Function and regulation of lipid biology in Caenorhabditis elegans aging

Frontiers in Physiology

Volumn 3 MAY, Issue , 2012, Pages

  Hou, Nicole Shangming ^a,b   Taubert, Stefan ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Ascarosides; C. Elegans; Fatty acids; Lipase; Lipids; Mitochondria; N acylethanolamine; Nuclear hormone receptors

Indexed keywords

EID: 84866365418     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2012.00143     Document Type: Article

References (105)

1. Ackerman, D., and Gems, D. (2012). The mystery of C. elegans aging: an emerging role for fat: distant parallels between C. elegans aging and metabolic syndrome? BioEssays. doi: 10.1002/bies.201100189
2. Antebi, A., Culotti, J. G., and Hedge-cock, E. M. (1998). daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans. Development 125, 1191-1205.
3. Antebi, A., Yeh, W. H., Tait, D., Hedge-cock, E. M., and Riddle, D. L. (2000). daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes Dev. 14,1512-1527.
4. Arantes-Oliveira, N. (2002). Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295, 502-505.
5. Arda, H. E., Taubert, S., Macneil, L. T., Conine, C. C., Tsuda, B., Van Gilst, M., Sequerra, R., Doucette-Stamm, L., Yamamoto, K. R., and Walhout, A. J.M. (2010).Functionalmodular-ity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network. Mol Syst. Biol. 6, 367.
6. Artal-Sanz, M., and Tavernarakis, N. (2009). Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans. Nature 461,793-797.
7. Ashrafi, K., Chang, F. Y., Watts, J. L., Fraser, A. G., Kamath, R. S., Ahringer, J., and Ruvkun, G. (2003). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421,268-272.
8. Bank, E. M., Ben-Harush, K., Wiesel-Motiuk, N., Barkan, R., Feinstein, N., Lotan, O., Medalia, O., and Gruenbaum, Y. (2011). A lamino-pathic mutation disrupting lamin filament assembly causes disease-like phenotypes in Caenorhabditis elegans. Mol. Biol. Cell 22, 2716-2728.
9. Bank, E. M., and Gruenbaum, Y. (2011). Caenorhabditis elegans as a model system for studying the nuclear lamina and laminopathic diseases. Nucleus 2, 350-357.
10. Banni, S., and Di Marzo, V. (2010). Effect of dietary fat on endo-cannabinoids and related mediators: consequences on energy home-ostasis, inflammation and mood. Mol. Nutr. Food Res. 54, 82-92.
11. Branicky, R., Desjardins, D., Liu, J.-L., and Hekimi, S. (2010). Lipid transport and signaling in Caenorhabditis elegans. Dev. Dyn. 239, 1365-1377.
12. Brock, T. J., Browse, J., and Watts, J. L. (2006). Genetic regulation of unsaturated fatty acid composition in C. elegans. PLoS Genet. 2, e108. doi:10.1371/journal.pgen.0020108
13. Brooks, K. K., Liang, B., and Watts, J. L. (2009). The influence of bacterial diet on fat storage in C. elegans. PLoS ONE 4, e7545. doi:10.1371/jour-nal.pone.0007545
14. Budovskaya, Y. V., Wu, K., Southworth, L. K., Jiang, M., Tedesco, P., Johnson, T. E., and Kim, S. K. (2008). An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell 134,291-303.
15. Butcher, R. A., Fujita, M., Schroeder, F. C., and Clardy, J. (2007). Small-molecule pheromones that control dauer development in Caenorhabditis elegans. Nat. Chem. Biol. 3, 420-422.
16. Butcher, R. A., Ragains, J. R., Li, W., Ruvkun, G., Clardy, J., and Mak, H. Y (2009). Biosynthesis of the Caenorhabditis elegans dauer pheromone. Proc. Natl. Acad. Sci. U.S.A. 106, 1875.
