Mechanisms Underlying the Cost of Living in Animals

Hulbert, A. J.; Else, Paul L.

doi:10.1146/annurev.physiol.62.1.207

Cited by 364 publications

(268 citation statements)

References 154 publications

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“…This would not be the case, however, if disease pathogenesis is independent of the physiological mechanisms regulating metabolic rates and longevity. The principal factors driving species differences in basal metabolic rate (BMR) are still not known [29][30][31] . BMR reflects a series of linked metabolic processes, as shown by the similarity in allometric scaling exponents in the equation relating BMR per cell (B c ) to body mass (M), such that B c α M -1/4 for many such processes 21,29 .…”

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

“…The principal factors driving species differences in basal metabolic rate (BMR) are still not known [29][30][31] . BMR reflects a series of linked metabolic processes, as shown by the similarity in allometric scaling exponents in the equation relating BMR per cell (B c ) to body mass (M), such that B c α M -1/4 for many such processes 21,29 . A proposed 'pacemaker' for such interlinked processes is the degree of polyunsaturation of membrane phospholipids, which regulates the activities that contribute the most to cellular energy demand, such as maintenance of sodium and mitochondrial proton gradients (which together account for ∼50% of BMR) [29][30][31][32] .…”

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

“…BMR reflects a series of linked metabolic processes, as shown by the similarity in allometric scaling exponents in the equation relating BMR per cell (B c ) to body mass (M), such that B c α M -1/4 for many such processes 21,29 . A proposed 'pacemaker' for such interlinked processes is the degree of polyunsaturation of membrane phospholipids, which regulates the activities that contribute the most to cellular energy demand, such as maintenance of sodium and mitochondrial proton gradients (which together account for ∼50% of BMR) [29][30][31][32] . The degree of polyunsaturation of most membrane lipids declines with LSP, but this is not the case in the brain or retina, which are unusual in their high requirement for polyunsaturated membrane lipids 29,30 .…”

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

“…A proposed 'pacemaker' for such interlinked processes is the degree of polyunsaturation of membrane phospholipids, which regulates the activities that contribute the most to cellular energy demand, such as maintenance of sodium and mitochondrial proton gradients (which together account for ∼50% of BMR) [29][30][31][32] . The degree of polyunsaturation of most membrane lipids declines with LSP, but this is not the case in the brain or retina, which are unusual in their high requirement for polyunsaturated membrane lipids 29,30 . 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 .…”

Section: Interpreting Allometric Differencesmentioning

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: Interpreting Allometric Differencesmentioning

confidence: 99%

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

Section: Interpreting Allometric Differencesmentioning

confidence: 99%

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Lifespan and mitochondrial control of neurodegeneration

et al. 2004

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“…It is usual to suggest that protein metabolism accounts for a large fraction of total body metabolism. In skeletal muscle, protein turnover reportedly accounts for about 20% of the resting metabolism [9, 188,189], but there are large differences between the various organs, and the turnover rate is expected to show species dependency, i.e., to be highest in small animals [8]. One of us [2] made a calculation for rat cardiac muscle based on a protein turnover of 15% per day, a protein content of 15% wet weight, and a caloric equivalent of 5.9 kJ/g protein [190], which suggested an energy usage of approximately 1.5 mW g Ϫ1 .…”

Section: Contributors To the Energymentioning

confidence: 99%

Cardiac Basal Metabolism.

Gibbs

Loiselle²

2001

JJP

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The cardiac basal metabolism is the rate of energy expenditure of the quiescent myocardium. It is also called the resting metabolism or the arrested heart metabolism. It has been measured in numerous ways, and in vivo there is good evidence that it accounts for about 1/5 to 1/3 of the total energy flux. The difficulty arises, however, when the heart is stopped because the magnitude of the basal metabolism depends, as blood viscosity, on how and under what physiological condition it is measured. It is possible for the in vivo basal value to fall to less than 1/5 of its original value without cellular damage or to increase to values 5 times greater than its probable in vivo magnitude (i.e., to rise to values in excess of the energy flux of the normally beating heart) by altering the composition of the perfusion medium. We have written on this subject several times [1][2][3], but believe that developments in knowledge now make it possible for us to speculate in a more informed manner. Since several million openheart operations are performed on arrested hearts worldwide each year, it would seem imperative that we understand the cellular mechanisms that can change the magnitude of basal metabolism.A. V. Hill [4] has pointed out that in examining physiological activities, it is necessary to assume a baseline from which some quantity or rate can be measured. If the energy flux produced by the beating heart were very large compared with the energy flux of the arrested heart, baseline ambiguity would be relatively unimportant. But this is not so in regard to the heart; its basal metabolism is high. Within a species, the basal metabolism of cardiac tissue is several-fold higher than the resting metabolism of skeletal muscle and is an order of magnitude greater than the resting metabolism of amphibian skeletal muscle.Species differences are clearly evident in the magnitude of cardiac basal metabolism, and we believe that the major reason for these differences relates to the leakiness of cell membranes, such as those of the sarcolemma and sarcoplasmic reticulum and those of Japanese Journal of Physiology, 51, 399-426, 2001 Key words: whole hearts, isolated preparations, biochemical contributors, modifiers, species difference, temperature, substrate, hypoxia. Abstract:We endeavor to show that the metabolism of the nonbeating heart can vary over an extreme range: from values approximating those measured in the beating heart to values of only a small fraction of normal-perhaps mimicking the situation of nonflow arrest during cardiac bypass surgery. We discuss some of the technical issues that make it difficult to establish the magnitude of basal metabolism in vivo. We consider some of the likely contributors to its magnitude and point out that the biochemical reasons for a sizable fraction of the heart's basal ATP usage remain unresolved. We consider many of the physiological factors that can alter the basal metabolic rate, stressing the importance of substrate supply. We point out that the protective effect of hypothermia ...

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Exploration of Energy Metabolism in the Mouse Using Indirect Calorimetry: Measurement of Daily Energy Expenditure (DEE) and Basal Metabolic Rate (BMR)

2015

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Current comprehensive mouse metabolic phenotyping involves studying energy balance in cohorts of mice via indirect calorimetry, which determines heat release from changes in respiratory air composition. Here, we describe the measurement of daily energy expenditure (DEE) and basal metabolic rate (BMR) in mice. These well-defined metabolic descriptors serve as meaningful first-line read-outs for metabolic phenotyping and should be reported when exploring energy expenditure in mice. For further guidance, the issue of appropriate sample sizes and the frequency of sampling of metabolic measurements is also discussed.

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Mechanisms Underlying the Cost of Living in Animals

Cited by 364 publications

References 154 publications

Lifespan and mitochondrial control of neurodegeneration

Lifespan and mitochondrial control of neurodegeneration

Cardiac Basal Metabolism.

Exploration of Energy Metabolism in the Mouse Using Indirect Calorimetry: Measurement of Daily Energy Expenditure (DEE) and Basal Metabolic Rate (BMR)

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