The role of oxidative damage in mitochondria during aging: a review

Huang, Hai; Mantón, Kenneth G.

doi:10.2741/1298

Cited by 120 publications

(95 citation statements)

References 206 publications

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“…Huang and Manton, 2004;Fukagawa, 1999;Finkel and Holbrook, 2000;Golden et al, 2002;Dufour and Larsson, 2004). Surprisingly, despite their evident synergies, while the free-radical theory has blossomed, the rate of living theory by contrast has fallen into general disrepute.…”

Section: Historical Perspectivementioning

confidence: 99%

Body size, energy metabolism and lifespan

Speakman

2005

Journal of Experimental Biology

757

637

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Bigger animals live longer. The scaling exponent for the relationship between lifespan and body mass is between 0.15 and 0.3. Bigger animals also expend more energy, and the scaling exponent for the relationship of resting metabolic rate (RMR) to body mass lies somewhere between 0.66 and 0.8. Mass-specific RMR therefore scales with a corresponding exponent between -0.2 and -0.33. Because the exponents for mass-specific RMR are close to the exponents for lifespan, but have opposite signs, their product (the mass-specific expenditure of energy per lifespan) is independent of body mass (exponent between -0.08 and 0.08). This means that across species a gram of tissue on average expends about the same amount of energy before it dies regardless of whether that tissue is located in a shrew, a cow, an elephant or a whale. This fact led to the notion that ageing and lifespan are processes regulated by energy metabolism rates and that elevating metabolism will be associated with premature mortalitythe rate of living theory.The free-radical theory of ageing provides a potential mechanism that links metabolism to ageing phenomena, since oxygen free radicals are formed as a by-product of oxidative phosphorylation. Despite this potential synergy in these theoretical approaches, the free-radical theory has grown in stature while the rate of living theory has fallen into disrepute. This is primarily because comparisons made across classes (for example, between birds and mammals) do not conform to the expectations, and even within classes there is substantial interspecific variability in the mass-specific expenditure of energy per lifespan. Using interspecific data to test the rate of living hypothesis is, however, confused by several major problems. For example, appeals that the resultant lifetime expenditure of energy per gram of tissue is 'too variable' depend on the biological significance rather than the statistical significance of the variation observed. Moreover, maximum lifespan is not a good marker of ageing and RMR is not a good measure of total energy metabolism. Analysis of residual lifespan against residual RMR reveals no significant relationship. However, this is still based on RMR.A novel comparison using daily energy expenditure (DEE), rather than BMR, suggests that lifetime expenditure of energy per gram of tissue is NOT independent of body mass, and that tissue in smaller animals expends more energy before expiring than tissue in larger animals. Some of the residual variation in this relationship in mammals is explained by ambient temperature. In addition there is a significant negative relationship between residual lifespan and residual daily energy expenditure in mammals. A potentially much better model to explore the links of body size, metabolism and ageing is to examine the intraspecific links. These studies have generated some data that support the original rate of living theory and other data that conflict. In particular several studies have shown that manipulating animals to expend more or less energy ...

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Section: Historical Perspectivementioning

confidence: 99%

Body size, energy metabolism and lifespan

Speakman

2005

Journal of Experimental Biology

757

637

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“…Mitochondrial ROS production plays a central role in the age-associated decline in tissue function [18][19][20]. Mitochondrial generated ROS, produced by in vivo electron leakage from ETC CI and CIII play a key role in the modification of mitochondrial proteins [18,[21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes

Choksi

Papaconstantinou

2008

Free Radical Biology and Medicine

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Mitochondrial generated ROS increases with age and is a major factor that damages proteins by oxidative modification. Accumulation of oxidatively damaged proteins has been implicated as a causal factor in the age-associated decline in tissue function. Mitochondrial electron transport chain (ETC) complexes I and III are the principle sites of ROS production, and oxidative modifications to their complex subunits inhibit their in vitro activity. We hypothesize that mitochondrial complex subunits may be primary targets for modification by ROS which may impair normal complex activity. This study of heart mitochondria from young, middle-aged and old mice reveals that there is an agerelated decline in complex I and V activities that correlate with increased oxidative modification to their subunits. The data also show a specificity for modifications of the ETC complex subunits, i.e., several proteins have more than one type of adduct. We postulate that the electron leakage from ETC complexes causes specific damage to their subunits and increased ROS generation as oxidative damage accumulates, leading to further mitochondrial dysfunction, a cyclical process that underlies the progressive decline in physiologic function of aged mouse heart.

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“…Over time, damage from these reactive oxygen species (ROS) is thought to be an important aspect of the aging process, encapsulated in the free-radical theory of aging (Huang and Manton, 2004;Fukagawa, 1999;Finkel and Holbrook, 2000;Golden et al, 2002;Dufour and Larsson, 2004). Some level of oxidants, particularly H 2 O 2 , is thought to be essential for cell survival because of their role in gene regulation, cell signaling and apoptosis (Sohal and Orr, 2012).…”

Section: Introductionmentioning

confidence: 99%

Linkages between the life-history evolution of tropical and temperate birds and the resistance of their cells to oxidative and non-oxidative chemical injury

Jiménez

Harper

Queenborough

et al. 2012

Journal of Experimental Biology

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SUMMARYA fundamental challenge facing physiological ecologists is to understand how variation in life history at the whole-organism level might be linked to cellular function. Thus, because tropical birds have higher annual survival and lower rates of metabolism, we hypothesized that cells from tropical species would have greater cellular resistance to chemical injury than cells from temperate species. We cultured dermal fibroblasts from 26 tropical and 26 temperate species of birds and examined cellular resistance to cadmium, H 2 O 2 , paraquat, thapsigargin, tunicamycium, methane methylsulfonate (MMS) and UV light. Using ANCOVA, we found that the values for the dose that killed 50% of cells (LD 50 ) from tropical birds were significantly higher for H 2 O 2 and MMS. When we tested for significance using a generalized least squares approach accounting for phylogenetic relationships among species to model LD 50 , we found that cells from tropical birds had greater tolerance for Cd, H 2 O 2 , paraquat, tunicamycin and MMS than cells from temperate birds. In contrast, tropical birds showed either lower or no difference in tolerance to thapsigargin and UV light in comparison with temperate birds. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to be more resistant to forms of oxidative and non-oxidative stress than cells from shorterlived temperate species.Supplementary material available online at

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The role of oxidative damage in mitochondria during aging: a review

Cited by 120 publications

References 206 publications

Body size, energy metabolism and lifespan

Body size, energy metabolism and lifespan

Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes

Linkages between the life-history evolution of tropical and temperate birds and the resistance of their cells to oxidative and non-oxidative chemical injury

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