17. Chen, S., Whetstine, J. R., Ghosh, S., Hanover, J. A., Gali, R. R., Grosu, P., and Shi, Y. (2009). The conserved NAD (H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span. Proc. Natl. Acad. Sci. U.S.A. 106, 1496.
18. Cristina, D., Cary, M., Lunceford, A., Clarke, C., and Kenyon, C. (2009). A Regulated response to impaired respiration slows behavioral rates and increases lifespan in Caenorhabditis elegans. PLoS Genet. 5, e1000450. doi:10.1371/journal.pgen.1000450
19. De Sandre-Giovannoli, A. (2003). Lamin a truncation in Hutchinson-Gilford progeria. Science 300, 2055-2055.
20. D'Mello, N. P., Childress, A. M., Franklin, D. S., Kale, S. P., Pin-swasdi, C., and Jazwinski, S. M. (1994). Cloning and characterization of LAG1, a longevity-assurance gene in yeast. J. Biol. Chem. 269, 15451-15459.
21. Durieux, J., Wolff, S., and Dillin, A. (2011). The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144, 79-91.
22. Fahy, E., Subramaniam, S., Murphy, R. C., Nishijima, M., Raetz, C. R. H., Shimizu, T., Spener, F., van Meer, G., Wakelam, M. J. O., and Dennis, E. A. (2009). Update of the LIPID MAPS comprehensive classification system for lipids. J. Lipid Res. 50(Suppl.), S9-S14.
23. Feng, J., Bussière, F., and Hekimi, S. (2001). Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev. Cell 1,633-644.
24. Fire, A., Xu, S. Q., Montgomery, M. K., Kostas, S. A., Driver, S. E., and Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811.
25. Fontana, L., Partridge, L., and Longo, V. D. (2010). Extending healthy life span - from yeast to humans. Science 328,321-326.
26. Fu, J., Gaetani, S., Oveisi, F., Lo Verme, J., Serrano, A., Rodríguez De Fonseca, F., Rosengarth, A., Luecke, H., Di Giacomo, B., Tarzia, G., and Piomelli, D. (2003). Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425, 90-93.
27. Fuchs, S., Bundy, J. G., Davies, S. K., Viney, J. M., Swire, J. S., and Leroi, A. M. (2010). A metabolic signature of long life in Caenorhabditis elegans. BMC Biol. 8, 14. doi:10.1186/1741-7007-8-14
28. Gáliková, M., Klepsatel, P., Senti, G., and Flatt, T. (2011). Steroid hormone regulation of C. elegans and Drosophila aging and life history. Exp. Gerontol. 46, 141-147.
29. Gallo, M., and Riddle, D. L. (2010). Regulation of metabolism in Caenorhabditis elegans longevity. J. Biol. 9, 7.
30. Germain, P., Staels, B., Dacquet, C., Spedding, M., and Laudet, V. (2006). Overview of nomenclature of nuclear receptors. Pharmacol Rev. 58, 685-704.
31. Golden, T. R., Hubbard, A., Dando, C., Herren, M. A., and Melov, S. (2008). Age-related behaviors have distinct transcriptional profiles in Caenorhabditis elegans. Aging Cell 7, 850-865.
32. Gonzalez, F. J. (2008). Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription. Drug Metab. Pharmacokinet. 23, 2-7.
33. Goudeau, J., Bellemin, S., Toselli-Mollereau, E., Shamalnasab, M., Chen, Y., and Aguilaniu, H. (2011). Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans. PLoS Biol. 9, e1000599. doi:10.1371/jour-nal.pbio.1000599
34. Gruber, J., Ng, L. F., Fong, S., Wong, Y. T., Koh, S. A., Chen, C.-B., Shui, G., Cheong, W. F., Schaffer, S., Wenk, M. R., and Halliwell, B. (2011). Mitochondrial changes in ageing Caenorhabditis elegans - what do we learn from superoxide dismutase knockouts? PLoS ONE 6, e19444. doi:10.1371/journal.pone.0019444
35. Guillas, I., Kirchman, P. A., Chuard, R., Pfefferli, M., Jiang, J. C., Jazwinski, S. M., and Conzelmann, A. (2001). C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p. EMBO J.20,2655-2665.
