Oxygen and Aging

Annual Review of Gerontology and Geriatrics

Volumn 34, Issue 1, 2014, Pages 59-92

  Pitt, Jason N ^a   Leiser, Scott F ^a   Kaeberlein, M ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE DEACETYLASE; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1; MAMMALIAN TARGET OF RAPAMYCIN; OXYGEN; PROTEASOME; RAPAMYCIN; REACTIVE OXYGEN METABOLITE; SIRTUIN;

AEROBIC METABOLISM; AGING; AUTOPHAGY; CAENORHABDITIS ELEGANS; CELL HYPOXIA; CELL PROLIFERATION; CELL SURVIVAL; DEACETYLATION; DIET RESTRICTION; GENE MUTATION; HEALTH STATUS; HUMAN; HYPEROXIA; HYPOXIA; LIFE EXTENSION; LIFESPAN; LONGEVITY; MAMMAL; NONHUMAN; NUTRIENT AVAILABILITY; OXIDATIVE STRESS; OXYGEN CONCENTRATION; OXYGEN CONSUMPTION; PHYLUM; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION;

EID: 84943191525     PISSN: 01988794     EISSN: 19444036     Source Type: Book Series    
DOI: 10.1891/0198-8794.34.59     Document Type: Chapter

References (176)

1. Ackerman, D., Gems, D. (2012). Insulin/IGF-1 and hypoxia signaling act in concert to regulate iron homeostasis in caenorhabditis elegans. PLoS Genetics, 8 (3), e1002498. http://dx.doi.org/10.1371/journal.pgen.1002498
2. Austad, S. N., Fischer, K. E. (1991). Mammalian aging, metabolism, and ecology: Evidence from the bats and marsupials. Journal of Gerontology, 46 (2), B47-B53.
3. Barros, M. H., Bandy, B., Tahara, E. B., Kowaltowski, A. J. (2004). Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae. The Journal of Biological Chemistry, 279 (48), 49883-49888. http://dx.doi.org/10.1074/jbc.M408918200
4. Bellier, A., Chen, C.-S., Kao, C.-Y., Cinar, H. N., Aroian, R. V. (2009). Hypoxia and the hypoxic response pathway protect against pore-forming toxins in C. elegans. PLoS Pathogens, 5 (12), e1000689. http://dx.doi.org/10.1371/journal.ppat.1000689
5. Benderro, G. F., Lamanna, J. C. (2011). Hypoxia-induced angiogenesis is delayed in aging mouse brain. Brain Research, 1389, 50-60. http://dx.doi.org/10.1016/ j.brainres.2011.03.016
6. Benita, Y., Kikuchi, H., Smith, A. D., Zhang, M. Q., Chung, D. C., Xavier, R. J. (2009). An integrative genomics approach identifi es Hypoxia Inducible Factor-1 (HIF-1)- target genes that form the core response to hypoxia. Nucleic Acids Research, 37 (14), 4587-4602. http://dx.doi.org/10.1093/nar/gkp425
7. Bishop, T., Lau, K. W., Epstein, A. C. R., Kim, S. K., Jiang, M., O'Rourke, D., Ratcliffe, P. J. (2004). Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans. PLoS Biology, 2 (10), e289. http:// dx.doi.org/10.1371/journal.pbio.0020289
8. Bjedov, I., Toivonen, J. M., Kerr, F., Slack, C., Jacobson, J., Foley, A., Partridge, L. (2010). Mechanisms of life span extension by rapamycin in the fruit fl y Drosophila melanogaster. Cell Metabolism, 11 (1), 35-46. http://dx.doi.org/10.1016/j.cmet.2009.11.010
9. Bolli, R., Marbán, E. (1999). Molecular and cellular mechanisms of myocardial stunning. Physiological Reviews, 79 (2), 609-634.
10. Braeckman, B. P., Houthoofd, K., Vanfleteren, J. R. (2002). Assessing metabolic activity in aging Caenorhabditis elegans: Concepts and controversies. Aging Cell, 1 (2), 82-88. http://dx.doi.org/10.1046/j.1474-9728.2002.00021.x
11. Burtner, C. R., Murakami, C. J., Kennedy, B. K., Kaeberlein, M. (2009). A molecular mechanism of chronological aging in yeast. Cell Cycle (Georgetown, Tex.), 8 (8), 1256-1270.
12. Calabrese, E. J., Baldwin, L. A. (2001). The frequency of U-shaped dose responses in the toxicological literature. Toxicological Sciences, 62 (2), 330-338. http://dx.doi.org/10.1093/toxsci/62.2.330
13. Chang, A. J., Chronis, N., Karow, D. S., Marletta, M. A., Bargmann, C. I. (2006). A distributed chemosensory circuit for oxygen preference in C. elegans. PLoS Biology, 4 (9), e274. http://dx.doi.org/10.1371/journal.pbio.0040274
14. Chen, D., Thomas, E. L., Kapahi, P. (2009). HIF-1 modulates dietary restrictionmediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genetics, 5 (5), e1000486. http://dx.doi.org/10.1371/journal.pgen.1000486
15. Chen, H., Xiong, T., Qu, Y., Zhao, F., Ferriero, D., Mu, D. (2012). mTOR activates hypoxia-inducible factor-1 α and inhibits neuronal apoptosis in the developing rat brain during the early phase after hypoxia-ischemia. Neuroscience Letters, 507 (2), 118-123. http://dx.doi.org/10.1016/j.neulet.2011.11.058
16. Choi, D., Cai, E. P., Schroer, S. A., Wang, L., Woo, M. (2011). Vhl is required for normal pancreatic β cell function and the maintenance of β cell mass with age in mice. Laboratory Investigation, 91 (4), 527-538. http://dx.doi.org/10.1038/ labinvest.2010.207
17. Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Weindruch, R. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science (New York, N.Y.), 325 (5937), 201-204. http:// dx.doi.org/10.1126/science.1173635
18. Conti, B. (2008). Considerations on temperature, longevity and aging. Cellular and Molecular Life Sciences: CMLS, 65 (11), 1626-1630. http://dx.doi.org/10.1007/ s00018-008-7536-1
19. Danovaro, R., Dell'Anno, A., Pusceddu, A., Gambi, C., Heiner, I., Kristensen, R. M. (2010). The fi rst metazoa living in permanently anoxic conditions. BMC Biology, 8 (1), 30. http://dx.doi.org/10.1186/1741-7007-8-30
20. Darr, D., Fridovich, I. (1995). Adaptation to oxidative stress in young, but not in mature or old, Caenorhabditis elegans. Free Radical Biology and Medicine, 18 (2), 195-201. http://dx.doi.org/10.1016/0891-5849(94)00118-4
21. Davy, P., Allsopp, R. (2011). Hypoxia: Are stem cells in it for the long run? Cell Cycle (Georgetown, Tex.), 10 (2), 206-211.
