Sterol metabolites are critical signaling molecules that regulate metabolism, development, and homeostasis. Oxysterols, bile acids (BAs), and steroids work primarily through cognate sterol-responsive nuclear hormone receptors to control these processes through feed-forward and feedback mechanisms. These signaling pathways are conserved from simple invertebrates to mammals. Indeed, results from various model organisms have yielded fundamental insights into cholesterol and BA homeostasis, lipid and glucose metabolism, protective mechanisms, tissue differentiation, development, reproduction, and even aging. Here, we review how sterols act through evolutionarily ancient mechanisms to control these processes.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Simons K, Ikonen E. 1.  2000. How cells handle cholesterol. Science 290:1721–26 [Google Scholar]
  2. Gill S, Chow R, Brown AJ. 2.  2008. Sterol regulators of cholesterol homeostasis and beyond: the oxysterol hypothesis revisited and revised. Prog. Lipid Res. 47:391–404 [Google Scholar]
  3. Redinger RN.3.  2003. The coming of age of our understanding of the enterohepatic circulation of bile salts. Am. J. Surg. 185:168–72 [Google Scholar]
  4. Hu J, Zhang Z, Shen WJ, Azhar S. 4.  2010. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones. Nutr. Metab. 7:47 [Google Scholar]
  5. Dusso AS, Brown AJ, Slatopolsky E. 5.  2005. Vitamin D. Am. J. Physiol. Renal. Physiol. 289:F8–28 [Google Scholar]
  6. Magner DB, Antebi A. 6.  2008. Caenorhabditis elegans nuclear receptors: insights into life traits. Trends Endocrinol. Metab. 19:153–60 [Google Scholar]
  7. King-Jones K, Thummel CS. 7.  2005. Nuclear receptors—a perspective from Drosophila. Nat. Rev. Genet. 6:311–23 [Google Scholar]
  8. Horner MA, Pardee K, Liu S, King-Jones K, Lajoie G. 8.  et al. 2009. The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis. Genes Dev. 23:2711–16 [Google Scholar]
  9. Sieber MH, Thummel CS. 9.  2009. The DHR96 nuclear receptor controls triacylglycerol homeostasis in Drosophila. Cell Metab. 10:481–90 [Google Scholar]
  10. Fielenbach N, Antebi A. 10.  2008. C. elegans dauer formation and the molecular basis of plasticity. Genes Dev. 22:2149–65 [Google Scholar]
  11. Espenshade PJ, Hughes AL. 11.  2007. Regulation of sterol synthesis in eukaryotes. Annu. Rev. Genet. 41:401–27 [Google Scholar]
  12. Zhao C, Dahlman-Wright K. 12.  2010. Liver X receptor in cholesterol metabolism. J. Endocrinol. 204:233–40 [Google Scholar]
  13. Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA. 13.  et al. 1999. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc. Natl. Acad. Sci. USA 96:266–71 [Google Scholar]
  14. Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM. 14.  et al. 1998. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 93:693–704 [Google Scholar]
  15. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB. 15.  et al. 1997. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J. Biol. Chem. 272:3137–40 [Google Scholar]
  16. Barbier O, Trottier J, Kaeding J, Caron P, Verreault M. 16.  2009. Lipid-activated transcription factors control bile acid glucuronidation. Mol. Cell Biochem. 326:3–8 [Google Scholar]
  17. Kalaany NY, Mangelsdorf DJ. 17.  2006. LXRS and FXR: the yin and yang of cholesterol and fat metabolism. Annu. Rev. Physiol. 68:159–91 [Google Scholar]
  18. Zelcer N, Tontonoz P. 18.  2006. Liver X receptors as integrators of metabolic and inflammatory signaling. J. Clin. Investig. 116:607–14 [Google Scholar]
  19. Duval C, Touche V, Tailleux A, Fruchart JC, Fievet C. 19.  et al. 2006. Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine. Biochem. Biophys. Res. Commun. 340:1259–63 [Google Scholar]
  20. Luo Y, Liang CP, Tall AR. 20.  2001. The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. J. Biol. Chem. 276:24767–73 [Google Scholar]
  21. Levin N, Bischoff ED, Daige CL, Thomas D, Vu CT. 21.  et al. 2005. Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists. Arterioscler. Thromb. Vasc. Biol. 25:135–42 [Google Scholar]
  22. Rigamonti E, Helin L, Lestavel S, Mutka AL, Lepore M. 22.  et al. 2005. Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Circ. Res. 97:682–89 [Google Scholar]
  23. Dai XY, Ou X, Hao XR, Cao DL, Tang YL. 23.  et al. 2008. The effect of T0901317 on ATP-binding cassette transporter A1 and Niemann-Pick type C1 in apoE-/- mice. J. Cardiovasc. Pharmacol. 51:467–75 [Google Scholar]
  24. Repa JJ, Li H, Frank-Cannon TC, Valasek MA, Turley SD. 24.  et al. 2007. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J. Neurosci. 27:14470–80 [Google Scholar]
