Molecules and Cells

  • 제45권11호
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  • Pages.763-770
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Recent Progress in Regulation of Aging by Insulin/IGF-1 Signaling in Caenorhabditis elegans

  • Lee, Hanseul (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Lee, Seung-Jae V. (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
  • 투고 : 2022.06.15
  • 심사 : 2022.08.20
  • 발행 : 2022.11.30
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초록

Caenorhabditis elegans has been used as a major model organism to identify genetic factors that regulate organismal aging and longevity. Insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) regulates aging in many species, ranging from nematodes to humans. C. elegans is a nonpathogenic genetic nematode model, which has been extensively utilized to identify molecular and cellular components that function in organismal aging and longevity. Here, we review the recent progress in the role of IIS in aging and longevity, which involves direct regulation of protein and RNA homeostasis, stress resistance, metabolism and the activities of the endocrine system. We also discuss recently identified genetic factors that interact with canonical IIS components to regulate aging and health span in C. elegans. We expect this review to provide valuable insights into understanding animal aging, which could eventually help develop anti-aging drugs for humans.

키워드

과제정보

We thank all Lee laboratory members for helpful comments and discussion. This research was supported by the KAIST Key Research Institutes Project (Interdisciplinary Research Group) to S.J.V.L.

참고문헌

  1. Admasu, T.D., Chaithanya Batchu, K., Barardo, D., Ng, L.F., Lam, V.Y.M., Xiao, L., Cazenave-Gassiot, A., Wenk, M.R., Tolwinski, N.S., and Gruber, J. (2018). Drug synergy slows aging and improves healthspan through IGF and SREBP lipid signaling. Dev. Cell 47, 67-79.e5. https://doi.org/10.1016/j.devcel.2018.09.001
  2. Altintas, O., Park, S., and Lee, S.J. (2016). The role of insulin/IGF-1 signaling in the longevity of model invertebrates, C. elegans and D. melanogaster. BMB Rep. 49, 81-92. https://doi.org/10.5483/BMBRep.2016.49.2.261
  3. Amrit, F.R.G., Naim, N., Ratnappan, R., Loose, J., Mason, C., Steenberge, L., McClendon, B.T., Wang, G., Driscoll, M., Yanowitz, J.L., et al. (2019). The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity. Nat. Commun. 10, 3042. https://doi.org/10.1038/s41467-019-10759-z
  4. An, S.W.A., Artan, M., Park, S., Altintas, O., and Lee, S.J.V. (2017). Longevity regulation by insulin/IGF-1 signalling. In Ageing: Lessons from C. elegans, A. Olsen and M. Gill, eds. (Cham, Switzerland: Springer), pp. 63-81.
  5. An, S.W.A., Choi, E.S., Hwang, W., Son, H.G., Yang, J.S., Seo, K., Nam, H.J., Nguyen, N.T.H., Kim, E.J.E., Suh, B.K., et al. (2019). KIN-4/MAST kinase promotes PTEN-mediated longevity of Caenorhabditis elegans via binding through a PDZ domain. Aging Cell 18, e12906. https://doi.org/10.1111/acel.12906
  6. Artan, M., Jeong, D.E., Lee, D., Kim, Y.I., Son, H.G., Husain, Z., Kim, J., Altintas, O., Kim, K., Alcedo, J., et al. (2016). Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides. Genes Dev. 30, 1047-1057. https://doi.org/10.1101/gad.279448.116
  7. Artan, M., Sohn, J., Lee, C., Park, S.Y., and Lee, S.V. (2022). MON-2, a Golgi protein, promotes longevity by upregulating autophagy through mediating inter-organelle communications. Autophagy 18, 1208-1210. https://doi.org/10.1080/15548627.2022.2039523
  8. Chang, J.T., Kumsta, C., Hellman, A.B., Adams, L.M., and Hansen, M. (2017). Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging. Elife 6, e18459. https://doi.org/10.7554/eLife.18459
