The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms

Buffenstein, Rochelle; Edrey, Yael H.; Yang, Ting; Mele, James

doi:10.1007/s11357-008-9058-z

Cited by 162 publications

(140 citation statements)

References 89 publications

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“…The description of these results and their impact on the validity and the future of the theory is the main subject of recent reviews in the field [22][23][24][25].…”

Section: Recent Results That Are Incompatible With the Mfrtamentioning

confidence: 99%

Taking a “good” look at free radicals in the aging process

Hekimi

Lapointe

Yang

2011

Trends in Cell Biology

519

373

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The mitochondrial free radical theory of aging (MFRTA) proposes that aging is caused by damage to macromolecules from mitochondrial reactive oxygen species (ROS). This is based on the observed association of the rate of aging and the aged phenotype with the generation of ROS and with oxidative damage. The theory has led to the strong conviction in the general public that the consumption of antioxidants is crucial to health and beneficial to lifespan. However, a variety of recent findings convincingly demonstrate that ROS generation and oxidative damage cannot be the cause of aging. Here we propose that ROS play a role in mediating a stress response to agedependent damage, which could generate the observed correlation between aging and ROS without implying that ROS cause aging. Redefining our understanding of the relationship between ROS and agingMitochondria are a major source of reactive oxygen species (ROS), a type of molecule that includes free radicals such as superoxide. ROS spontaneously oxidize and damage macromolecules such as proteins, lipids and nucleic acids. Cells and organisms are said to be sustaining oxidative stress when an imbalance between ROS generation and detoxification or repair leads to an increase in the level of ROS-dependent damage. The mitochondrial free radical theory of aging (MFRTA) has provided an attractive framework that integrates numerous observations about the generation, the toxicity and the detoxification of ROS, as well as about how these parameters change with the physiological state of cells and organisms and with chronological age. The theory proposes that aging is actually caused by the toxicity of ROS through a vicious cycle in which ROS damage to the constituents of mitochondria leads to the generation of more ROS. The theory is based on numerous observations, including (1) that there is a strong correlation between chronological age and the level of ROS generation and oxidative damage, (2) that mitochondrial function is gradually lost during aging, (3) that inhibition of mitochondrial function can enhance ROS production, and (4) that several age-dependent diseases are associated with severe increases in oxidative stress.The strength of the MFRTA is that it provides a framework for many observations while also stating a plausible causal theory of aging. Furthermore, it provided a clear research program by proposing a theory to be tested as well as by suggesting that decreasing the generation of ROS will result in health benefits. In fact the MFRTA is often taught in textbooks and in *

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“…The description of these results and their impact on the validity and the future of the theory is the main subject of recent reviews in the field [22][23][24][25].…”

Section: Recent Results That Are Incompatible With the Mfrtamentioning

confidence: 99%

Taking a “good” look at free radicals in the aging process

Hekimi

Lapointe

Yang

2011

Trends in Cell Biology

519

373

View full text Add to dashboard Cite

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“…In general, when the level of ROS exceed the normal, it may damage proteins and lipids, even DNA, and it also affects the animal aging and leads to metabolic syndrome and diabetes because of ROS‐induced oxidative stress (Barja, 2002; Brunet‐Rossinni & Austad, 2004; Buffenstein et al., 2008). ROS can also lead to pancreatic β‐cell dysfunction, tissues insulin resistance, and declining insulin production (Brownlee, 2001; Brunner et al., 2009; Kawahito et al., 2009; Vincent, Russell, Low, & Feldman, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…ROS can also lead to pancreatic β‐cell dysfunction, tissues insulin resistance, and declining insulin production (Brownlee, 2001; Brunner et al., 2009; Kawahito et al., 2009; Vincent, Russell, Low, & Feldman, 2004). Follow this point, fruit bats must have the ability to prevent excess production of ROS or reduce oxidative stress raised by a huge fluctuation of blood glucose (Brunner et al., 2009; Buffenstein et al., 2008; Kawahito et al., 2009; Munshi‐South & Wilkinson, 2010; Vincent et al., 2004). However, other researchers hold different opinions.…”