22. Dawson, T. L., Gores, G. J., Nieminen, A. L., Herman, B., Lemasters, J. J. (1993). Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes. The American Journal of Physiology, 264 (4, Pt. 1), C961-967.
23. Debonneuil, E. H., Quillard, J., Baulieu, E.-E. (2006). Hypoxia and dehydroepiandrosterone in old age: A mouse survival study. Respiratory Research, 7, 144. http:// dx.doi.org/10.1186/1465-9921-7-144
24. Demidenko, Z. N., Blagosklonny, M. V. (2011). The purpose of the HIF-1/PHD feedback loop: To limit mTOR-induced HIF-1 α Cell Cycle (Georgetown, Tex.), 10 (10), 1557-1562.
25. Dhalla, N. S., Elmoselhi, A. B., Hata, T., Makino, N. (2000). Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovascular Research, 47 (3), 446-456. http://dx.doi.org/10.1016/S0008-6363(00)00078-X
26. Dioum, E. M., Chen, R., Alexander, M. S., Zhang, Q., Hogg, R. T., Gerard, R. D., Garcia, J. A. (2009). Regulation of hypoxia-inducible Factor 2 α signaling by the stress-responsive deacetylase sirtuin 1. Science, 324 (5932), 1289-1293. http:// dx.doi.org/10.1126/science.1169956
27. Fehrer, C., Brunauer, R., Laschober, G., Unterluggauer, H., Reitinger, S., Kloss, F., Lepperdinger, G. (2007). Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan. Aging Cell, 6 (6), 745-757. http://dx.doi.org/10.1111/j.1474-9726.2007.00336.x
28. Ferguson, M., Sohal, B. H., Forster, M. J., Sohal, R. S. (2007). Effect of long-term caloric restriction on oxygen consumption and body temperature in two different strains of mice. Mechanisms of Ageing and Development, 128 (10), 539-545. http:// dx.doi.org/10.1016/j.mad.2007.07.005
29. Finkel, T., Deng, C.-X., Mostoslavsky, R. (2009). Recent progress in the biology and physiology of sirtuins. Nature, 460 (7255), 587-591. http://dx.doi.org/10.1038/ nature08197
30. Foe, V. E., Alberts, B. M. (1985). Reversible chromosome condensation induced in Drosophila embryos by anoxia: Visualization of interphase nuclear organization. The Journal of Cell Biology, 100 (5), 1623-1636.
31. Forman, H. J., Maiorino, M., Ursini, F. (2010). Signaling functions of reactive oxygen species. Biochemistry, 49 (5), 835-842. http://dx.doi.org/10.1021/ bi9020378
32. Gharbi, H., Fabretti, F., Bharill, P., Rinschen, M. M., Brinkkötter, S., Frommolt, P., Müller, R.-U. (2013). Loss of the Birt-Hogg-Dubé gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner. Aging Cell, 12 (4), 593-603. http://dx.doi.org/10.1111/acel.12081
33. Gouspillou, G., Hepple, R. T. (2013). Facts and controversies in our understanding of how caloric restriction impacts the mitochondrion. Experimental Gerontology, 48 (10), 1075-1084. http://dx.doi.org/10.1016/j.exger.2013.03.004
34. Grandison, R. C., Wong, R., Bass, T. M., Partridge, L., Piper, M. D. W. (2009). Effect of a standardised dietary restriction protocol on multiple laboratory strains of Drosophila melanogaster. PloS One, 4 (1), e4067. http://dx.doi.org/10.1371/journal.pone.0004067
35. Greer, E. L., Brunet, A. (2009). Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell, 8 (2), 113-127. http://dx.doi.org/10.1111/j.1474-9726.2009.00459.x
36. Guzy, R. D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfi eld, K. D., Schumacker, P. T. (2005). Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metabolism, 1 (6), 401-408. http://dx.doi.org/10.1016/j.cmet.2005.05.001
37. Hagen, T. (2012). Oxygen versus reactive oxygen in the regulation of HIF-1 α: The balance tips. Biochemistry Research International, 2012, 436981. http://dx.doi.org/10.1155/2012/436981
38. Haigis, M. C., Deng, C.-X., Finley, L. W. S., Kim, H.-S., Gius, D. (2012). SIRT3 is a mitochondrial tumor suppressor: A scientifi c tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis. Cancer Research, 72 (10), 2468-2472. http://dx.doi.org/10.1158/0008-5472.CAN-11-3633
39. Hancock, C. R., Han, D.-H., Higashida, K., Kim, S. H., Holloszy, J. O. (2011). Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB Journal: Offi cial Publication of the Federation of American Societies for Experimental Biology, 25 (2), 785-791. http://dx.doi.org/10.1096/fj.10-170415
40. Harada, H., Itasaka, S., Kizaka-Kondoh, S., Shibuya, K., Morinibu, A., Shinomiya, K., Hiraoka, M. (2009). The Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose- and reoxygenation-dependent manner in irradiated tumors. The Journal of Biological Chemistry, 284 (8), 5332-5342. http://dx.doi.org/10.1074/ jbc.M806653200