  25. Zhang JR, Coleman T, Langmade SJ, Scherrer DE, Lane L. 25.  et al. 2008. Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking. J. Clin. Investig. 118:2281–90 [Google Scholar]
  26. Cummins CL, Volle DH, Zhang Y, McDonald JG, Sion B. 26.  et al. 2006. Liver X receptors regulate adrenal cholesterol balance. J. Clin. Investig. 116:1902–12 [Google Scholar]
  27. Nilsson M, Stulnig TM, Lin CY, Yeo AL, Nowotny P. 27.  et al. 2007. Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary-adrenal feedback. Mol. Endocrinol. 21:126–37 [Google Scholar]
  28. Christenson LK, McAllister JM, Martin KO, Javitt NB, Osborne TF, Strauss JF 3rd. 28.  1998. Oxysterol regulation of steroidogenic acute regulatory protein gene expression. Structural specificity and transcriptional and posttranscriptional actions. J. Biol. Chem. 273:30729–35 [Google Scholar]
  29. Beltowski J, Semczuk A. 29.  2010. Liver X receptor (LXR) and the reproductive system—a potential novel target for therapeutic intervention. Pharmacol. Rep. 62:15–27 [Google Scholar]
  30. Drouineaud V, Sagot P, Garrido C, Logette E, Deckert V. 30.  et al. 2007. Inhibition of progesterone production in human luteinized granulosa cells treated with LXR agonists. Mol. Hum. Reprod. 13:373–79 [Google Scholar]
  31. Steffensen KR, Robertson K, Gustafsson JA, Andersen CY. 31.  2006. Reduced fertility and inability of oocytes to resume meiosis in mice deficient of the Lxr genes. Mol. Cell Endocrinol. 256:9–16 [Google Scholar]
  32. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. 32.  1996. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383:728–31 [Google Scholar]
  33. Frenoux JM, Vernet P, Volle DH, Britan A, Saez F. 33.  et al. 2004. Nuclear oxysterol receptors, LXRs, are involved in the maintenance of mouse caput epididymidis structure and functions. J. Mol. Endocrinol. 33:361–75 [Google Scholar]
  34. Robertson KM, Schuster GU, Steffensen KR, Hovatta O, Meaney S. 34.  et al. 2005. The liver X receptor-beta is essential for maintaining cholesterol homeostasis in the testis. Endocrinology 146:2519–30 [Google Scholar]
  35. Volle DH, Mouzat K, Duggavathi R, Siddeek B, Dechelotte P. 35.  et al. 2007. Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility. Mol. Endocrinol. 21:1014–27 [Google Scholar]
  36. Russell DW.36.  2003. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72:137–74 [Google Scholar]
  37. Wang YD, Chen WD, Moore DD, Huang W. 37.  2008. FXR: a metabolic regulator and cell protector. Cell Res. 18:1087–95 [Google Scholar]
  38. Kim I, Morimura K, Shah Y, Yang Q, Ward JM, Gonzalez FJ. 38.  2007. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 28:940–46 [Google Scholar]
  39. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ. 39.  2000. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102:731–44 [Google Scholar]
  40. Kok T, Hulzebos CV, Wolters H, Havinga R, Agellon LB. 40.  et al. 2003. Enterohepatic circulation of bile salts in farnesoid X receptor–deficient mice: efficient intestinal bile salt absorption in the absence of ileal bile acid-binding protein. J. Biol. Chem. 278:41930–37 [Google Scholar]
  41. Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. 41.  2009. Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev. 89:147–91 [Google Scholar]
  42. Choi M, Moschetta A, Bookout AL, Peng L, Umetani M. 42.  et al. 2006. Identification of a hormonal basis for gallbladder filling. Nat. Med. 12:1253–55 [Google Scholar]
  43. Zollner G, Marschall HU, Wagner M, Trauner M. 43.  2006. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations. Mol. Pharm. 3:231–51 [Google Scholar]
  44. Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J. 44.  2002. The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity. Mol. Endocrinol. 16:2065–76 [Google Scholar]
  45. Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA. 45.  et al. 2000. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol. Cell 6:507–15 [Google Scholar]
  46. Wang L, Lee YK, Bundman D, Han Y, Thevananther S. 46.  et al. 2002. Redundant pathways for negative feedback regulation of bile acid production. Dev. Cell 2:721–31 [Google Scholar]
  47. Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL. 47.  et al. 2005. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2:217–25 [Google Scholar]
  48. Holt JA, Luo G, Billin AN, Bisi J, McNeill YY. 48.  et al. 2003. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 17:1581–91 [Google Scholar]
  49. Ito S, Fujimori T, Furuya A, Satoh J, Nabeshima Y, Nabeshima YI. 49.  2005. Impaired negative feedback suppression of bile acid synthesis in mice lacking betaKlotho. J. Clin. Investig. 115:2202–8 [Google Scholar]
