The free radical theory of aging is dead. Long live the damage theory!

Antioxidants and Redox Signaling

Volumn 20, Issue 4, 2014, Pages 727-731

  Gladyshev, Vadim N ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; FREE RADICAL;

AGING; ARTICLE; CELL DAMAGE; FREE RADICAL THEORY OF AGING; LIFESPAN; MOLECULE; NATURAL SELECTION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; THEORY;

AGING; ANIMALS; HUMANS; LIFE EXPECTANCY; OXIDATION-REDUCTION; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 84892915705     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2013.5228     Document Type: Article

References (32)

1. Anderson RM and Weindruch R. Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol Metab 21: 134-141, 2010.
2. Barzilai N, Guarente L, Kirkwood TB, Partridge L, Rando TA, and Slagboom PE. The place of genetics in ageing research. Nat Rev Genet 13: 589-594, 2012.
3. Binder PM and Danchin A. Life's demons: information and order in biology. What subcellular machines gather and process the information necessary to sustain life? EMBO Rep 12: 495-499, 2011.
4. Blagosklonny MV. Aging: ROS or TOR. Cell Cycle 7: 3344-3354, 2008.
5. Bonawitz ND, Chatenay-Lapointe M, Pan Y, and Shadel GS. Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression. Cell Metab 5: 265-277, 2007.
6. Cabreiro F, Ackerman D, Doonan R, Araiz C, Back P, Papp D, Braeckman BP, and Gems D. Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med 51: 1575-1582, 2011.
7. Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, Matscheski A, Vanfleteren JR, and Gems D. Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev 22: 3236-3241, 2008.
8. Gems D and Doonan R. Antioxidant defense and aging in C. elegans: is the oxidative damage theory of aging wrong? Cell Cycle 8: 1681-1687, 2009.
9. Gladyshev VN. On the cause of aging and control of lifespan: heterogeneity leads to inevitable damage accumulation, causing aging; Control of damage composition and rate of accumulation define lifespan. Bioessays 34: 925-929, 2012.
10. Gladyshev VN. The origin of aging: imperfectness-driven non-random damage defines the aging process and control of lifespan. Trends Genet 29: 506-512, 2013.
11. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 11: 298-300, 1956.
12. Imlay JA. Pathways of oxidative damage. Annu Rev Microbiol 57: 395-418, 2003.
13. Katewa SD and Kapahi P. Dietary restriction and aging, 2009. Aging Cell 9: 105-112, 2010.
14. Kenyon CJ. The genetics of aging. Nature 464: 504-512, 2010.
15. Kirkwood TB and Austad SN. Why do we age? Nature 408: 233-238, 2000.
16. Kirkwood TB and Kowald A. The free-radical theory of ageing-older, wiser and still alive: modelling positional effects of the primary targets of ROS reveals new support. Bioessays 34: 692-700, 2012.
17. Koc A, Gasch AP, Rutherford JC, Kim HY, and Gladyshev VN. Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and-independent components of aging. Proc Natl Acad Sci USA 101: 7999-8004, 2004.
18. Lapointe J and Hekimi S. When a theory of aging ages badly. Cell Mol Life Sci 67: 1-8, 2009.
19. Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, Fink GR, and Guarente L. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418: 344-348, 2002.
20. Linster CL, Van Schaftingen E, and Hanson AD. Metabolite damage and its repair or pre-emption. Nat Chem Biol 9: 72-80, 2013.
21. Mockett RJ, Sohal BH, and Sohal RS. Expression of multiple copies of mitochondrially targeted catalase or genomic Mn superoxide dismutase transgenes does not extend the life span of Drosophila melanogaster. Free Radic Biol Med 49: 2028-2031, 2010.
22. Orgel LE. The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc Natl Acad Sci USA 49: 517-521, 1963.
23. Pani G. P66SHC and ageing: ROS and TOR? Aging 2: 514-518, 2010.
24. Pérez VI, Van Remmen H, Bokov A, Epstein CJ, Vijg J, and Richardson A. The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging Cell 8: 73-75, 2009.
25. RistowM and Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med 51: 327-336, 2011.
26. Sohal RS and Weindruch R. Oxidative stress, caloric restriction, and aging. Science 273: 59-63, 1996.
27. Speakman JR and Selman C. The free-radical damage theory: accumulating evidence against a simple link of oxidative stress to ageing and lifespan. Bioessays 33: 255-259, 2011.
28. Stadtman ER. Protein oxidation and aging. Science 257: 1220-1224, 1992.
29. Tawfik DS. Messy biology and the origins of evolutionary innovations. Nature Chem Biol 6: 692-696, 2010.
30. Van Raamsdonk JM and Hekimi S. Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci USA 109: 5785-5790, 2012.
31. Van Rammsdonk JM and Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5: e1000361, 2009.
32. Zarse K, Schmeisser S, Groth M, Priebe S, Beuster G, Kuhlow D, Guthke R, Platzer M, Kahn CR, and Ristow M. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab 15: 451-465, 2012.