41. Harman, D. (1956). Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology, 11 (3), 298-300.
42. Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Miller, R. A. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 460 (7253), 392-395. http://dx.doi.org/10.1038/nature08221
43. Hempenstall, S., Page, M. M., Wallen, K. R., Selman, C. (2012). Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice. Mechanisms of Ageing and Development, 133 (1), 37-45. http:// dx.doi.org/10.1016/j.mad.2011.12.002
44. Hochachka, P. W., Somero, G. N. (2002). Biochemical adaptation: Mechanism and process in physiological evolution (1st ed.). New York, NY: Oxford University Press. Holland, H. D. (2006). The oxygenation of the atmosphere and oceans. Philosophical Transactions of the Royal Society B: Biological Sciences, 361 (1470), 903-915. http:// dx.doi.org/10.1098/rstb.2006.1838
45. Honda, S., Ishii, N., Suzuki, K., Matsuo, M. (1993). Oxygen-dependent perturbation of life span and aging rate in the nematode. Journal of Gerontology, 48 (2), B57-B61.
46. Honda, Y., Honda, S. (2001). Life span extensions associated with upregulation of gene expression of antioxidant enzymes in Caenorhabdms elegans; studies of mutation in the AGE-1, PI3 kinase homologue and short-term exposure to hyperoxia. Journal of the American Aging Association, 24 (4), 179-186. http://dx.doi.org/10.1007/s11357-001-0019-z
47. Honda, Y., Tanaka, M., Honda, S. (2008). Modulation of longevity and diapause by redox regulation mechanisms under the insulin-like signaling control in Caenorhabditis elegans. Experimental Gerontology, 43 (6), 520-529. http://dx.doi.org/10.1016/j.exger.2008.02.009
48. Houthoofd, K., Braeckman, B. P., Lenaerts, I., Brys, K., De Vreese, A., Van Eygen, S., Vanfleteren, J. R. (2002a). Axenic growth up-regulates mass-specifi c metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans. Experimental Gerontology, 37 (12), 1371-1378. http://dx.doi.org/10.1016/ S0531-5565(02)00173-0
49. Houthoofd, K., Braeckman, B. P., Lenaerts, I., Brys, K., De Vreese, A., Van Eygen, S., Vanfleteren, J. R. (2002b). No reduction of metabolic rate in food restricted Caenorhabditis elegans. Experimental Gerontology, 37 (12), 1359-1369. http:// dx.doi.org/10.1016/S0531-5565(02)00172-9
50. Houtkooper, R. H., Pirinen, E., Auwerx, J. (2012). Sirtuins as regulators of metabolism and healthspan. Nature Reviews. Molecular Cell Biology, 13 (4), 225-238. http:// dx.doi.org/10.1038/nrm3293
51. Hudson, C. C., Liu, M., Chiang, G. G., Otterness, D. M., Loomis, D. C., Kaper, F., Abraham, R. T. (2002). Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Molecular and Cellular Biology, 22 (20), 7004-7014.
52. Hulbert, A., Clancy, D. J., Mair, W., Braeckman, B. P., Gems, D., Partridge, L. (2004). Metabolic rate is not reduced by dietary-restriction or by lowered insulin/IGF-1 signalling and is not correlated with individual lifespan in Drosophila melanogaster. Experimental Gerontology, 39 (8), 1137-1143. http://dx.doi.org/10.1016/ j.exger.2004.04.006
53. Hunt, N. D., Hyun, D.-H., Allard, J. S., Minor, R. K., Mattson, M. P., Ingram, D. K., de Cabo, R. (2006). Bioenergetics of aging and calorie restriction. Ageing Research Reviews, 5 (2), 125-143. http://dx.doi.org/10.1016/j.arr.2006.03.006
54. Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Semenza, G. L. (1998). Cellular and developmental control of O2 homeostasis by hypoxiainducible factor 1 alpha. Genes & Development, 12 (2), 149-162.
55. Ja, W. W., Carvalho, G. B., Zid, B. M., Mak, E. M., Brummel, T., Benzer, S. (2009). Water- and nutrient-dependent effects of dietary restriction on Drosophila lifespan. Proceedings of the National Academy of Sciences of the United States of America, 106 (44), 18633-18637. http://dx.doi.org/10.1073/pnas.0908016106
56. Jackson, M. J., Pye, D., Palomero, J. (2007). The production of reactive oxygen and nitrogen species by skeletal muscle. Journal of Applied Physiology, 102 (4), 1664-1670. http://dx.doi.org/10.1152/japplphysiol.01102.2006
57. Jamieson, D. (1989). Oxygen toxicity and reactive oxygen metabolites in mammals. Free Radical Biology and Medicine, 7 (1), 87-108. http://dx.doi.org/10.1016/0891-5849(89)90103-2
58. Jeong, J.-K., Seo, J.-S., Moon, M.-H., Lee, Y.-J., Seol, J.-W., Park, S.-Y. (2012). Hypoxiainducible factor-1 alpha regulates prion protein expression to protect against neuron cell damage. Neurobiology of Aging, 33 (5), 1006.e1-1006.e10. http://dx.doi.org/10.1016/j.neurobiolaging.2011.09.037
59. Jia, K., Chen, D., Riddle, D. L. (2004). The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development (Cambridge, England), 131 (16), 3897-3906. http://dx.doi.org/10.1242/dev.01255
60. Jiang, C., Qu, A., Matsubara, T., Chanturiya, T., Jou, W., Gavrilova, O., Gonzalez, F. J. (2011). Disruption of hypoxia-inducible factor 1 in adipocytes improves insulin sensitivity and decreases adiposity in high-fat diet-fed mice. Diabetes, 60 (10), 2484-2495. http://dx.doi.org/10.2337/db11-0174
61. Jiang, H., Guo, R., Powell-Coffman, J. A. (2001). The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proceedings of the National Academy of Sciences, 98 (14), 7916-7921. http://dx.doi.org/10.1073/pnas.141234698
62. Johannsen, D. L., Knuth, N. D., Huizenga, R., Rood, J. C., Ravussin, E., Hall, K. D. (2012). Metabolic slowing with massive weight loss despite preservation of fatfree mass. The Journal of Clinical Endocrinology and Metabolism, 97 (7), 2489-2496. http://dx.doi.org/10.1210/jc.2012-1444
63. Johnson, S. C., Rabinovitch, P. S., Kaeberlein, M. (2013). mTOR is a key modulator of ageing and age-related disease. Nature, 493 (7432), 338-345. http://dx.doi.org/10.1038/nature11861
64. Kaeberlein, M. (2010). Resveratrol and rapamycin: Are they anti-aging drugs? BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology, 32 (2), 96-99. http://dx.doi.org/10.1002/bies.200900171
65. Kaeberlein, M., Hu, D., Kerr, E. O., Tsuchiya, M., Westman, E. A., Dang, N., Kennedy, B. K. (2005). Increased life span due to calorie restriction in respiratory- defi cient yeast. PLoS Genetics, 1 (5), e69. http://dx.doi.org/10.1371/journal.pgen.0010069
