only partially understood, but evolutionary studies have clarified their origins 18,34 .…”

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

“…Whatever the mechanisms driving species differences in BMR, they probably do not have a large influence on neurodegeneration, as BMR is poorly correlated with lifespan [16][17][18] . The reasons for species differences in LSP are only partially understood, but evolutionary studies have clarified their origins 18,34 . They seem to be the evolutionary consequence of different habitats and lifestyles [16][17][18]34 .…”

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

“…Mitochondria are also the main source of RONS and are implicated in cell and organismal aging, neurodegeneration and apoptosis [16][17][18] . This raises the question as to whether differences in rates of degeneration between species could be related to differences in mitochondrial RONS production, which is thought to be the primary influence on maximum lifespan potential (LSP) [16][17][18] .…”

mentioning

confidence: 99%

“…This raises the question as to whether differences in rates of degeneration between species could be related to differences in mitochondrial RONS production, which is thought to be the primary influence on maximum lifespan potential (LSP) [16][17][18] . We therefore examined the rates of neurodegeneration caused by functionally equivalent mutations in orthologous genes across mammalian species with different LSPs, here used as a surrogate for constitutive RONS formation.…”

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confidence: 99%

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Lifespan and mitochondrial control of neurodegeneration

et al. 2004

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We examine the allometric (comparative scaling) relationships between rates of neurodegeneration resulting from equivalent mutations in a diverse group of genes from five mammalian species with different maximum lifespan potentials. In both retina and brain, rates of neurodegeneration vary by as much as two orders of magnitude and are strongly correlated with maximum lifespan potential and rates of formation of mitochondrial reactive oxygen and nitrogen species (RONS). Cell death in these disorders is directly or indirectly regulated by the intrinsic mitochondrial cell death pathway. Mitochondria are the main source of RONS production and integrate cellular stress signals to coordinate the intrinsic pathway. We propose that these two functions are intimately related and that steadystate RONS-mediated signaling or damage to the mitochondrial stress-integration machinery is the principal factor setting the probability of cell death in response to a diverse range of cellular stressors. This provides a new and unifying framework for investigating neurodegenerative disorders.Cell death in inherited neurodegenerative disorders most commonly occurs by apoptosis 1-4 . The evidence is often indirect and inferred on the basis of characteristic morphological changes, such as chromatin compaction and cell shrinkage, or evidence of caspase activation, but in many cases it is more reliably based on multiple lines of evidence [1][2][3][4] . Caspase-independent cell death also occurs, although the precise mechanisms are less well understood and evidence that this occurs in inherited neurodegenerations is sparse. In these disorders, cell death occurs with a probability that is constant through part or all of the adult lifespan, consistent with a steady-state (one-hit or exponential kinetics) rather than a cumulative damage model 5,6 . The retina is a particularly well understood model of neurodegeneration. Mutations in more than 100 genes are known to cause neurodegeneration of retinal photoreceptors (RetNet; see URL below); these affect virtually all areas of metabolism and all parts of the cell 7-9 .Two main pathways lead to the activation of cysteine proteases or caspases that execute the apoptotic death program [10][11][12] . The extrinsic pathway involves cell-surface signaling complexes (e.g., Fas or FasL), which trigger the cell death cascade by activating caspase 8 and downstream caspases. The intrinsic, or mitochondrial, pathway controls activation of caspase 9, through the adaptor molecule Apaf-1, by regulating release of cytochrome c from mitochondria. Proapoptotic and antiapoptotic members of the Bcl-2 family and various stress and survival signals regulate the release of cytochrome c. Proapoptotic signals can also release proteins such as Smac and Omi, which antagonize IAP (inhibitor of apoptosis) proteins to activate cell death caspases, from the mitochondrial intermembrane space.Evidence from animal models of human photoreceptor degeneration suggests that the mitochondrial, rather than the extrinsic, cell death pa...

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Section: Measuring Rates Of Degenerationmentioning

confidence: 99%

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lifespan and mitochondrial control of neurodegeneration

et al. 2004

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Why do almost all mammals have seven cervical vertebrae? Developmental constraints,Hox genes, and cancer

1999

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Mammals have seven cervical vertebrae, a number that remains remarkably constant. I propose that the lack of variation is caused by developmental constraints: to wit, changes in Hox gene expression, which lead to changes in the number of cervical vertebrae, are associated with neural problems and with an increased susceptibility to early childhood cancer and stillbirths. In vertebrates, Hox genes are involved in the development of the skeletal axis and the nervous system, among other things. In humans and mice, Hox genes have been shown also to be involved in the normal and abnormal (cancer) proliferation of cell lines; several types of cancer in young children are associated with abnormalities in Hox gene expression and congenital anomalies. In these embryonal cancers the incidence of a cervical rib (a rib on the seventh cervical vertebra, a homeotic transformation of a cervical vertebra towards a thoracic-type vertebra) appears to be increased. The minimal estimate of the selection coefficient acting against these mutations is about 12%.In birds and reptiles variations in the number of cervical vertebrae have frequently occurred and there is often intraspecific variability. A review of the veterinary literature shows that cancer rates appear lower in birds and reptiles than in mammals. The low susceptibility to cancer in these classes probably prevents the deleterious pleiotropic effect of neonatal cancer when changes in cervical vertebral number occur.In mammals there is, thus, a coupling between the development of the axial skeleton and other functions (including the proliferations of cell lines). The coupling of functions is either a conserved trait that is also present in reptiles and birds, but without apparent deleterious effects, or the coupling is new to mammals due to a change in the functioning of Hox genes. The cost of the coupling of functions in mammals appears to be an increased risk for neural problems, neonatal cancer, stillbirths, and a constraint on the variability of cervical vertebral number.

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Oxidative Stress and Aging: A Comparison between Vertebrates and Invertebrates

Rizvi

Pandey

2011

Oxidative Stress in Vertebrates and Invertebrates

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The rate of free radical production as a determinant of the rate of aging: evidence from the comparative approach

Cited by 333 publications

References 65 publications

Lifespan and mitochondrial control of neurodegeneration

Lifespan and mitochondrial control of neurodegeneration

Why do almost all mammals have seven cervical vertebrae? Developmental constraints,Hox genes, and cancer

Oxidative Stress and Aging: A Comparison between Vertebrates and Invertebrates

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