  50. Lambert G, Amar MJ, Guo G, Brewer HB Jr, Gonzalez FJ, Sinal CJ. 50.  2003. The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J. Biol. Chem. 278:2563–70 [Google Scholar]
  51. Watanabe M, Houten SM, Wang L, Moschetta A, Mangelsdorf DJ. 51.  et al. 2004. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J. Clin. Investig. 113:1408–18 [Google Scholar]
  52. Carnahan VE, Redinbo MR. 52.  2005. Structure and function of the human nuclear xenobiotic receptor PXR. Curr. Drug Metab. 6:357–67 [Google Scholar]
  53. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI. 53.  et al. 2001. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. USA 98:3369–74 [Google Scholar]
  54. Bachmann K, Patel H, Batayneh Z, Slama J, White D. 54.  et al. 2004. PXR and the regulation of apoA1 and HDL-cholesterol in rodents. Pharmacol. Res. 50:237–46 [Google Scholar]
  55. Sporstol M, Tapia G, Malerod L, Mousavi SA, Berg T. 55.  2005. Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptor class B type I. Biochem. Biophys. Res. Commun. 331:1533–41 [Google Scholar]
  56. Wada T, Gao J, Xie W. 56.  2009. PXR and CAR in energy metabolism. Trends Endocrinol. Metab. 20:273–79 [Google Scholar]
  57. Zhang J, Huang W, Qatanani M, Evans RM, Moore DD. 57.  2004. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J. Biol. Chem. 279:49517–22 [Google Scholar]
  58. Wei P, Zhang J, Egan-Hafley M, Liang S, Moore DD. 58.  2000. The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 407:920–23 [Google Scholar]
  59. Masson D, Qatanani M, Sberna AL, Xiao R, Pais de Barros JP. 59.  et al. 2008. Activation of the constitutive androstane receptor decreases HDL in wild-type and human apoA-I transgenic mice. J. Lipid. Res. 49:1682–91 [Google Scholar]
  60. Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H. 60.  et al. 2002. Vitamin D receptor as an intestinal bile acid sensor. Science 296:1313–16 [Google Scholar]
  61. Nagpal S, Na S, Rathnachalam R. 61.  2005. Noncalcemic actions of vitamin D receptor ligands. Endocr. Rev. 26:662–87 [Google Scholar]
  62. Wong KE, Szeto FL, Zhang W, Ye H, Kong J. 62.  et al. 2009. Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins. Am. J. Physiol. Endocrinol. Metab. 296:E820–28 [Google Scholar]
  63. Hylemon PB, Zhou H, Pandak WM, Ren S, Gil G, Dent P. 63.  2009. Bile acids as regulatory molecules. J. Lipid. Res. 50:1509–20 [Google Scholar]
  64. Kim KM, Yoon JH, Gwak GY, Kim W, Lee SH. 64.  et al. 2006. Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells. Biochem. Biophys. Res. Commun. 342:1108–13 [Google Scholar]
  65. Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K. 65.  2008. Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 7:678–93 [Google Scholar]
  66. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J. 66.  et al. 2009. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 10:167–77 [Google Scholar]
  67. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM. 67.  et al. 2000. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 14:2819–30 [Google Scholar]
  68. Kalaany NY, Gauthier KC, Zavacki AM, Mammen PP, Kitazume T. 68.  et al. 2005. LXRs regulate the balance between fat storage and oxidation. Cell Metab. 1:231–44 [Google Scholar]
  69. Cha JY, Repa JJ. 69.  2007. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J. Biol. Chem. 282:743–51 [Google Scholar]
  70. Tontonoz P, Mangelsdorf DJ. 70.  2003. Liver X receptor signaling pathways in cardiovascular disease. Mol. Endocrinol. 17:985–93 [Google Scholar]
  71. Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R. 71.  et al. 2008. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology 134:556–67 [Google Scholar]
  72. Kase ET, Wensaas AJ, Aas V, Hojlund K, Levin K. 72.  et al. 2005. Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway. Diabetes 54:1108–15 [Google Scholar]
  73. Stenson BM, Ryden M, Steffensen KR, Wahlen K, Pettersson AT. 73.  et al. 2009. Activation of liver X receptor regulates substrate oxidation in white adipocytes. Endocrinology 150:4104–13 [Google Scholar]
  74. Hu T, Foxworthy P, Siesky A, Ficorilli JV, Gao H. 74.  et al. 2005. Hepatic peroxisomal fatty acid beta-oxidation is regulated by liver X receptor alpha. Endocrinology 146:5380–87 [Google Scholar]
  75. Bell GD, Lewis B, Petrie A, Dowling RH. 75.  1973. Serum lipids in cholelithiasis: effect of chenodeoxycholic acid therapy. Br. Med. J. 3:520–23 [Google Scholar]
  76. Hirokane H, Nakahara M, Tachibana S, Shimizu M, Sato R. 76.  2004. Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. J. Biol. Chem. 279:45685–92 [Google Scholar]
  77. Savkur RS, Bramlett KS, Michael LF, Burris TP. 77.  2005. Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor. Biochem. Biophys. Res. Commun. 329:391–96 [Google Scholar]