66. Kaeberlein, M., Kapahi, P. (2009). The hypoxic response and aging. Cell Cycle (Georgetown, Tex.), 8 (15), 2324.
67. Kaeberlein, M., Kirkland, K. T., Fields, S., Kennedy, B. K. (2004). SIR2-independent life span extension by calorie restriction in yeast. PLoS Biology, 2 (9), E296. http:// dx.doi.org/10.1371/journal.pbio.0020296
68. Kaeberlein, M., McVey, M., Guarente, L. (1999). The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes & Development, 13 (19), 2570-2580.
69. Kaeberlein, M., Powers, R. W., III, Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kennedy, B. K. (2005). Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science (New York, N.Y.), 310 (5751), 1193-1196. http:// dx.doi.org/10.1126/science.1115535
70. Kaeberlein, T. L., Smith, E. D., Tsuchiya, M., Welton, K. L., Thomas, J. H., Fields, S., Kaeberlein, M. (2006). Lifespan extension in Caenorhabditis elegans by complete removal of food. Aging Cell, 5 (6), 487-494. http://dx.doi.org/10.1111/j.1474-9726.2006.00238.x
71. Kaelin, W. G., Jr. (2002). How oxygen makes its presence felt. Genes & Development, 16 (12), 1441-1445. http://dx.doi.org/10.1101/gad.1003602
72. Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., Cohen, H. Y. (2012). The sirtuin SIRT6 regulates lifespan in male mice. Nature, 483 (7388), 218-221. http://dx.doi.org/10.1038/nature10815
73. Kang, M. J., Kim, H. J., Kim, H. K., Lee, J. Y., Kim, D. H., Jung, K. J., Chung, H. Y. (2005). The effect of age and calorie restriction on HIF-1-responsive genes in aged liver. Biogerontology, 6 (1), 27-37. http://dx.doi.org/10.1007/ s10522-004-7381-z
74. Kapahi, P., Chen, D., Rogers, A. N., Katewa, S. D., Li, P. W.-L., Thomas, E. L., Kockel, L. (2010). With TOR, less is more: A key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metabolism, 11 (6), 453-465. http://dx.doi.org/10.1016/ j.cmet.2010.05.001
75. Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., Benzer, S. (2004). Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Current Biology: CB, 14 (10), 885-890. http://dx.doi.org/10.1016/ j.cub.2004.03.059
76. Kennedy, B. K., Steffen, K. K., Kaeberlein, M. (2007). Ruminations on dietary restriction and aging. Cellular and Molecular Life Sciences: CMLS, 64 (11), 1323-1328. http://dx.doi.org/10.1007/s00018-007-6470-y
77. Kenyon, C., Chang, J., Gensch, E., Rudner, A., Tabtiang, R. (1993). A C. elegans mutant that lives twice as long as wild type. Nature, 366 (6454), 461-464. http://dx.doi.org/10.1038/366461a0
78. Kim, H. J., Jung, K. J., Yu, B. P., Cho, C. G., Choi, J. S., Chung, H. Y. (2002). Modulation of redox-sensitive transcription factors by calorie restriction during aging. Mechanisms of Ageing and Development, 123 (12), 1589-1595. http://dx.doi.org/10.1016/S0047-6374(02)00094-5
79. Kim, W., Kaelin, W. G., Jr. (2003). The von Hippel-Lindau tumor suppressor protein: New insights into oxygen sensing and cancer. Current Opinion in Genetics & Development, 13 (1), 55-60.
80. Kimura, K. D., Tissenbaum, H. A., Liu, Y., Ruvkun, G. (1997). daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science (New York, N.Y.), 277 (5328), 942-946.
81. Kirienko, N. V., Kirienko, D. R., Larkins-Ford, J., Wählby, C., Ruvkun, G., Ausubel, F. M. (2013). Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death. Cell Host & Microbe, 13 (4), 406-416. http://dx.doi.org/10.1016/j.chom.2013.03.003
82. Kirito, K., Hu, Y., Komatsu, N. (2009). HIF-1 prevents the overproduction of mitochondrial ROS after cytokine stimulation through induction of PDK-1. Cell Cycle (Georgetown, Tex.), 8 (17), 2844-2849.
83. Koc, A., Gasch, A. P., Rutherford, J. C., Kim, H.-Y., Gladyshev, V. N. (2004). Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen speciesdependent and -independent components of aging. Proceedings of the National Academy of Sciences of the United States of America, 101 (21), 7999-8004. http:// dx.doi.org/10.1073/pnas.0307929101
84. Lanza, I. R., Zabielski, P., Klaus, K. A., Morse, D. M., Heppelmann, C. J., Bergen, H. R., III, Nair, K. S. (2012). Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis. Cell Metabolism, 16 (6), 777-788. http://dx.doi.org/10.1016/j.cmet.2012.11.003
85. Larsen, P. L., Albert, P. S., Riddle, D. L. (1995). Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics, 139 (4), 1567-1583.
