Does the oxidative stress theory of aging explain longevity differences in birds? I. Mitochondrial ROS production
Highlights
► Parrots as a group live 5–7 times longer than same-sized quails. ► To date, the reason for their long lifespan is still not known. ► Reactive oxygen species (ROS) production is associated with lifespan differences. ► Mitochondrial ROS production was measured in heart, liver, muscle and erythrocytes. ► ROS production did not correspond with the observed longevity differences.
Introduction
The oxidative stress theory of aging gained considerable support when Sohal and colleagues discovered that the rates of superoxide and hydrogen peroxide production of liver, heart and kidney mitochondria were inversely related to maximum lifespan potential (MLSP) in mammals (Sohal et al., 1990, Ku et al., 1993). Because the mammal species they studied differed significantly in size, the extent to which interspecific differences in MLSP were attributable to size effects versus differences in rates of mitochondrial formation of reactive oxygen species (ROS) was unclear. This led the group to compare mitochondrial ROS production in short-living rats (MLSP 5y) to that of similar-sized but long-living pigeons (MLSP 35y). They found mitochondrial ROS production to be significantly lower in brain, heart and kidney of pigeons, from which they concluded that pigeon tissues were under less oxidative stress than those of rats (Ku and Sohal, 1993). Subsequent studies have extended this comparison by using different tissues and substrates for the mitochondrial respiration chain, and also conclude that mitochondrial ROS production is higher in rats compared to pigeons (Barja et al., 1994, Herrero and Barja, 1997, Barja, 1998, Lambert et al., 2007, Lambert et al., 2010). Although the finding that heart mitochondria of short-living mice (MLSP 4y) have higher ROS production rates than those of long-living budgerigars (MSLP 21y) and canaries (MLSP 24y) (Herrero and Barja, 1998) further supports the oxidative stress theory of aging, Brown et al. (2009) challenge this generality by showing that liver mitochondria from mice have a lower rate of ROS production compared to longer-living house sparrows (MLSP 14y).
While previous comparative studies mainly support the oxidative stress theory of aging, the extent to which variation in mitochondrial ROS production is responsible for differences in MLSP among species is far from certain. Most conclusions are based mainly on studies comparing isolated heart mitochondria using succinate as a respiratory chain substrate. In some cases, however, different conclusions are reached when using other substrates or other tissues. For example, whereas the Barja group demonstrated a higher ROS production in pyruvate-supplemented heart mitochondria of the rat in comparison to the pigeon (Herrero and Barja, 1997), Lambert et al. (2007) did not find a relationship between heart mitochondrial ROS generation and MLSP in a variety of mammals and birds using pyruvate, but did so when providing succinate. Similarly, the relationship between MLSP and mitochondrial ROS production originally reported for liver (Barja et al., 1994) was not observed for glutamate/malate- or succinate-supplemented liver mitochondria (Brown et al., 2009).
While mammal–bird longevity differences make them well suited for examining the bases of aging, there has been surprisingly little comparative examination of ROS production rates among bird species with very different MLSP. Here we report a comparison of mitochondrial ROS production of three tissues from two short-living and three long-living bird species that exhibit, on average, 5-fold longevity differences. The two quail species (king quails and Japanese quails) and the three parrot species (budgerigars, lovebirds and cockatiels) overlap in size, but the quails are very short-living and the parrots are very long-living among bird species (Fig.1). Although traits, including MLSP, among closely related species cannot be considered to be statistically independent if phylogenetic signals strongly influence the evolution of those traits (Felsenstein, 1985), the oxidative stress theory of aging predicts convergent evolution of mechanisms responsible for longevity.
Traditionally, mitochondrial ROS generation has been determined using enzymatic detection of hydrogen peroxide production by isolated mitochondria (Barja, 2002). Extrapolation from these in vitro measurements to the in vivo situation is difficult because little is known about changes in mitochondrial superoxide production in response to physiologically relevant changes in substrate supply and energy demand in intact cells. Some of these uncertainties are alleviated by using fluorescent dyes, such as Dihydrorhodamine 123 or MitoSox Red to infer cellular and mitochondrial ROS production in intact cells (Wardman, 2007). Birds, in contrast to mammals, have nucleated erythrocytes that also possess mitochondria and other organelles; thus permitting ROS production to be analyzed in whole cells in their physiological cell environment. We have therefore determined ROS production both in intact red blood cells and in mitochondria isolated from three tissues (heart, skeletal muscle and liver) of the five bird species. ROS production of isolated mitochondria was determined under physiological substrate concentrations of succinate and pyruvate at assay temperatures representing normal bird body temperature. These measurements were undertaken in the absence and presence of the complex III inhibitor antimycin A to assess basal and maximal rates of ROS production, respectively.
Section snippets
Holding conditions
All experiments were approved by the University of Wollongong Animal Ethics Committee and were conducted in conformity with the NHMRC Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. Six male budgerigars (Melopsittacus undulatus) (MLSP = 21 y; average mass = 26.0 g) derived from wild-type native budgerigars were purchased from a bird breeder in Queensland, Australia. Ten Japanese quails (Coturnix japonica) (MLSP = 6 y; average mass = 221.2 g) were purchased from Kyeema
ROS production in erythrocytes
The production of hydroxyl radicals and peroxynitrate (determined over a 30 min period using Dihydrorhodamine 123) was highly variable, with king quail erythrocytes exhibiting the lowest and the budgerigar erythrocytes showing the highest fluorescence, but with no significant difference between the other species (Fig. 2A).