  78. Zhou J, Zhai Y, Mu Y, Gong H, Uppal H. 78.  et al. 2006. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J. Biol. Chem. 281:15013–20 [Google Scholar]
  79. Nakamura K, Moore R, Negishi M, Sueyoshi T. 79.  2007. Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver. J. Biol. Chem. 282:9768–76 [Google Scholar]
  80. Ueda A, Hamadeh HK, Webb HK, Yamamoto Y, Sueyoshi T. 80.  et al. 2002. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol. Pharmacol. 61:1–6 [Google Scholar]
  81. Kassam A, Winrow CJ, Fernandez-Rachubinski F, Capone JP, Rachubinski RA. 81.  2000. The peroxisome proliferator response element of the gene encoding the peroxisomal beta-oxidation enzyme enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase is a target for constitutive androstane receptor beta/9-cis-retinoic acid receptor-mediated transactivation. J. Biol. Chem. 275:4345–50 [Google Scholar]
  82. Maglich JM, Lobe DC, Moore JT. 82.  2009. The nuclear receptor CAR (NR1I3) regulates serum triglyceride levels under conditions of metabolic stress. J. Lipid Res. 50:439–45 [Google Scholar]
  83. Dong B, Saha PK, Huang W, Chen W, Abu-Elheiga LA. 83.  et al. 2009. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc. Natl. Acad. Sci. USA 106:18831–36 [Google Scholar]
  84. Roth A, Looser R, Kaufmann M, Blattler SM, Rencurel F. 84.  et al. 2008. Regulatory cross-talk between drug metabolism and lipid homeostasis: constitutive androstane receptor and pregnane X receptor increase Insig-1 expression. Mol. Pharmacol. 73:1282–89 [Google Scholar]
  85. Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S. 85.  et al. 2003. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc. Natl. Acad. Sci. USA 100:5419–24 [Google Scholar]
  86. Stulnig TM, Steffensen KR, Gao H, Reimers M, Dahlman-Wright K. 86.  et al. 2002. Novel roles of liver X receptors exposed by gene expression profiling in liver and adipose tissue. Mol. Pharmacol. 62:1299–305 [Google Scholar]
  87. Gerin I, Dolinsky VW, Shackman JG, Kennedy RT, Chiang SH. 87.  et al. 2005. LXRbeta is required for adipocyte growth, glucose homeostasis, and beta cell function. J. Biol. Chem. 280:23024–31 [Google Scholar]
  88. Sugden MC, Holness MJ. 88.  2008. Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance. Biochem. Soc. Trans. 36:891–900 [Google Scholar]
  89. Mitro N, Mak PA, Vargas L, Godio C, Hampton E. 89.  et al. 2007. The nuclear receptor LXR is a glucose sensor. Nature 445:219–23 [Google Scholar]
  90. Oosterveer MH, van Dijk TH, Grefhorst A, Bloks VW, Havinga R. 90.  et al. 2008. Lxralpha deficiency hampers the hepatic adaptive response to fasting in mice. J. Biol. Chem. 283:25437–45 [Google Scholar]
  91. Stayrook KR, Bramlett KS, Savkur RS, Ficorilli J, Cook T. 91.  et al. 2005. Regulation of carbohydrate metabolism by the farnesoid X receptor. Endocrinology 146:984–91 [Google Scholar]
  92. Cariou B, van Harmelen K, Duran-Sandoval D, van Dijk TH, Grefhorst A. 92.  et al. 2006. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J. Biol. Chem. 281:11039–49 [Google Scholar]
  93. Zhang Y, Lee FY, Barrera G, Lee H, Vales C. 93.  et al. 2006. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc. Natl. Acad. Sci. USA 103:1006–11 [Google Scholar]
  94. Ma K, Saha PK, Chan L, Moore DD. 94.  2006. Farnesoid X receptor is essential for normal glucose homeostasis. J. Clin. Investig. 116:1102–9 [Google Scholar]
  95. Rizzo G, Disante M, Mencarelli A, Renga B, Gioiello A. 95.  et al. 2006. The farnesoid X receptor promotes adipocyte differentiation and regulates adipose cell function in vivo. Mol. Pharmacol. 70:1164–73 [Google Scholar]
  96. Renga B, Mencarelli A, Vavassori P, Brancaleone V, Fiorucci S. 96.  2010. The bile acid sensor FXR regulates insulin transcription and secretion. Biochim. Biophys. Acta 1802:363–72 [Google Scholar]
  97. Cariou B, van Harmelen K, Duran-Sandoval D, van Dijk T, Grefhorst A. 97.  et al. 2005. Transient impairment of the adaptive response to fasting in FXR-deficient mice. FEBS Lett. 579:4076–80 [Google Scholar]
  98. Cariou B, Bouchaert E, Abdelkarim M, Dumont J, Caron S. 98.  et al. 2007. FXR-deficiency confers increased susceptibility to torpor. FEBS Lett. 581:5191–98 [Google Scholar]
  99. Venkatesan N, Davidson MB, Simsolo RB, Kern PA. 99.  1994. Phenobarbital treatment enhances insulin-mediated glucose metabolism and improves lipid metabolism in the diabetic rat. Metabolism 43:348–56 [Google Scholar]
  100. Maglich JM, Watson J, McMillen PJ, Goodwin B, Willson TM, Moore JT. 100.  2004. The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. J. Biol. Chem. 279:19832–38 [Google Scholar]