86. Lee, G. D., Wilson, M. A., Zhu, M., Wolkow, C. A., de Cabo, R., Ingram, D. K., Zou, S. (2006). Dietary deprivation extends lifespan in Caenorhabditis elegans. Aging Cell, 5 (6), 515-524. http://dx.doi.org/10.1111/j.1474-9726.2006.00241.x
87. Lee, S.-J., Hwang, A. B., Kenyon, C. (2010). Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Current Biology: CB, 20 (23), 2131-2136. http://dx.doi.org/10.1016/j.cub.2010.10.057
88. Lefer, D. J., Granger, D. N. (2000). Oxidative stress and cardiac disease. The American Journal of Medicine, 109 (4), 315-323. http://dx.doi.org/10.1016/ S0002-9343(00)00467-8
89. Leiser, S. F., Begun, A., Kaeberlein, M. (2011). HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell, 10 (2), 318-326. http://dx.doi.org/10.1111/j.1474-9726.2011.00672.x
90. Leiser, S. F., Fletcher, M., Begun, A., Kaeberlein, M. (2013). Life-span extension from hypoxia in Caenorhabditis elegans requires both HIF-1 and DAF-16 and is antagonized by SKN-1. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 68 (10), 1135-1144. http://dx.doi.org/10.1093/gerona/glt016
91. Li, M., Kim, W. Y. (2011). Two sides to every story: the HIF-dependent and HIFindependent functions of pVHL. Journal of Cellular and Molecular Medicine, 15 (2), 187-195. http://dx.doi.org/10.1111/j.1582-4934.2010.01238.x
92. Lin, S. J., Defossez, P. A., Guarente, L. (2000). Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science (New York, N.Y.), 289 (5487), 2126-2128.
93. Lin, S. J., Kaeberlein, M., Andalis, A. A., Sturtz, L. A., Defossez, P.-A., Culotta, V. C., Guarente, L. (2002). Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature, 418 (6895), 344-348. http://dx.doi.org/10.1038/ nature00829
94. Liu, T., Cai, D. (2013). Counterbalance between BAG and URX neurons via guanylate cyclases controls lifespan homeostasis in C. elegans. The EMBO Journal, 32 (11), 1529-1542. http://dx.doi.org/10.1038/emboj.2013.75
95. Loh, K. P., Huang, S. H., De Silva, R., Tan, B. K. H., Zhu, Y. Z. (2006). Oxidative stress: Apoptosis in neuronal injury. Current Alzheimer Research, 3 (4), 327-337.
96. Longo, V. D., Shadel, G. S., Kaeberlein, M., Kennedy, B. (2012). Replicative and chronological aging in Saccharomyces cerevisiae. Cell Metabolism, 16 (1), 18-31. http:// dx.doi.org/10.1016/j.cmet.2012.06.002
97. Mair, W., Dillin, A. (2008). Aging and survival: The genetics of life span extension by dietary restriction. Annual Review of Biochemistry, 77, 727-754. http://dx.doi.org/10.1146/annurev.biochem.77.061206.171059
98. Mannello, F., Medda, V., Tonti, G. A. (2011). Hypoxia and neural stem cells: From invertebrates to brain cancer stem cells. The International Journal of Developmental Biology, 55 (6), 569-581. http://dx.doi.org/10.1387/ijdb.103186fm
99. Mansfi eld, K. D., Guzy, R. D., Pan, Y., Young, R. M., Cash, T. P., Schumacker, P. T., Simon, M. C. (2005). Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metabolism, 1 (6), 393-399. http://dx.doi.org/10.1016/j.cmet.2005.05.003
100. Martin, C. K., Heilbronn, L. K., de Jonge, L., DeLany, J. P., Volaufova, J., Anton, S. D., Ravussin, E. (2007). Effect of calorie restriction on resting metabolic rate and spontaneous physical activity. Obesity (Silver Spring, Md.), 15 (12), 2964-2973. http:// dx.doi.org/10.1038/oby.2007.354
101. Masoro, E. J. (2005). Overview of caloric restriction and ageing. Mechanisms of Ageing and Development, 126 (9), 913-922. http://dx.doi.org/10.1016/j.mad.2005.03.012
102. McDonough, M. A., Li, V., Flashman, E., Chowdhury, R., Mohr, C., Liénard, B. M. R., Schofi eld, C. J. (2006). Cellular oxygen sensing: Crystal structure of hypoxiainducible factor prolyl hydroxylase (PHD2). Proceedings of the National Academy of Sciences of the United States of America, 103 (26), 9814-9819. http://dx.doi.org/10.1073/pnas.0601283103
103. McInturff, A. M., Cody, M. J., Elliott, E. A., Glenn, J. W., Rowley, J. W., Rondina, M. T., Yost, C. C. (2012). Mammalian target of rapamycin regulates neutrophil extracellular trap formation via induction of hypoxia-inducible factor 1 α Blood, 120 (15), 3118-3125. http://dx.doi.org/10.1182/blood-2012-01-405993
104. McNeill, L. A., Flashman, E., Buck, M. R. G., Hewitson, K. S., Clifton, I. J., Jeschke, G., Schofi eld, C. J. (2005). Hypoxia-inducible factor prolyl hydroxylase 2 has a high affi nity for ferrous iron and 2-oxoglutarate. Molecular BioSystems, 1 (4), 321-324. http://dx.doi.org/10.1039/b511249b
105. Mehta, R., Steinkraus, K. A., Sutphin, G. L., Ramos, F. J., Shamieh, L. S., Huh, A., Kaeberlein, M. (2009). Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science, 324 (5931), 1196-1198. http://dx.doi.org/10.1126/ science.1173507
106. Mendenhall, A. R., LaRue, B., Padilla, P. A. (2006). Glyceraldehyde-3-phosphate dehydrogenase mediates anoxia response and survival in Caenorhabditis elegans. Genetics, 174 (3), 1173-1187. http://dx.doi.org/10.1534/genetics.106.061390
107. Miller, B. F., Robinson, M. M., Bruss, M. D., Hellerstein, M., Hamilton, K. L. (2012). A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction. Aging Cell, 11 (1), 150-161. http:// dx.doi.org/10.1111/j.1474-9726.2011.00769.x
108. Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., de Cabo, R., Strong, R. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 66 (2), 191-201. http://dx.doi.org/10.1093/gerona/ glq178
109. Mockett, R. J., Sohal, R. S., Orr, W. C. (1999). Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia. FASEB Journal: Offi cial Publication of the Federation of American Societies for Experimental Biology, 13 (13), 1733-1742.
110. Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Alt, F. W. (2006). Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell, 124 (2), 315-329. http://dx.doi.org/10.1016/ j.cell.2005.11.044
111. Müller, R.-U., Fabretti, F., Zank, S., Burst, V., Benzing, T., Schermer, B. (2009). The von Hippel Lindau tumor suppressor limits longevity. Journal of the American Society of Nephrology: JASN, 20 (12), 2513-2517. http://dx.doi.org/10.1681/ ASN.2009050497
112. Murakami, C. J., Burtner, C. R., Kennedy, B. K., Kaeberlein, M. (2008). A method for high-throughput quantitative analysis of yeast chronological life span. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 63 (2), 113-121.
113. Murakami, C. J., Wall, V., Basisty, N., Kaeberlein, M. (2011). Composition and acidifi - cation of the culture medium infl uences chronological aging similarly in vineyard and laboratory yeast. PloS One, 6 (9), e24530. http://dx.doi.org/10.1371/journal.pone.0024530
114. Ogunshola, O. O., Antoniou, X. (2009). Contribution of hypoxia to Alzheimer's disease: Is HIF-1alpha a mediator of neurodegeneration? Cellular and Molecular Life Sciences: CMLS, 66 (22), 3555-3563. http://dx.doi.org/10.1007/s00018-009-0141-0
115. Packer, L., Fuehr, K. (1977). Low oxygen concentration extends the lifespan of cultured human diploid cells. Nature, 267 (5610), 423-425.
116. Pearl, R. (1928). The rate of living: Being an account of some experimental studies on the biology of life duration New York, NY: A.A. Knopf.
117. Powers, R. W., III, Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., Fields, S. (2006). Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes & Development, 20 (2), 174-184. http://dx.doi.org/10.1101/gad.1381406
118. Putker, M., Madl, T., Vos, H. R., de Ruiter, H., Visscher, M., van den Berg, M. C. W., Dansen, T. B. (2013). Redox-dependent control of FOXO/DAF-16 by transportin-1. Molecular Cell, 49 (4), 730-742. http://dx.doi.org/10.1016/j.molcel.2012.12.014
119. Rabie, T., Kunze, R., Marti, H. H. (2011). Impaired hypoxic response in senescent mouse brain. International Journal of Developmental Neuroscience: The Offi cial Journal of the International Society for Developmental Neuroscience, 29 (6), 655-661. http:// dx.doi.org/10.1016/j.ijdevneu.2011.06.003
120. Ramsey, J. J., Hagopian, K. (2006). Energy expenditure and restriction of energy intake: Could energy restriction alter energy expenditure in companion animals? The Journal of Nutrition, 136 (7 Suppl.), 1958S-1966S.
121. Rascón, B., Harrison, J. F. (2010). Lifespan and oxidative stress show a non-linear response to atmospheric oxygen in Drosophila. The Journal of Experimental Biology, 213 (Pt. 20), 3441-3448. http://dx.doi.org/10.1242/jeb.044867
122. Rea, S. L., Ventura, N., Johnson, T. E. (2007). Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biology, 5 (10), e259. http://dx.doi.org/10.1371/ journal.pbio.0050259
123. Redman, L. M., Heilbronn, L. K., Martin, C. K., de Jonge, L., Williamson, D. A., Delany, J. P., Pennington CALERIE Team. (2009). Metabolic and behavioral compensations in response to caloric restriction: Implications for the maintenance of weight loss. PloS One, 4 (2), e4377. http://dx.doi.org/10.1371/journal.pone.0004377
124. Rey, S., Luo, W., Shimoda, L. A., Semenza, G. L. (2011). Metabolic reprogramming by HIF-1 promotes the survival of bone marrow-derived angiogenic cells in ischemic tissue. Blood, 117 (18), 4988-4998. http://dx.doi.org/10.1182/ blood-2010-11-321190
125. Rezvani, H. R., Ali, N., Nissen, L. J., Harfouche, G., de Verneuil, H., Taïeb, A., Mazurier, F. (2011). HIF-1 α in epidermis: Oxygen sensing, cutaneous angiogenesis, cancer, and non-cancer disorders. Journal of Investigative Dermatology, 131 (9), 1793-1805. http://dx.doi.org/10.1038/jid.2011.141
126. Rogina, B., Helfand, S. L. (2004). SIR2 mediates longevity in the fl y through a pathway related to calorie restriction. Proceedings of the National Academy of Sciences of the United States of America, 101 (45), 15998-16003. http://dx.doi.org/10.1073/ pnas.0404184101
127. Roitbak, T., Surviladze, Z., Cunningham, L. A. (2011). Continuous expression of HIF-1 α in neural stem/progenitor cells. Cellular and Molecular Neurobiology, 31 (1), 119-133. http://dx.doi.org/10.1007/s10571-010-9561-5
128. Schofi eld, C. J., Ratcliffe, P. J. (2004). Oxygen sensing by HIF hydroxylases. Nature Reviews. Molecular Cell Biology, 5 (5), 343-354. http://dx.doi.org/10.1038/nrm1366
129. Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., Ristow, M. (2007). Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metabolism, 6 (4), 280-293. http:// dx.doi.org/10.1016/j.cmet.2007.08.011
130. Scott, B. A., Avidan, M. S., Crowder, C. M. (2002). Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2. Science (New York, N.Y.), 296 (5577), 2388-2391. http://dx.doi.org/10.1126/science.1072302
131. Selman, C., Phillips, T., Staib, J. L., Duncan, J. S., Leeuwenburgh, C., Speakman, J. R. (2005). Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition. Mechanisms of Ageing and Development, 126 (6-7), 783-793. http://dx.doi.org/10.1016/j.mad.2005.02.004