36. Halaschek-Wiener, J., Khattra, J. S., McKay, S., Pouzyrev, A., Stott, J. M., Yang, G. S., Holt, R. A., Jones, S. J. M., Marra, M. A., Brooks-Wilson, A. R., and Riddle, D. L. (2005). Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res. 15, 603-615.
37. Hansen, M., Chandra, A., Mitic, L. L., Onken, B., Driscoll, M., and Kenyon, C. (2008). A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet. 4, e24.doi:10.1371/jour-nal.pgen.0040024
38. Hansen, M., Hsu, A.-L., Dillin, A., and Kenyon, C. (2005). New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet. 1, e17. doi:10.1371/journal.pgen.0010017
39. Hansen, M., Taubert, S., Crawford, D., Libina, N., Lee, S.-J., and Kenyon, C. (2007). Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6, 95-110.
40. Harman, D. (1956). Aging: a theory based on free radical and radiation chemistry.J. Gerontol. 11,298-300.
41. Hekimi, S., Lapointe, J., and Wen, Y. (2011). Taking a "good" look at free radicals in the aging process. Trends Cell Biol. 21, 569-576.
42. Henis-Korenblit, S., Zhang, P., Hansen, M., McCormick, M., Lee, S.-J., Cary, M., and Kenyon, C. (2010). Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc. Natl. Acad. Sci. U.S.A. 107, 9730-9735.
43. Hertz, R., Ben-Haim, N., Petrescu, A. D., Kalderon, B., Berman, I., Eldad, N., Schroeder, F., and Bar-Tana, J. (2003). Rescue of MODY-1 by agonist ligands of hepatocyte nuclear factor-4alpha. J. Biol. Chem. 278, 22578-22585.
44. Hillyard, S. L., and German, J. B. (2009). Quantitative lipid analysis and life span of the fat-3 mutant of Caenorhabditis elegans. J. Agric. Food Chem. 57,3389-3396.
45. Hsin, H., and Kenyon, C. (1999). Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366.
46. Hu,P. J. (2007).Dauer. WormBook 1-19.
47. Hulbert,A. (2011). Longevity, lipids and C. elegans. Aging (Albany N. Y.)3,81.
48. Iser, W. B., Kim, D., Bachman, E., and Wolkow, C. (2005). Examination of the requirement for ucp-4, a putative homologof mammalian uncoupling proteins, for stress tolerance and longevity in C. elegans. Mech. Ageing Dev. 126,1090-1096.
49. Jeong, P.-Y., Jung, M., Yim, Y.-H., Kim, H., Park, M., Hong, E., Lee, W., Kim, Y.H.,Kim,K.,andPaik,Y.-K. (2005). Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone. Nature 433, 541-545.
50. Joo, H. J., Kim, K. Y., Yim, Y H., Jin, Y X., Kim, H., Kim, M. Y., and Paik, Y K. (2010). Contribution of the peroxisomal acox gene to the dynamic balance of daumone production in Caenorhabditis elegans. J. Biol Chem. 285,29319-29325.
51. Joo, H. J., Yim, Y.-H., Jeong, P.-Y., Jin, Y X., Lee, J. E., Kim, H., Jeong, S. K., Chitwood, D. J., and Paik, Y.-K. (2009). Caenorhabditis elegansutilizes dauer pheromone biosynthesis to dispose of toxic peroxisomal fatty acids for cellular homoeostasis. Biochem. J. 422, 61-71.
52. Kenyon, C. (2010a). The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing. Proc. R. Soc. Lond. B Biol. 366, 9-16.
53. Kenyon, C., Chang, J., Gensch, E., Rud-ner, A., and Tabtiang, R. (1993). A C elegans mutant that lives twice as long as wild type. Nature 366, 461-464.