  101. Ding X, Lichti K, Kim I, Gonzalez FJ, Staudinger JL. 101.  2006. Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor alpha, and the coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha. J. Biol. Chem. 281:26540–51 [Google Scholar]
  102. Palomer X, Gonzalez-Clemente JM, Blanco-Vaca F, Mauricio D. 102.  2008. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes. Metab. 10:185–97 [Google Scholar]
  103. Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P. 103.  2003. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat. Med. 9:213–19 [Google Scholar]
  104. Ogawa S, Lozach J, Benner C, Pascual G, Tangirala RK. 104.  et al. 2005. Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122:707–21 [Google Scholar]
  105. Patel R, Patel M, Tsai R, Lin V, Bookout AL. 105.  et al. 2011. LXRbeta is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice. J. Clin. Investig. 121:431–41 [Google Scholar]
  106. Ghisletti S, Huang W, Ogawa S, Pascual G, Lin ME. 106.  et al. 2007. Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol. Cell 25:57–70 [Google Scholar]
  107. Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC. 107.  et al. 2005. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437:759–63 [Google Scholar]
  108. Wang YD, Chen WD, Wang M, Yu D, Forman BM, Huang W. 108.  2008. Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response. Hepatology 48:1632–43 [Google Scholar]
  109. Moreau A, Vilarem MJ, Maurel P, Pascussi JM. 109.  2008. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol. Pharm. 5:35–41 [Google Scholar]
  110. Hu G, Xu C, Staudinger JL. 110.  2010. Pregnane x receptor is SUMOylated to repress the inflammatory response. J. Pharmacol. Exp. Ther. 335:342–50 [Google Scholar]
  111. Vavassori P, Mencarelli A, Renga B, Distrutti E, Fiorucci S. 111.  2009. The bile acid receptor FXR is a modulator of intestinal innate immunity. J. Immunol. 183:6251–61 [Google Scholar]
  112. Zimmerman TL, Thevananther S, Ghose R, Burns AR, Karpen SJ. 112.  2006. Nuclear export of retinoid X receptor alpha in response to interleukin-1beta-mediated cell signaling: roles for JNK and SER260. J. Biol. Chem. 281:15434–40 [Google Scholar]
  113. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA. 113.  et al. 2004. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119:299–309 [Google Scholar]
  114. Rahman I, Biswas SK, Kirkham PA. 114.  2006. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem. Pharmacol. 72:1439–52 [Google Scholar]
  115. Bensinger SJ, Bradley MN, Joseph SB, Zelcer N, Janssen EM. 115.  et al. 2008. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134:97–111 [Google Scholar]
  116. Martínez-Botas J, Ferruelo AJ, Suárez Y, Fernández C, Gómez-Coronado D, Lasunción MA. 116.  2001. Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives. Biochim. Biophys. Acta1532185–94 [Google Scholar]
  117. Dubrac S, Elentner A, Ebner S, Horejs-Hoeck J, Schmuth M. 117.  2010. Modulation of T lymphocyte function by the pregnane X receptor. J. Immunol. 184:2949–57 [Google Scholar]
  118. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. 118.  2010. Vitamin D: modulator of the immune system. Curr. Opin. Pharmacol. 10:482–96 [Google Scholar]
  119. Schmuth M, Jiang YJ, Dubrac S, Elias PM, Feingold KR. 119.  2008. Thematic review series: skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology. J. Lipid Res. 49:499–509 [Google Scholar]
  120. Chang KC, Shen Q, Oh IG, Jelinsky SA, Jenkins SF. 120.  et al. 2008. Liver X receptor is a therapeutic target for photoaging and chronological skin aging. Mol. Endocrinol. 22:2407–19 [Google Scholar]
  121. Sacchetti P, Sousa KM, Hall AC, Liste I, Steffensen KR. 121.  et al. 2009. Liver X receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells. Cell Stem Cell 5:409–19 [Google Scholar]
  122. Wang L, Schuster GU, Hultenby K, Zhang Q, Andersson S, Gustafsson JA. 122.  2002. Liver X receptors in the central nervous system: from lipid homeostasis to neuronal degeneration. Proc. Natl. Acad. Sci. USA 99:13878–83 [Google Scholar]
  123. Andersson S, Gustafsson N, Warner M, Gustafsson JA. 123.  2005. Inactivation of liver X receptor beta leads to adult-onset motor neuron degeneration in male mice. Proc. Natl. Acad. Sci. USA 102:3857–62 [Google Scholar]
  124. Kha HT, Basseri B, Shouhed D, Richardson J, Tetradis S. 124.  et al. 2004. Oxysterols regulate differentiation of mesenchymal stem cells: pro-bone and anti-fat. J. Bone Miner. Res. 19:830–40 [Google Scholar]
  125. Richardson JA, Amantea CM, Kianmahd B, Tetradis S, Lieberman JR. 125.  et al. 2007. Oxysterol-induced osteoblastic differentiation of pluripotent mesenchymal cells is mediated through a PKC- and PKA-dependent pathway. J. Cell Biochem. 100:1131–45 [Google Scholar]