132. Semenza, G. (2002). Signal transduction to hypoxia-inducible factor 1. Biochemical Pharmacology, 64 (5-6), 993-998.
133. Semenza, G. L. (2009). Regulation of vascularization by hypoxia-inducible factor 1. Annals of the New York Academy of Sciences, 1177, 2-8. http://dx.doi.org/10.1111/j.1749-6632.2009.05032.x
134. Severinghaus, J. W. (2002). Priestley, the furious free thinker of the enlightenment, and Scheele, the taciturn apothecary of Uppsala. Acta Anaesthesiologica Scandinavica, 46 (1), 2-9. http://dx.doi.org/10.1046/j.0001-5172.2001.00351.x
135. Shao, Z., Zhang, Y., Powell-Coffman, J. A. (2009). Two distinct roles for EGL-9 in the regulation of HIF-1-mediated gene expression in Caenorhabditis elegans. Genetics, 183 (3), 821-829. http://dx.doi.org/10.1534/genetics.109.107284
136. Sharp, Z. D. (2011). Aging and TOR: Interwoven in the fabric of life. Cellular and Molecular Life Sciences: CMLS, 68 (4), 587-597. http://dx.doi.org/10.1007/s00018-010-0542-0
137. Shen, C., Nettleton, D., Jiang, M., Kim, S. K., Powell-Coffman, J. A. (2005). Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans. The Journal of Biological Chemistry, 280 (21), 20580-20588. http://dx.doi.org/10.1074/jbc.M501894200
138. Shen, C., Powell-Coffman, J. A. (2003). Genetic analysis of hypoxia signaling and response in C elegans. Annals of the New York Academy of Sciences, 995, 191-199.
139. Shen, C., Shao, Z., Powell-Coffman, J. A. (2006). The Caenorhabditis elegans rhy-1 gene inhibits HIF-1 hypoxia-inducible factor activity in a negative feedback loop that does not include vhl-1. Genetics, 174 (3), 1205-1214. http://dx.doi.org/10.1534/ genetics.106.063594
140. Skorupa, D. A., Dervisefendic, A., Zwiener, J., Pletcher, S. D. (2008). Dietary composition specifi es consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell, 7 (4), 478-490. http://dx.doi.org/10.1111/j.1474-9726.2008.00400.x
141. Smith, D. L., Jr, McClure, J. M., Matecic, M., Smith, J. S. (2007). Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins. Aging Cell, 6 (5), 649-662. http://dx.doi.org/10.1111/j.1474-9726.2007.00326.x
142. Smith, E. D., Kaeberlein, T. L., Lydum, B. T., Sager, J., Welton, K. L., Kennedy, B. K., Kaeberlein, M. (2008). Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans. BMC Developmental Biology, 8, 49. http://dx.doi.org/10.1186/1471-213X-8-49
143. Sohal, R. S., Agarwal, S., Dubey, A., Orr, W. C. (1993). Protein oxidative damage is associated with life expectancy of housefl ies. Proceedings of the National Academy of Sciences of the United States of America, 90 (15), 7255-7259.
144. Sohal, R. S., Orr, W. C. (2012). The redox stress hypothesis of aging. Free Radical Biology & Medicine, 52 (3), 539-555. http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.445
145. Speakman, J. R. (2005). Body size, energy metabolism and lifespan. Journal of Experimental Biology, 208 (Pt. 9), 1717-1730. http://dx.doi.org/10.1242/jeb.01556
146. Stanfel, M. N., Shamieh, L. S., Kaeberlein, M., Kennedy, B. K. (2009). The TOR pathway comes of age. Biochimica et Biophysica Acta, 1790 (10), 1067-1074. http:// dx.doi.org/10.1016/j.bbagen.2009.06.007
147. Sung, H. J., Ma, W., Starost, M. F., Lago, C. U., Lim, P. K., Sack, M. N., Hwang, P. M. (2011). Ambient oxygen promotes tumorigenesis. PLoS One, 6 (5), e19785. http:// dx.doi.org/10.1371/journal.pone.0019785
148. Sutphin, G. L., Kaeberlein, M. (2008). Dietary restriction by bacterial deprivation increases life span in wild-derived nematodes. Experimental Gerontology, 43 (3), 130-135. http://dx.doi.org/10.1016/j.exger.2007.10.019
149. Takubo, K., Goda, N., Yamada, W., Iriuchishima, H., Ikeda, E., Kubota, Y., Suda, T. (2010). Regulation of the HIF-1 α level is essential for hematopoietic stem cells. Cell Stem Cell, 7 (3), 391-402. http://dx.doi.org/10.1016/j.stem.2010.06.020
150. Tan, T., Marín-García, J., Damle, S., Weiss, H. R. (2010). Hypoxia-inducible factor-1 improves inotropic responses of cardiac myocytes in ageing heart without affecting mitochondrial activity. Experimental Physiology, 95 (6), 712-722. http://dx.doi.org/10.1113/expphysiol.2009.051649
151. Tatar, M. (2011). The plate half-full: Status of research on the mechanisms of dietary restriction in Drosophila melanogaster. Experimental Gerontology, 46 (5), 363-368. http://dx.doi.org/10.1016/j.exger.2010.12.002
152. Tissenbaum, H. A., Guarente, L. (2001). Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature, 410 (6825), 227-230. http://dx.doi.org/ 10.1038/35065638
153. Tormos, K. V., Chandel, N. S. (2010). Inter-connection between mitochondria and HIFs. Journal of Cellular and Molecular Medicine, 14 (4), 795-804. http://dx.doi.org/ 10.1111/j.1582-4934.2010.01031.x
154. Turrens, J. F. (2003). Mitochondrial formation of reactive oxygen species. The Journal of Physiology, 552 (2), 335-344. http://dx.doi.org/10.1113/jphysiol.2003.049478
155. Underwood, E. A. (1944). Lavoisier and the History of Respiration. Proceedings of the Royal Society of Medicine, 37 (6), 247-262.