54. Kenyon, C. J. (2010b). The genetics of ageing. Nature 464, 504-512.
55. Kim, K., Sato, K., Shibuya, M., Zeiger, D M., Butcher, R. A., Ragains, J. R., Clardy, J., Touhara, K., and Sen-gupta, P. (2009). Two chemorecep-tors mediate developmental effects of dauer pheromone in C. elegans. Science 326, 994-998.
56. Kolesnick, R. (2002). The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J. Clin. Invest. 110,3-8.
57. Kundu, M., and Thompson, C. B. (2008). Autophagy: basic principles and relevance to disease. Annu. Rev. Pathol. 3, 427-455.
58. Lakowski, B., and Hekimi, S. (1996). Determination of life-span in Caenorhabditis elegans by four clock genes. Science 272, 1010-1013.
59. Lakowski, B., and Hekimi, S. (1998). The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 95, 13091-13096.
60. Lapierre, L. R., Gelino, S., Meléndez, A., and Hansen, M. (2011). Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans. Curr. Biol.21,1507-1514.
61. Lemire, B. D., Behrendt, M., DeCorby, A., and Gášková, D. (2009). C. elegans longevity pathways converge to decrease mitochondrial membrane potential. Mech. Ageing Dev. 130, 461-465.
62. Lucanic, M., Held, J. M., Vantipalli, M. C., Klang, I. M., Graham, J. B., Gibson, B. W., Lithgow, G. J., and Gill, M. S. (2011). N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans. Nature 473,226-229.
63. Maestro, M. A., Cardalda, C., Boj, S. F., Luco, R. F., Servitja, J. M., and Ferrer, J. (2007). Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. Endocr. Dev. 12, 33-45.
64. Marchi, S., Giorgi, C., Suski, J. M., Agnoletto, C., Bononi, A., Bonora, M., De Marchi, E., Missiroli, S., Patergnani, S., Poletti, F., Rimessi, A., Duszynski, J., Wieckowski, M. R., and Pinton, P. (2012). Mitochondria-ros crosstalk in the control of cell death and aging. J. Signal Transduct. 2012,1-17.
65. Matias, I., and Di Marzo, V. (2007). Endocannabinoids and the control of energy balance. Trends Endocrinol. Metab. 18,27-37.
66. McCormick, M., Chen, K., Ramaswamy, P., and Kenyon, C. (2012). New genes that extend Caenorhabditis elegans' lifespan in response to reproductive signals. Aging Cell 11, 192-202.
67. McGrath, P. T., Xu, Y., Ailion, M., Garrison, J. L., Butcher, R. A., and Bargmann, C. I. (2011). Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes. Nature 477,321-325.
68. McPartland, J. M., and Glass, M. (2003). Functional mapping of cannabinoid receptor homologs in mammals, other vertebrates, and invertebrates. Gene 312,297-303.
69. Meléndez, A., Tallóczy, Z., Seaman, M., Eskelinen, E.-L., Hall, D. H., and Levine, B. (2003). Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301,1387-1391.
70. Motola, D. L., Cummins, C. L., Rottiers, V., Sharma, K. K., Li, T., Li, Y., Suino-Powell, K., Xu, H. E., Auchus, R. J., Antebi, A., and Mangelsdorf, D. J. (2006). Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans. Cell 124, 1209-1223.
71. Mukhopadhyay, A., Deplancke, B., Wal-hout, A. J. M., and Tissenbaum, H. A. (2005). C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab. 2, 35-42.
72. Murphy, C. T., McCarroll, S. A., Bargmann, C. I., Fraser, A., Kamath, R. S., Ahringer, J., Li, H., and Kenyon, C. (2003). Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277-283.
73. Nicholls, D. G. (2002). Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease. Int. J. Biochem. Cell Biol. 34, 1372-1381.
74. O'Rourke, E. J., Soukas, A. A., Carr, C. E., and Ruvkun, G. (2009). C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell Metab. 10, 430-435.
