ArticleLongevity & healthspan2014
A midlife crisis for the mitochondrial free radical theory of aging.
Article in Longevity & healthspan, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 82 citations in OpenAlex.
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- Exploration of Pathogenesis and Cutting-Edge Treatment Strategies of Sarcopenia: A Narrative Review.Clinical interventions in aging · 2025Review
- Reproductive Ageing: Metabolic contribution to age-related chromosome missegregation in mammalian oocytes.Reproduction (Cambridge, England) · 2024Review
- Life-Long Aerobic Exercise is a Non-Pharmacological Approach for Inducing Autophagy and Delaying Muscle Atrophy in the Aging Population.Aging and disease · 2024Review
- Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases.Current issues in molecular biology · 2024Review
- Mitochondria-Targeted Catalase Does Not Suppress Development of Cellular Senescence during Aging.Biomedicines · 2024Article
- Mitochondrial fatty acid beta-oxidation: a possible therapeutic target for skeletal muscle lipotoxicity in peripheral artery disease myopathy.EXCLI journal · 2024Review
- The Evolution and Ecology of Oxidative and Antioxidant Status: A Comparative Approach in African Mole-Rats.Antioxidants (Basel, Switzerland) · 2023Article
- Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge.International journal of molecular sciences · 2023Review
- Exploring the role of host specialisation and oxidative stress in interspecific lifespan variation in subtropical tephritid flies.Scientific reports · 2020Article
- Article
- Causal roles of mitochondrial dynamics in longevity and healthy aging.EMBO reports · 2019Review
- Comparative studies of mitochondrial reactive oxygen species in animal longevity: Technical pitfalls and possibilities.Aging cell · 2019Review
- The exceptional longevity of the naked mole-rat may be explained by mitochondrial antioxidant defenses.Aging cell · 2019Article
- Does senescence promote fitness in Caenorhabditis elegans by causing death?Ageing research reviews · 2019Review
- Mitochondrial DNA Damage Does Not DetermineFrontiers in genetics · 2019Article
- Article
- The Aging Mitochondria.Genes · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since its inception more than four decades ago, the Mitochondrial Free Radical Theory of Aging (MFRTA) has served as a touchstone for research into the biology of aging. The MFRTA suggests that oxidative damage to cellular macromolecules caused by reactive oxygen species (ROS) originating from mitochondria accumulates in cells over an animal's lifespan and eventually leads to the dysfunction and failure that characterizes aging. A central prediction of the theory is that the ability to ameliorate or slow this process should be associated with a slowed rate of aging and thus increased lifespan. A vast pool of data bearing on this idea has now been published. ROS production, ROS neutralization and macromolecule repair have all been extensively studied in the context of longevity. We review experimental evidence from comparisons between naturally long- or short-lived animal species, from calorie restricted animals, and from genetically modified animals and weigh the strength of results supporting the MFRTA. Viewed as a whole, the data accumulated from these studies have too often failed to support the theory. Excellent, well controlled studies from the past decade in particular have isolated ROS as an experimental variable and have shown no relationship between its production or neutralization and aging or longevity. Instead, a role for mitochondrial ROS as intracellular messengers involved in the regulation of some basic cellular processes, such as proliferation, differentiation and death, has emerged. If mitochondrial ROS are involved in the aging process, it seems very likely it will be via highly specific and regulated cellular processes and not through indiscriminate oxidative damage to macromolecules.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.