  126. Dwyer JR, Sever N, Carlson M, Nelson SF, Beachy PA, Parhami F. 126.  2007. Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells. J. Biol. Chem. 282:8959–68 [Google Scholar]
  127. Corcoran RB, Scott MP. 127.  2006. Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc. Natl. Acad. Sci. USA 103:8408–13 [Google Scholar]
  128. Kim WK, Meliton V, Park KW, Hong C, Tontonoz P. 128.  et al. 2009. Negative regulation of hedgehog signaling by liver X receptors. Mol. Endocrinol. 23:1532–43 [Google Scholar]
  129. Fausto N, Campbell JS, Riehle KJ. 129.  2006. Liver regeneration. Hepatology 43:S45–53 [Google Scholar]
  130. Huang W, Ma K, Zhang J, Qatanani M, Cuvillier J. 130.  et al. 2006. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 312:233–36 [Google Scholar]
  131. Chen WD, Wang YD, Zhang L, Shiah S, Wang M. 131.  et al. 2010. Farnesoid X receptor alleviates age-related proliferation defects in regenerating mouse livers by activating forkhead box m1b transcription. Hepatology 51:953–62 [Google Scholar]
  132. Wang X, Krupczak-Hollis K, Tan Y, Dennewitz MB, Adami GR, Costa RH. 132.  2002. Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kip1 protein levels and increased Cdc25B expression. J. Biol. Chem. 277:44310–16 [Google Scholar]
  133. Guo GL, Lambert G, Negishi M, Ward JM, Brewer HB Jr. 133.  et al. 2003. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J. Biol. Chem. 278:45062–71 [Google Scholar]
  134. Yamamoto Y, Moore R, Goldsworthy TL, Negishi M, Maronpot RR. 134.  2004. The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. Cancer Res. 64:7197–200 [Google Scholar]
  135. Huang W, Zhang J, Washington M, Liu J, Parant JM. 135.  et al. 2005. Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor. Mol. Endocrinol. 19:1646–53 [Google Scholar]
  136. Staudinger J, Liu Y, Madan A, Habeebu S, Klaassen CD. 136.  2001. Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor. Drug Metab. Dispos. 29:1467–72 [Google Scholar]
  137. Dai G, He L, Bu P, Wan YJ. 137.  2008. Pregnane X receptor is essential for normal progression of liver regeneration. Hepatology 47:1277–87 [Google Scholar]
  138. Ethier C, Kestekian R, Beaulieu C, Dube C, Havrankova J, Gascon-Barre M. 138.  1990. Vitamin D depletion retards the normal regeneration process after partial hepatectomy in the rat. Endocrinology 126:2947–59 [Google Scholar]
  139. Koldamova R, Lefterov I. 139.  2007. Role of LXR and ABCA1 in the pathogenesis of Alzheimer's disease—implications for a new therapeutic approach. Curr. Alzheimer Res. 4:171–78 [Google Scholar]
  140. Fitz NF, Cronican A, Pham T, Fogg A, Fauq AH. 140.  et al. 2010. Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice. J. Neurosci. 30:6862–72 [Google Scholar]
  141. Adighibe O, Arepalli S, Duckworth J, Hardy J, Wavrant-De Vrièze F. 141.  2006. Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease. Neurobiol. Aging 27:1431–34 [Google Scholar]
  142. Mooijaart SP, Kuningas M, Westendorp RG, Houwing-Duistermaat JJ, Slagboom PE. 142.  et al. 2007. Liver X receptor alpha associates with human life span. J. Gerontol. A 62:343–49 [Google Scholar]
  143. Keisala T, Minasyan A, Lou YR, Zou J, Kalueff AV. 143.  et al. 2009. Premature aging in vitamin D receptor mutant mice. J. Steroid Biochem. Mol. Biol. 115:91–97 [Google Scholar]
  144. Dardenne O, Prud'homme J, Arabian A, Glorieux FH, St-Arnaud R. 144.  2001. Targeted inactivation of the 25-hydroxyvitamin D3-1alpha-hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D-deficiency rickets. Endocrinology 142:3135–41 [Google Scholar]
  145. Lanske B, Razzaque MS. 145.  2007. Premature aging in klotho mutant mice: Cause or consequence?. Ageing Res. Rev. 6:73–79 [Google Scholar]
  146. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A. 146.  et al. 2005. Suppression of aging in mice by the hormone Klotho. Science 309:1829–33 [Google Scholar]
  147. McElwee JJ, Schuster E, Blanc E, Thomas JH, Gems D. 147.  2004. Shared transcriptional signature in Caenorhabditis elegans dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J. Biol. Chem. 279:44533–43 [Google Scholar]
  148. Tsuchiya T, Dhahbi JM, Cui X, Mote PL, Bartke A, Spindler SR. 148.  2004. Additive regulation of hepatic gene expression by dwarfism and caloric restriction. Physiol. Genomics 17:307–15 [Google Scholar]
  149. Amador-Noguez D, Yagi K, Venable S, Darlington G. 149.  2004. Gene expression profile of long-lived Ames dwarf mice and Little mice. Aging Cell 3:423–41 [Google Scholar]