75. Palanker, L., Tennessen, J. M., Lam, G., and Thummel, C. S. (2009). Drosophila HNF4 regulates lipid mobilization and beta-oxidation. Cell Metab. 9,228-239.
76. Pan, K. Z., Palter, J. E., Rogers, A. N., Olsen, A., Chen, D., Lithgow, G. J., and Kapahi, P. (2007). Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6, 111-119.
77. Park, D., Jones, K. L., Lee, H., Snutch, T. P., Taubert, S., and Riddle, D. L. (2012). Repression of a potassium channel by nuclear hormone receptor and TGF-β signaling modulates insulin signaling in Caenorhabditis elegans. PLoS Genet. 8, e1002519. doi:10.1371/journal.pgen.1002519
78. Perez, C. L., and Van Gilst, M. R. (2008). A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. CellMetab. 8,266-274.
79. Pungaliya, C., Srinivasan, J., Fox, B. W., Malik, R. U., Ludewig, A. H., Sternberg, P. W., and Schroeder, F. C. (2009). A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 106, 7708.
80. Robinson-Rechavi, M., Maina, C. V., Gissendanner, C. R., Laudet, V., and Sluder, A. (2005). Explosive lineage-specific expansion of the orphan nuclear receptor HNF4 in nema-todes. J. Mol. Evol. 60, 577-586.
81. Rogers, A. N., Chen, D., Mccoll, G., Czer-wieniec, G., Felkey, K., Gibson, B. W., Hubbard, A., Melov, S., Lithgow, G. J., and Kapahi, P. (2011). Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab. 14, 55-66.
82. Sakamoto, T., Inoue, T., Otomo, Y., Yokomori, N., Ohno, M., Arai, H., and Nakagawa, Y. (2012). Deficiency of cardiolipin synthase causes abnormal mitochondrial function and morphology in germ cells of Caenorhabditis elegans. J. Biol. Chem. 287, 4590-4601.
83. Shmookler Reis, R.J., Xu,L., Lee, H., Chae, M.,Thaden, J.J., Bharill, P., Tazearslan, C., Siegel, E., Alla, R., Zimniak, P., and Ayyadevara, S. (2011). Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants. Aging (Albany N.Y.) 3, 125.
84. Srinivasan, J., von Reuss, S. H., Bose, N., Zaslaver, A., Mahanti, P., Ho, M. C., O'Doherty, O. G., Edison, A. S., Sternberg, P. W., and Schroeder, F. C. (2012). A modular library of small molecule signals regulates social behaviors in Caenorhabditis elegans. PLoS Biol. 10, e1001237. doi:10.1371/journal.pbio.1001237
85. Srinivasan, S., Sadegh, L., Elle, I. C., Christensen, A. G. L., Faergeman, N. J., and Ashrafi, K. (2008). Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms. Cell Metab. 7, 533-544.
86. Subramaniam, S., Fahy, E., Gupta, S., Sud, M., Byrnes, R. W., Cotter, D., Dinasarapu, A. R., and Maurya, M. R. (2011). Bioinformatics and systems biology of the lipidome. Chem. Rev. 111,6452-6490.
87. Taubert, S., Hansen, M., Van Gilst, M. R., Cooper, S. B., and Yamamoto, K. R. (2008). The mediator sub-unit MDT-15 confers metabolic adaptation to ingested material. PLoS Genet. 4, e1000021. doi:10.1371/journal.pgen.1000021
88. Taubert, S., Van Gilst, M. R., Hansen, M., and Yamamoto, K. R. (2006). A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans. Genes Dev. 20, 1137-1149.
89. Taubert, S., Ward, J. D., and Yamamoto, K. R. (2011). Nuclear hormone receptors in nematodes: evolution and function. Mol. Cell. Endocrinol. 334, 49-55.
90. Tedesco, P., Jiang, J., Wang, J., Jazwin-ski, S. M., and Johnson, T. E. (2008). Genetic analysis of hyl-1, the C. elegans homolog of LAG1/LASS1. Age (Dordr.) 30,43-52.