  9. Depuydt, G., Shanmugam, N., Rasulova, M., Dhondt, I., and Braeckman, B.P. (2016). Increased protein stability and decreased protein turnover in the Caenorhabditis elegans Ins/IGF-1 daf-2 mutant. J. Gerontol. A Biol. Sci. Med. Sci. 71, 1553-1559. https://doi.org/10.1093/gerona/glv221
  10. Dhondt, I., Petyuk, V.A., Cai, H., Vandemeulebroucke, L., Vierstraete, A., Smith, R.D., Depuydt, G., and Braeckman, B.P. (2016). FOXO/DAF-16 activation slows down turnover of the majority of proteins in C. elegans. Cell Rep. 16, 3028-3040. https://doi.org/10.1016/j.celrep.2016.07.088
  11. Donato, V., Ayala, F.R., Cogliati, S., Bauman, C., Costa, J.G., Lenini, C., and Grau, R. (2017). Bacillus subtilis biofilm extends Caenorhabditis elegans longevity through downregulation of the insulin-like signalling pathway. Nat. Commun. 8, 14332. https://doi.org/10.1038/ncomms14332
  12. Dues, D.J., Schaar, C.E., Johnson, B.K., Bowman, M.J., Winn, M.E., Senchuk, M.M., and Van Raamsdonk, J.M. (2017). Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans. Free Radic. Biol. Med. 108, 362-373. https://doi.org/10.1016/j.freeradbiomed.2017.04.004
  13. Dzakah, E.E., Waqas, A., Wei, S., Yu, B., Wang, X., Fu, T., Liu, L., and Shan, G. (2018). Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans. J. Genet. Genomics 45, 651-662. https://doi.org/10.1016/j.jgg.2018.11.003
  14. Gao, A.W., Smith, R.L., van Weeghel, M., Kamble, R., Janssens, G.E., and Houtkooper, R.H. (2018). Identification of key pathways and metabolic fingerprints of longevity in C. elegans. Exp. Gerontol. 113, 128-140. https://doi.org/10.1016/j.exger.2018.10.003
  15. Grigolon, G., Araldi, E., Erni, R., Wu, J.Y., Thomas, C., La Fortezza, M., Laube, B., Pohlmann, D., Stoffel, M., Zarse, K., et al. (2022). Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan. Nat. Commun. 13, 107. https://doi.org/10.1038/s41467-021-27732-4
  16. Guevara-Aguirre, J., Balasubramanian, P., Guevara-Aguirre, M., Wei, M., Madia, F., Cheng, C.W., Hwang, D., Martin-Montalvo, A., Saavedra, J., Ingles, S., et al. (2011). Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci. Transl. Med. 3, 70ra13.
  17. Gusarov, I., Pani, B., Gautier, L., Smolentseva, O., Eremina, S., Shamovsky, I., Katkova-Zhukotskaya, O., Mironov, A., and Nudler, E. (2017). Glycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress. Nat. Commun. 8, 15868. https://doi.org/10.1038/ncomms15868
  18. Hwang, A.B., Jeong, D.E., and Lee, S.J. (2012). Mitochondria and organismal longevity. Curr. Genomics 13, 519-532. https://doi.org/10.2174/138920212803251427
  19. Hwang, A.B. and Lee, S.J. (2011). Regulation of life span by mitochondrial respiration: the HIF-1 and ROS connection. Aging (Albany N.Y.) 3, 304-310.
  20. Hwang, A.B., Ryu, E.A., Artan, M., Chang, H.W., Kabir, M.H., Nam, H.J., Lee, D., Yang, J.S., Kim, S., Mair, W.B., et al. (2014). Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A. 111, E4458-E4467.
  21. Jeong, D.E., Artan, M., Seo, K., and Lee, S.J. (2012). Regulation of lifespan by chemosensory and thermosensory systems: findings in invertebrates and their implications in mammalian aging. Front. Genet. 3, 218.
  22. Jung, Y., Kwon, S., Ham, S., Lee, D., Park, H.H., Yamaoka, Y., Jeong, D.E., Artan, M., Altintas, O., Park, S., et al. (2020). Caenorhabditis elegans Lipin 1 moderates the lifespan-shortening effects of dietary glucose by maintaining omega-6 polyunsaturated fatty acids. Aging Cell 19, e13150. https://doi.org/10.1111/acel.13150
  23. Kaletsky, R., Lakhina, V., Arey, R., Williams, A., Landis, J., Ashraf, J., and Murphy, C.T. (2016). The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators. Nature 529, 92-96. https://doi.org/10.1038/nature16483
  24. Kenyon, C., Chang, J., Gensch, E., Rudner, A., and Tabtiang, R. (1993). A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464. https://doi.org/10.1038/366461a0