  150. Amador-Noguez D, Dean A, Huang W, Setchell K, Moore D, Darlington G. 150.  2007. Alterations in xenobiotic metabolism in the long-lived Little mice. Aging Cell 6:453–70 [Google Scholar]
  151. Gerisch B, Rottiers V, Li D, Motola DL, Cummins CL. 151.  et al. 2007. A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling. Proc. Natl. Acad. Sci. USA 104:5014–19 [Google Scholar]
  152. Fisher AL, Lithgow GJ. 152.  2006. The nuclear hormone receptor DAF-12 has opposing effects on Caenorhabditis elegans lifespan and regulates genes repressed in multiple long-lived worms. Aging Cell 5:127–38 [Google Scholar]
  153. Entchev EV, Kurzchalia TV. 153.  2005. Requirement of sterols in the life cycle of the nematode Caenorhabditis elegans. Semin. Cell Dev. Biol. 16:175–82 [Google Scholar]
  154. Cooke J, Sang JH. 154.  1970. Utilization of sterols by larvae of Drosophila melanogaster. J. Insect Physiol. 16:801–12 [Google Scholar]
  155. Chitwood DJ.155.  1999. Biochemistry and function of nematode steroids. Crit. Rev. Biochem. Mol. Biol. 34:273–84 [Google Scholar]
  156. Rewitz KF, Rybczynski R, Warren JT, Gilbert LI. 156.  2006. The Halloween genes code for cytochrome P450 enzymes mediating synthesis of the insect moulting hormone. Biochem. Soc. Trans. 34:1256–60 [Google Scholar]
  157. Baker KD, Shewchuk LM, Kozlova T, Makishima M, Hassell A. 157.  et al. 2003. The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway. Cell 113:731–42 [Google Scholar]
  158. Huang X, Warren JT, Gilbert LI. 158.  2008. New players in the regulation of ecdysone biosynthesis. J. Genet. Genomics 35:1–10 [Google Scholar]
  159. Wiese M, Antebi A, Zheng H. 159.  2010. Intracellular trafficking and synaptic function of APL-1 in Caenorhabditis elegans. PLoS ONE 5:e12790 [Google Scholar]
  160. Yochem J, Tuck S, Greenwald I, Han M. 160.  1999. A gp330/megalin-related protein is required in the major epidermis of Caenorhabditis elegans for completion of molting. Development 126:597–606 [Google Scholar]
  161. Li J, Brown G, Ailion M, Lee S, Thomas JH. 161.  2004. NCR-1 and NCR-2, the C. elegans homologs of the human Niemann-Pick type C1 disease protein, function upstream of DAF-9 in the dauer formation pathways. Development 131:5741–52 [Google Scholar]
  162. Kostrouchova M, Krause M, Kostrouch Z, Rall JE. 162.  2001. Nuclear hormone receptor CHR3 is a critical regulator of all four larval molts of the nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 98:7360–65 [Google Scholar]
  163. Gissendanner CR, Sluder AE. 163.  2000. nhr-25, the Caenorhabditis elegans ortholog of ftz-f1, is required for epidermal and somatic gonad development. Dev. Biol. 221:259–72 [Google Scholar]
  164. Tatar M, Yin C. 164.  2001. Slow aging during insect reproductive diapause: why butterflies, grasshoppers and flies are like worms. Exp. Gerontol. 36:723–38 [Google Scholar]
  165. Flatt T, Tu MP, Tatar M. 165.  2005. Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. BioEssays 27:999–1010 [Google Scholar]
  166. Simon AF, Shih C, Mack A, Benzer S. 166.  2003. Steroid control of longevity in Drosophila melanogaster. Science 299:1407–10 [Google Scholar]
  167. Maki A, Sawatsubashi S, Ito S, Shirode Y, Suzuki E. 167.  et al. 2004. Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers. Biochem. Biophys. Res. Commun. 320:262–67 [Google Scholar]
  168. Angelo G, Van Gilst MR. 168.  2009. Starvation protects germline stem cells and extends reproductive longevity in C. elegans. Science 326:954–58 [Google Scholar]
  169. Van Gilst MR, Hadjivassiliou H, Yamamoto KR. 169.  2005. A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49. Proc. Natl. Acad. Sci. USA 102:13496–501 [Google Scholar]
  170. Gerisch B, Weitzel C, Kober-Eisermann C, Rottiers V, Antebi A. 170.  2001. A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev. Cell 1:841–51 [Google Scholar]
  171. Yabe T, Suzuki N, Furukawa T, Ishihara T, Katsura I. 171.  2005. Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its export activity in Caenorhabditis elegans. Development 132:3197–207 [Google Scholar]
  172. Riddle DL, Swanson MM, Albert PS. 172.  1981. Interacting genes in nematode dauer larva formation. Nature 290:668–71 [Google Scholar]
  173. Antebi A, Yeh WH, Tait D, Hedgecock EM, Riddle DL. 173.  2000. daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes Dev. 14:1512–27 [Google Scholar]
  174. Vowels JJ, Thomas JH. 174.  1992. Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans. Genetics 130:105–23 [Google Scholar]
  175. Thomas JH, Birnby DA, Vowels JJ. 175.  1993. Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. Genetics 134:1105–17 [Google Scholar]
  176. Jia K, Albert PS, Riddle DL. 176.  2002. DAF-9, a cytochrome P450 regulating C. elegans larval development and adult longevity. Development 129:221–31 [Google Scholar]