156. Van de Velde, S., Hogan, M. F., Montminy, M. (2011). mTOR links incretin signaling to HIF induction in pancreatic beta cells. Proceedings of the National Academy of Sciences of the United States of America, 108 (41), 16876-16882. http://dx.doi.org/ 10.1073/pnas.1114228108
157. Van Voorhies, W. A. (2002). The infl uence of metabolic rate on longevity in the nematode Caenorhabditis elegans. Aging Cell, 1 (2), 91-101. http://dx.doi.org/10.1046/ j.1474-9728.2002.00022.x
158. Van Voorhies, W. A. (2004). Live fast-live long? A commentary on a recent paper by Speakman et al. Aging Cell, 3 (5), 327-330. http://dx.doi.org/10.1111/j.1474-9728.2004.00113.x
159. Van Voorhies, W. A. (2009). Metabolic function in Drosophila melanogaster in response to hypoxia and pure oxygen. The Journal of Experimental Biology, 212 (19), 3132-3141. http://dx.doi.org/10.1242/jeb.031179
160. Van Voorhies, W. A., Ward, S. (1999). Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proceedings of the National Academy of Sciences of the United States of America, 96 (20), 11399-11403.
161. Van Voorhies, W. A., Ward, S. (2000). Broad oxygen tolerance in the nematode Caenorhabditis elegans. The Journal of Experimental Biology, 203 (Pt. 16), 2467-2478.
162. Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., Müller, F. (2003). Genetics: Infl uence of TOR kinase on lifespan in C. elegans. Nature, 426 (6967), 620. http://dx.doi.org/10.1038/426620a
163. Vigne, P., Frelin, C. (2006). A low protein diet increases the hypoxic tolerance in Drosophila. PLoS One, 1 (1), e56. http://dx.doi.org/10.1371/journal.pone.0000056
164. Waalen, J., Buxbaum, J. N. (2011). Is older colder or colder older? The association of age with body temperature in 18,630 individuals. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 66 (5), 487-492. http://dx.doi.org/10.1093/gerona/glr001
165. Wang, D., Malo, D., Hekimi, S. (2010). Elevated mitochondrial reactive oxygen species generation affects the immune response via hypoxia-inducible factor-1alpha in long-lived Mclk1 + /- mouse mutants. Journal of Immunology (Baltimore, Md.: 1950), 184 (2), 582-590. http://dx.doi.org/10.4049/jimmunol.0902352
166. Wang, G. L., Jiang, B. H., Rue, E. A., Semenza, G. L. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proceedings of the National Academy of Sciences of the United States of America, 92 (12), 5510-5514.
167. Weinberg, C. R., Brown, K. G., Hoel, D. G. (1987). Altitude, radiation, and mortality from cancer and heart disease. Radiation Research, 112 (2), 381-390.
168. Westerterp-Plantenga, M. S., van Marken Lichtenbelt, W. D., Strobbe, H., Schrauwen, P. (2002). Energy metabolism in humans at a lowered ambient temperature. European Journal of Clinical Nutrition, 56 (4), 288-296. http://dx.doi.org/10.1038/ sj.ejcn.1601308
169. Wikström, M., Krab, K., Saraste, M. (1981). Cytochrome oxidase: A synthesis New York, NY: Academic Press.
170. Yang, W., Hekimi, S. (2010). A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biology, 8 (12), e1000556. http://dx.doi.org/10.1371/journal.pbio.1000556
171. Yee Koh, M., Spivak-Kroizman, T. R., Powis, G. (2008). HIF-1 regulation: Not so easy come, easy go. Trends in Biochemical Sciences, 33 (11), 526-534. http://dx.doi.org/10.1016/j.tibs.2008.08.002
172. Zhang, X., Sarkar, K., Rey, S., Sebastian, R., Andrikopoulou, E., Marti, G. P., Harmon, J. W. (2011). Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds. Journal of Molecular Medicine (Berlin, Germany), 89 (10), 985-995. http://dx.doi.org/10.1007/s00109-011-0754-2
173. Zhang, Y., Shao, Z., Zhai, Z., Shen, C., Powell-Coffman, J. A. (2009). The HIF-1 hypoxia-inducible factor modulates lifespan in C. elegans. PLoS One, 4 (7), e6348. http://dx.doi.org/10.1371/journal.pone.0006348
174. Zheng, H., Lapointe, J., Hekimi, S. (2010). Lifelong protection from global cerebral ischemia and reperfusion in long-lived Mclk1(+/)(-) mutants. Experimental Neurology, 223 (2), 557-565. http://dx.doi.org/10.1016/j.expneurol.2010.02.002
175. Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R. E., Vadysirisack, D. D., Mostoslavsky, R. (2010). The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell, 140 (2), 280-293. http://dx.doi.org/10.1016/j.cell.2009.12.041
176. Zimmer, M., Gray, J. M., Pokala, N., Chang, A. J., Karow, D. S., Marletta, M. A., Bargmann, C. I. (2009). Neurons detect increases and decreases in oxygen levels using distinct guanylate cyclases. Neuron, 61 (6), 865-879. http://dx.doi.org/ 10.1016/j.neuron.2009.02.013