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Geroscience. 2017 Dec;39(5-6):499-550. doi: 10.1007/s11357-017-0002-y. Epub 2017 Dec 21.

The Oxygen Paradox, the French Paradox, and age-related diseases.

Author information

1
The Medical Group, Internal Medicine, Rheumatology & Osteoporosis, Dermatology, Pulmonology, Ophthalmology, and Cardiology; the Hospital of the Good Samaritan, Los Angeles, CA, 90017, USA.
2
Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology Center, University of Southern California, Los Angeles, CA, 90089-0191, USA.
3
Lab de Biologie Cellulaire et Végétale, Faculté de Pharmacie, Université de Rennes, 35043, Rennes Cedex, France.
4
Institut de Biologie Paris-Seine (IBPS), UMR CNRS 8256, Biological Adaptation and Ageing, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France.
5
INSERM ERL U1164, 75005, Paris, France.
6
School of Pharmacy, University of Southern California, Los Angeles, CA, 90089-9121, USA.
7
Department of Biochemistry & Molecular Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90033, USA.
8
Département de Médecine nucléaire et Radiobiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada.
9
Institut de Génomique Fonctionnelle de Lyon,ENS de Lyon, CNRS, 69364, Lyon Cedex 07, France.
10
Laboratory for Movement, Sport and Health Sciences-EA 1274, M2S, Université de Rennes 2-ENS, Bruz, 35170, Rennes, France.
11
INSERM UMR 1127-CNRS UMR 7225, Institut du cerveau et de la moelle épinière-ICM Thérapeutique Expérimentale de la Maladie de Parkinson, Université Pierre et Marie Curie, 75651, Paris Cedex 13, France.
12
Huntington Medical Research Institutes, Pasadena, CA, 91105, USA.
13
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
14
Chronic infections and Immune ageing, INSERM U1135, Hopital Pitie-Salpetriere, Pierre et Marie Curie University, 75013, Paris, France.
15
INSERM Equipe 14 Institut de la Vision, 75012, Paris, France.
16
Department of Molecular Medicine, University of Padova, 35121, Padova, Italy.
17
Los Angeles Cardiology Associates, Hospital of the Good Samaritan, Los Angeles, CA, 90017, USA.
18
Division of Neurobiology, Department of Biological Sciences of the Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, 90089-0191, USA.
19
Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90033, USA.
20
Lipid peroxidation, Signalling and Vascular Diseases INSERM U1048, 31432, Toulouse Cedex 4, France.
21
Stress and Cancer Laboratory, Institut Curie-Inserm U830, 75248, Paris Cedex 05, France.
22
Laboratoire de Signalisation et Physiopathologie Cardiovasculaire-Inserm UMR-S 1180, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, Paris, France.
23
Department of Radiation Oncology, Hospital of the Good Samaritan, Los Angeles, CA, 90017, USA.
24
Department of Oncology & Hematology, Hospital of the Good Samaritan, Los Angeles, CA, 90017, USA.
25
Division of Molecular & Computational Biology, Department of Biological Sciences of the Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, 90089-0191, USA.
26
Children's Hospital of Los Angeles, Developmental Biology, Regenerative Medicine and Stem Cell Therapeutics program and the Center for Environmental Impact on Global Health Across the Lifespan at The Saban Research Institute, Los Angeles, CA, 90027, USA.
27
Department of Pediatrics, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90033, USA.
28
DR Saint-Antoine UMR_S938, UPMC, Inserm Faculté de Médecine, Université Pierre et Marie Curie, 75012, Paris, France.
29
Scientific Service of the Embassy of France in the USA, Consulate General of France in Los Angeles, Los Angeles, CA, 90025, USA.
30
Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology Center, University of Southern California, Los Angeles, CA, 90089-0191, USA. kelvin@usc.edu.
31
Department of Biochemistry & Molecular Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90033, USA. kelvin@usc.edu.
32
Division of Molecular & Computational Biology, Department of Biological Sciences of the Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, 90089-0191, USA. kelvin@usc.edu.

Abstract

A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen "a toxic environmental poison" could be also indispensable for life (Beckman and Ames Physiol Rev 78(2):547-81, 1998; Stadtman and Berlett Chem Res Toxicol 10(5):485-94, 1997)?: the so-called Oxygen Paradox (Davies and Ursini 1995; Davies Biochem Soc Symp 61:1-31, 1995). How can French people apparently disregard the rule that high dietary intakes of cholesterol and saturated fats (e.g., cheese and paté) will result in an early death from cardiovascular diseases (Renaud and de Lorgeril Lancet 339(8808):1523-6, 1992; Catalgol et al. Front Pharmacol 3:141, 2012; Eisenberg et al. Nat Med 22(12):1428-1438, 2016)?: the so-called, French Paradox. Doubtless, the truth is not a duality and epistemological bias probably generates apparently self-contradictory conclusions. Perhaps nowhere in biology are there so many apparently contradictory views, and even experimental results, affecting human physiology and pathology as in the fields of free radicals and oxidative stress, antioxidants, foods and drinks, and dietary recommendations; this is particularly true when issues such as disease-susceptibility or avoidance, "healthspan," "lifespan," and ageing are involved. Consider, for example, the apparently paradoxical observation that treatment with low doses of a substance that is toxic at high concentrations may actually induce transient adaptations that protect against a subsequent exposure to the same (or similar) toxin. This particular paradox is now mechanistically explained as "Adaptive Homeostasis" (Davies Mol Asp Med 49:1-7, 2016; Pomatto et al. 2017a; Lomeli et al. Clin Sci (Lond) 131(21):2573-2599, 2017; Pomatto and Davies 2017); the non-damaging process by which an apparent toxicant can activate biological signal transduction pathways to increase expression of protective genes, by mechanisms that are completely different from those by which the same agent induces toxicity at high concentrations. In this review, we explore the influences and effects of paradoxes such as the Oxygen Paradox and the French Paradox on the etiology, progression, and outcomes of many of the major human age-related diseases, as well as the basic biological phenomenon of ageing itself.

KEYWORDS:

Adaptive Homeostasis; Age-related diseases; Ageing; French Paradox; Healthspan; Oxidative stress; Oxygen Paradox; Proteostasis

PMID:
29270905
PMCID:
PMC5745211
DOI:
10.1007/s11357-017-0002-y
[Indexed for MEDLINE]
Free PMC Article

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