  177. Motola DL, Cummins CL, Rottiers V, Sharma KK, Li T. 177.  et al. 2006. Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans. Cell 124:1209–23 [Google Scholar]
  178. Held JM, White MP, Fisher AL, Gibson BW, Lithgow GJ, Gill MS. 178.  2006. DAF-12-dependent rescue of dauer formation in Caenorhabditis elegans by (25S)-cholestenoic acid. Aging Cell 5:283–91 [Google Scholar]
  179. Song C, Liao S. 179.  2000. Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha. Endocrinology 141:4180–84 [Google Scholar]
  180. Ludewig AH, Kober-Eisermann C, Weitzel C, Bethke A, Neubert K. 180.  et al. 2004. A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging. Genes Dev. 18:2120–33 [Google Scholar]
  181. Rottiers V, Motola DL, Gerisch B, Cummins CL, Nishiwaki K. 181.  et al. 2006. Hormonal control of C. elegans dauer formation and life span by a Rieske-like oxygenase. Dev. Cell 10:473–82 [Google Scholar]
  182. Yoshiyama T, Namiki T, Mita K, Kataoka H, Niwa R. 182.  2006. Neverland is an evolutionally conserved Rieske-domain protein that is essential for ecdysone synthesis and insect growth. Development 133:2565–74 [Google Scholar]
  183. Dumas KJ, Guo C, Wang X, Burkhart KB, Adams EJ. 183.  et al. 2010. Functional divergence of dafachronic acid pathways in the control of C. elegans development and lifespan. Dev. Biol. 340:605–12 [Google Scholar]
  184. Gerisch B, Antebi A. 184.  2004. Hormonal signals produced by DAF-9/cytochrome P450 regulate C. elegans dauer diapause in response to environmental cues. Development 131:1765–76 [Google Scholar]
  185. Mak HY, Ruvkun G. 185.  2004. Intercellular signaling of reproductive development by the C. elegans DAF-9 cytochrome P450. Development 131:1777–86 [Google Scholar]
  186. Wang Z, Zhou XE, Motola DL, Gao X, Suino-Powell K. 186.  et al. 2009. Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes. Proc. Natl. Acad. Sci. USA 106:9138–43 [Google Scholar]
  187. Ogawa A, Streit A, Antebi A, Sommer RJ. 187.  2009. A conserved endocrine mechanism controls the formation of dauer and infective larvae in nematodes. Curr. Biol. 19:67–71 [Google Scholar]
  188. Bento G, Ogawa A, Sommer RJ. 188.  2010. Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution. Nature 466:494–97 [Google Scholar]
  189. Hannich JT, Entchev EV, Mende F, Boytchev H, Martin R. 189.  et al. 2009. Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans. Dev. Cell 16:833–43 [Google Scholar]
  190. Antebi A, Culotti JG, Hedgecock EM. 190.  1998. daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans. Development 125:1191–205 [Google Scholar]
  191. Bethke A, Fielenbach N, Wang Z, Mangelsdorf DJ, Antebi A. 191.  2009. Nuclear hormone receptor regulation of microRNAs controls developmental progression. Science 324:95–98 [Google Scholar]
  192. Abbott AL, Alvarez-Saavedra E, Miska EA, Lau NC, Bartel DP. 192.  et al. 2005. The let-7 microRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev. Cell 9:403–14 [Google Scholar]
  193. Mallanna SK, Rizzino A. 193.  2010. Emerging roles of microRNAs in the control of embryonic stem cells and the generation of induced pluripotent stem cells. Dev. Biol. 344:16–25 [Google Scholar]
  194. Caygill EE, Johnston LA. 194.  2008. Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAs. Curr. Biol. 18:943–50 [Google Scholar]
  195. Klass MR.195.  1977. Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech. Ageing Dev. 6:413–29 [Google Scholar]
  196. Lee SJ, Kenyon C. 196.  2009. Regulation of the longevity response to temperature by thermosensory neurons in Caenorhabditis elegans. Curr. Biol. 19:715–22 [Google Scholar]
  197. Hsin H, Kenyon C. 197.  1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362–66 [Google Scholar]
  198. Yamawaki TM, Berman JR, Suchanek-Kavipurapu M, McCormick M, Maria Gaglia M. 198.  et al. 2010. The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling. PLoS Biol. 8:e1000468 [Google Scholar]
  199. Berman JR, Kenyon C. 199.  2006. Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 124:1055–68 [Google Scholar]
  200. Wang MC, O'Rourke EJ, Ruvkun G. 200.  2008. Fat metabolism links germline stem cells and longevity in C. elegans. Science 322:957–60 [Google Scholar]
  201. Flatt T, Min KJ, D'Alterio C, Villa-Cuesta E, Cumbers J. 201.  et al. 2008. Drosophila germ-line modulation of insulin signaling and lifespan. Proc. Natl. Acad. Sci. USA 105:6368–73 [Google Scholar]
  202. Cargill SL, Carey JR, Muller HG, Anderson G. 202.  2003. Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell 2:185–90 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error