  25. Kenyon, C.J. (2010). The genetics of ageing. Nature 464, 504-512. https://doi.org/10.1038/nature08980
  26. Kim, B., Lee, J., Kim, Y., and Lee, S.V. (2020a). Regulatory systems that mediate the effects of temperature on the lifespan of Caenorhabditis elegans. J. Neurogenet. 34, 518-526. https://doi.org/10.1080/01677063.2020.1781849
  27. Kim, E.J.E., Son, H.G., Park, H.H., Jung, Y., Kwon, S., and Lee, S.V. (2020b). Caenorhabditis elegans algn-2 is critical for longevity conferred by enhanced nonsense-mediated mRNA decay. iScience 23, 101713. https://doi.org/10.1016/j.isci.2020.101713
  28. Kim, S. and Kim, C. (2021). Transcriptomic analysis of cellular senescence: one step closer to senescence atlas. Mol. Cells 44, 136-145. https://doi.org/10.14348/molcells.2021.2239
  29. Kim, S.S. and Lee, S.V. (2019). Non-coding RNAs in Caenorhabditis elegans aging. Mol. Cells 42, 379-385.
  30. Kim, Y.K. and Maquat, L.E. (2019). UPFront and center in RNA decay: UPF1 in nonsense-mediated mRNA decay and beyond. RNA 25, 407-422. https://doi.org/10.1261/rna.070136.118
  31. Kimura, K.D., Tissenbaum, H.A., Liu, Y., and Ruvkun, G. (1997). daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942-946. https://doi.org/10.1126/science.277.5328.942
  32. Kinser, H.E. and Pincus, Z. (2020). MicroRNAs as modulators of longevity and the aging process. Hum. Genet. 139, 291-308. https://doi.org/10.1007/s00439-019-02046-0
  33. Kirkwood, T.B. (1977). Evolution of ageing. Nature 270, 301-304. https://doi.org/10.1038/270301a0
  34. Lai, C.H., Chou, C.Y., Ch'ang, L.Y., Liu, C.S., and Lin, W. (2000). Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome Res. 10, 703-713. https://doi.org/10.1101/gr.10.5.703
  35. Lee, D., Hwang, W., Artan, M., Jeong, D.E., and Lee, S.J. (2015a). Effects of nutritional components on aging. Aging Cell 14, 8-16. https://doi.org/10.1111/acel.12277
  36. Lee, D., Jeong, D.E., Son, H.G., Yamaoka, Y., Kim, H., Seo, K., Khan, A.A., Roh, T.Y., Moon, D.W., Lee, Y., et al. (2015b). SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat. Genes Dev. 29, 2490-2503. https://doi.org/10.1101/gad.266304.115
  37. Lee, D., Son, H.G., Jung, Y., and Lee, S.V. (2017). The role of dietary carbohydrates in organismal aging. Cell. Mol. Life Sci. 74, 1793-1803. https://doi.org/10.1007/s00018-016-2432-6
  38. Lee, G.Y., Sohn, J., and Lee, S.V. (2021a). Combinatorial approach using Caenorhabditis elegans and mammalian systems for aging research. Mol. Cells 44, 425-432. https://doi.org/10.14348/molcells.2021.0080
  39. Lee, S.J., Hwang, A.B., and Kenyon, C. (2010). Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF1 activity. Curr. Biol. 20, 2131-2136. https://doi.org/10.1016/j.cub.2010.10.057
  40. Lee, S.J., Murphy, C.T., and Kenyon, C. (2009). Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab. 10, 379-391. https://doi.org/10.1016/j.cmet.2009.10.003
  41. Lee, Y., An, S.W.A., Artan, M., Seo, M., Hwang, A.B., Jeong, D.E., Son, H.G., Hwang, W., Lee, D., Seo, K., et al. (2015c). Genes and pathways that influence longevity in Caenorhabditis elegans. In Aging Mechanisms: Longevity, Metabolism, and Brain Aging, N. Mori and I. Mook-Jung, eds. (Tokyo, Japan: Springer), pp. 123-169.
  42. Lee, Y., Hwang, W., Jung, J., Park, S., Cabatbat, J.J., Kim, P.J., and Lee, S.J. (2016). Inverse correlation between longevity and developmental rate among wild C. elegans strains. Aging (Albany N.Y.) 8, 986-999.
  43. Lee, Y., Jung, Y., Jeong, D.E., Hwang, W., Ham, S., Park, H.H., Kwon, S., Ashraf, J.M., Murphy, C.T., and Lee, S.V. (2021b). Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop. J. Cell Biol. 220, e202006174. https://doi.org/10.1083/jcb.202006174