Section: Discussionmentioning

confidence: 99%

“…They thought that there is no unequivocal support that ROS production would give rise to oxidative damage and shorter lifespan. ROS productions are similar between long‐lived and short‐lived mammals, and some long‐lived species even have a higher level of ROS production (Brunet‐Rossinni & Austad, 2004; Buffenstein et al., 2008; Yin et al., 2016). …”

Section: Discussionmentioning

confidence: 99%

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Flight is the key to postprandial blood glucose balance in the fruit batsEonycteris spelaeaandCynopterus sphinx

Peng¹,

He²,

Liu³

et al. 2017

Ecology and Evolution

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Excessive sugar consumption could lead to high blood glucose levels that are harmful to mammalian health and life. Despite consuming large amounts of sugar‐rich food, fruit bats have a longer lifespan, raising the question of how these bats overcome potential hyperglycemia. We investigated the change of blood glucose level in nectar‐feeding bats (Eonycteris spelaea) and fruit‐eating bats (Cynopterus sphinx) via adjusting their sugar intake and time of flight. We found that the maximum blood glucose level of C. sphinx was higher than 24 mmol/L that is considered to be pathological in other mammals. After C. sphinx bats spent approximately 75% of their time to fly, their blood glucose levels dropped markedly, and the blood glucose of E. spelaea fell to the fast levels after they spent 70% time of fly. Thus, the level of blood glucose elevated with the quantity of sugar intake but declined with the time of flight. Our results indicate that high‐intensive flight is a key regulator for blood glucose homeostasis during foraging. High‐intensive flight may confer benefits to the fruit bats in foraging success and behavioral interactions and increases the efficiency of pollen and seed disposal mediated by bats.

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“…1973; Forman and Torres 2002), but in excess can cause DNA, lipid, and protein damage and disrupt cellular function (Harman 1956; Beckman and Ames 1998; Buffenstein et al. 2008). A suite of dietary and endogenous antioxidants (AOX) exists to quench ROS and protect key biomolecules (Finkel and Holbrook 2000).…”

Section: Introductionmentioning

confidence: 99%

Plasma markers of oxidative stress are uncorrelated in a wild mammal

Christensen

Selman

Blount

et al. 2015

Ecology and Evolution

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Oxidative stress, which results from an imbalance between the production of potentially damaging reactive oxygen species versus antioxidant defenses and repair mechanisms, has been proposed as an important mediator of life‐history trade‐offs. A plethora of biomarkers associated with oxidative stress exist, but few ecological studies have examined the relationships among different markers in organisms experiencing natural conditions or tested whether those relationships are stable across different environments and demographic groups. It is therefore not clear to what extent studies of different markers can be compared, or whether studies that focus on a single marker can draw general conclusions regarding oxidative stress. We measured widely used markers of oxidative damage (protein carbonyls and malondialdehyde) and antioxidant defense (superoxide dismutase and total antioxidant capacity) from 706 plasma samples collected over a 4‐year period in a wild population of Soay sheep on St Kilda. We quantified the correlation structure among these four markers across the entire sample set and also within separate years, age groups (lambs and adults), and sexes. We found some moderately strong correlations between some pairs of markers when data from all 4 years were pooled. However, these correlations were caused by considerable among‐year variation in mean marker values; correlation coefficients were small and not significantly different from zero after accounting for among‐year variation. Furthermore, within each year, age, and sex subgroup, the pairwise correlation coefficients among the four markers were weak, nonsignificant, and distributed around zero. In addition, principal component analysis confirmed that the four markers represented four independent axes of variation. Our results suggest that plasma markers of oxidative stress may vary dramatically among years, presumably due to environmental conditions, and that this variation can induce population‐level correlations among markers even in the absence of any correlations within contemporaneous subgroups. The absence of any consistent correlations within years or demographic subgroups implies that care must be taken when generalizing from observed relationships with oxidative stress markers, as each marker may reflect different and potentially uncoupled biochemical processes.

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The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms

Cited by 162 publications

References 89 publications

Taking a “good” look at free radicals in the aging process

Taking a “good” look at free radicals in the aging process

Flight is the key to postprandial blood glucose balance in the fruit batsEonycteris spelaeaandCynopterus sphinx

Plasma markers of oxidative stress are uncorrelated in a wild mammal

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