91. Tóth, M. L., Sigmond, T., Borsos, E., Barna, J., Erdélyi, P., Takács-Vellai, K., Orosz, L., Kovács, A. L., Csikós, G., Sass, M., and Vellai, T. (2008). Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4, 330-338.
92. Van Gilst, M. R., Hadjivassiliou, H., and Yamamoto, K. R. (2005a). A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49. Proc. Natl. Acad. Sci. U.S.A. 102, 13496-13501.
93. Van Gilst, M. R., Hadjivassiliou, H., Jolly, A., and Yamamoto, K. R. (2005b). Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans. PLoS Biol. 3, e53. doi:10.1371/jour-nal.pbio.0030053
94. Verme, J. L. (2005). The nuclear receptor peroxisome proliferator-activated receptor- mediates the anti-inflammatory actions of palmi-toylethanolamide. Mol. Pharmacol. 67, 15-19.
95. von Reuss, S. H., Bose, N., Srinivasan, J., Yim, J. J., Judkins, J. C., Sternberg, P. W., and Schroeder, F. C. (2012). Comparative metabolomics reveals biogenesis of ascarosides, a modular library of small-molecule signals in C. elegans. J. Am. Chem. Soc. 134, 1817-1824.
96. Walker, A. K., Jacobs, R. L., Watts, J. L., Rottiers, V, Jiang, K., Finnegan, D M., Shioda, T., Hansen, M., Yang, E, Niebergall, L. J., Vance, D. E., Tzoneva, M., Hart, A. C., and Näär, A. M. (2011). A conserved SREBP-1/phosphatidylcholine feedback cir cuit regulates lipogenesis in metazoans. Cell 147, 840-852.
97. Wang, M. C., Min, W., Freudiger, C. W., Ruvkun, G., and Xie, X. S. (2011). RNAi screening for fat regulatory genes with SRS microscopy. Nat. Methods 8, 135-138.
98. Wang, M. C., O'Rourke, E. J., and Ruvkun, G. (2008). Fat metabolism links germline stem cells and longevity in C. elegans. Science 322, 957-960.
99. Wong, A., Boutis, P., and Hekimi, S. (1995). Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics 139, 1247-1259.
100. Yang, F., Vought, B. W., Satterlee, J. S., Walker, A. K., Jim Sun, Z.-Y., Watts, J. L., DeBeaumont, R., Saito, R. M., Hyberts, S. G., Yang, S., Macol, C., Iyer, L., Tjian, R., van den Heuvel, S., Hart, A. C., Wagner, G., and Naeaer, A.M. (2006). An ARC/mediator sub-unit required for SREBP control of cholesterol and lipid homeostasis. Nature 442, 700-704.
101. Yang, W., and Hekimi, S. (2010). A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 8, e1000556. doi:10.1371/journal.pbio.1000556
102. Youngman, M. J., Rogers, Z. N., and Kim, D. H. (2011). A decline in p38 MAPK signaling underlies immunosenescence in Caenorhabditis elegans. PLoS Genet. 7, e1002082. doi:10.1371/journal.pgen.1002082
103. Yuan, X., Ta, T. C., Lin, M., Evans, J. R., Dong, Y., Bolotin, E., Sherman, M. A., Forman, B. M., and Sladek, F. M. (2009). Identification of an endogenous ligand bound to a native orphan nuclear receptor. PLoS ONE 4, e5609. doi:10.1371/jour-nal.pone.0005609
104. Zhang, S. O., Box, A. C., Xu, N., Le Men, J., Yu, J., Guo, F., Trimble, R., and Mak, H. Y. (2010). Genetic and dietary regulation of lipid droplet expansion in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 107, 4640-4645.
105. Zhou, K. I., Pincus, Z., and Slack, F. J. (2011). Longevity and stress in Caenorhabditis elegans. Aging (Albany N.Y.) 3,733.