Although there are significant differences in erythrocyte superoxide production between individual species, there is no general pattern between short-living quails and
Discussion
The common view that mitochondrial ROS production is higher in short-living species compared to long-living species has been historically based on either bird–mammal (e.g. Ku and Sohal, 1993, Barja et al., 1994, Herrero and Barja, 1997, Lambert et al., 2007) or within-mammal comparisons (e.g. Sohal et al., 1990). To our knowledge, ours is the first study to compare mitochondrial ROS production among birds with substantial variation in MLSP. The approximately 5-fold difference in MLSP between
Acknowledgments
We gratefully acknowledge the assistance on diet formulation provided by Kirk C. Klasing and Ron Newman. This research was supported by funding from the Australian Research Council. The study was conceived and planned by all three authors; the experiments were carried out by M.K. Montgomery and the manuscript was written by all three authors.
References (38)
- et al.
Cytochemical and functional characterization of blood and inflammatory cells from the lizard Ameiva ameiva
Tissue Cell
(2005) - et al.
Time course of ROS production in skeletal muscle mitochondria from chronic heat-exposed broiler chicken
Comp. Biochem. Physiol. A Mol. Integr. Physiol.
(2010) - et al.
Examining the mechanisms responsible for lower ROS release rates in liver mitochondria from the long-lived house sparrow (Passer domesticus) and big brown bat (Eptesicus fuscus) compared to the short-lived mouse (Mus musculus)
Mech. Ageing Dev.
(2009) Effect of Ca2 + on coupling of rat liver mitochondria
FEBS Lett.
(1974)- et al.
Determination of serum proteins by means of the biuret reaction
J. Biol. Chem.
(1949) - et al.
Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization
J. Biol. Chem.
(2008) - et al.
Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon
Mech. Ageing Dev.
(1997) - et al.
H2O2 production of heart mitochondria and aging rate are slower in canaries and parakeets than in mice: sites of free radical generation and mechanisms involved
Mech. Ageing Dev.
(1998) - et al.
The phosphorus/oxygen ratio of mitochondrial oxidative phosphorylation
J. Biol. Chem.
(1979) - et al.
Total-body hematocrit iron kinetics and erythrocyte life-span in pigeons (Columba livia)
Comp. Biochem. Physiol. A Physiol.
(1989)
Comparison of mitochondrial proxidant generation and antioxidant defenses between rat and pigeon — possible basis of variation in longevity and metabolic potential
Mech. Ageing Dev.
Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species
Free Radic. Biol. Med.
Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I)
J. Biol. Chem.
Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria
Free Radic. Biol. Med.
O2 solubility in aqueous media determined by a kinetic method
Anal. Biochem.
Hydrogen peroxide production by liver mitochondria in different species
Mech. Ageing Dev.
Topology of superoxide production from different sites in the mitochondrial electron transport chain
J. Biol. Chem.
Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects
Free Radic. Biol. Med.
Mitochondrial free radical production and aging in mammals and birds
Ann. N. Y. Acad. Sci.
Cited by (42)
Does high mitochondrial efficiency carry an oxidative cost? The case of the African pygmy mouse (Mus mattheyi)
2022, Comparative Biochemistry and Physiology -Part A : Molecular and Integrative PhysiologyCitation Excerpt :Although the link between aerobic metabolism, mitochondrial inefficiency and reactive oxygen species (ROS) production may explain some variations in the metabolic traits between individuals (Brand, 2000; Speakman et al., 2004), it is not systematically observed. For instance, inter-species comparisons most often show that mitochondria from small species in different taxa (e.g., mammals, frogs, and birds) exhibit higher proton leakage and lower coupling efficiency at rest, but higher ROS release than those from large species (Sohal and Weindruch, 1996; Lambert et al., 2007; Montgomery et al., 2012; Roussel et al., 2015; Voituron et al., 2020). In light of this, it is difficult to predict the production of reactive oxygen species in extremely small species such as M. mattheyi.
Blood
2022, Sturkie's Avian PhysiologyMitochondrial threshold for H<inf>2</inf>O<inf>2</inf> release in skeletal muscle of mammals
2020, MitochondrionCitation Excerpt :Consequently, all studies found a negative correlation between the specific oxygen consumption and body mass at all levels of organization, from whole body to cell and mitochondria. However, regarding mitochondrial ROS production and body mass, similar pattern is often observed in different taxa (Sohal et al., 1989, 1990; Ku et al., 1993; Sohal and Weindruch, 1996; Csiszar et al., 2012; Roussel et al., 2015), but not systematically so (e.g. depending on the substrate used) (Lambert et al., 2007; Csiszar et al., 2012; Montgomery et al., 2012). One part of the discrepancies between studies could be explained by the fact that mitochondrial generation of ROS is a complex process which results in the sum of rates from up to eleven mitochondrial sites involved in substrate oxidation and electron transport (Brand, 2016).
Gerontology of Psittacines
2020, Veterinary Clinics of North America - Exotic Animal PracticeCitation Excerpt :The natural history of birds has shown quite the opposite. Studies have shown that superoxide and hydrogen peroxide production rates were inversely related to the maximum life span potential in some species of mammals.15 To clarify if the difference in maximum life span potential between species was attributable to size or ROS production, ROS production was compared between rats and pigeons, 2 similar-sized animals with different maximum life span potential.
Birds as models for the biology of aging and aging-related disease: An update
2018, Conn's Handbook of Models for Human Aging