  44. Levine, B. and Kroemer, G. (2019). Biological functions of autophagy genes: a disease perspective. Cell 176, 11-42. https://doi.org/10.1016/j.cell.2018.09.048
  45. Li, Q., Hagberg, C.E., Silva Cascales, H., Lang, S., Hyvonen, M.T., Salehzadeh, F., Chen, P., Alexandersson, I., Terezaki, E., Harms, M.J., et al. (2021a). Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Nat. Med. 27, 1941-1953. https://doi.org/10.1038/s41591-021-01501-8
  46. Li, S.T., Zhao, H.Q., Zhang, P., Liang, C.Y., Zhang, Y.P., Hsu, A.L., and Dong, M.Q. (2019). DAF-16 stabilizes the aging transcriptome and is activated in mid-aged Caenorhabditis elegans to cope with internal stress. Aging Cell 18, e12896. https://doi.org/10.1111/acel.12896
  47. Li, W.J., Wang, C.W., Tao, L., Yan, Y.H., Zhang, M.J., Liu, Z.X., Li, Y.X., Zhao, H.Q., Li, X.M., He, X.D., et al. (2021b). Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans. Nat. Commun. 12, 4568. https://doi.org/10.1038/s41467-021-24816-z
  48. Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M., and Kroemer, G. (2013). The hallmarks of aging. Cell 153, 1194-1217. https://doi.org/10.1016/j.cell.2013.05.039
  49. Lykke-Andersen, S. and Jensen, T.H. (2015). Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes. Nat. Rev. Mol. Cell Biol. 16, 665-677. https://doi.org/10.1038/nrm4063
  50. Mack, H.I.D., Zhang, P., Fonslow, B.R., and Yates, J.R. (2017). The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans. Aging (Albany N.Y.) 9, 1414-1432.
  51. Martell, J., Seo, Y., Bak, D.W., Kingsley, S.F., Tissenbaum, H.A., and Weerapana, E. (2016). Global cysteine-reactivity profiling during impaired insulin/IGF-1 signaling in C. elegans identifies uncharacterized mediators of longevity. Cell Chem. Biol. 23, 955-966. https://doi.org/10.1016/j.chembiol.2016.06.015
  52. Melzer, D., Pilling, L.C., and Ferrucci, L. (2020). The genetics of human ageing. Nat. Rev. Genet. 21, 88-101. https://doi.org/10.1038/s41576-019-0183-6
  53. Mergoud Dit Lamarche, A., Molin, L., Pierson, L., Mariol, M.C., Bessereau, J.L., Gieseler, K., and Solari, F. (2018). UNC-120/SRF independently controls muscle aging and lifespan in Caenorhabditis elegans. Aging Cell 17, e12713. https://doi.org/10.1111/acel.12713
  54. Murphy, C.T., Lee, S.J., and Kenyon, C. (2007). Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A. 104, 19046-19050. https://doi.org/10.1073/pnas.0709613104
  55. 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. https://doi.org/10.1038/nature01789
  56. Narayan, V., Ly, T., Pourkarimi, E., Murillo, A.B., Gartner, A., Lamond, A.I., and Kenyon, C. (2016). Deep proteome analysis identifies age-related processes in C. elegans. Cell Syst. 3, 144-159. https://doi.org/10.1016/j.cels.2016.06.011
  57. Nieto-Torres, J.L. and Hansen, M. (2021). Macroautophagy and aging: the impact of cellular recycling on health and longevity. Mol. Aspects Med. 82, 101020. https://doi.org/10.1016/j.mam.2021.101020
  58. Orgel, L.E. (1963). The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc. Natl. Acad. Sci. U. S. A. 49, 517-521. https://doi.org/10.1073/pnas.49.4.517
  59. Park, H.H., Hwang, W., Ham, S., Kim, E., Altintas, O., Park, S., Son, H.G., Lee, Y., Lee, D., Heo, W.D., et al. (2021a). A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF1 signaling. Nat. Commun. 12, 5631. https://doi.org/10.1038/s41467-021-25920-w
  60. Park, H.H., Jung, Y., and Lee, S.V. (2017). Survival assays using Caenorhabditis elegans. Mol. Cells 40, 90-99. Park, S., Artan, M., Jeong, D.E., Park, H.H., Son, H.G., Kim, S.S., Jung, Y., https://doi.org/10.14348/molcells.2017.0017
  61. Choi, Y., Lee, J.I., Kim, K., et al. (2021b). Diacetyl odor shortens longevity conferred by food deprivation in C. elegans via downregulation of DAF16/FOXO. Aging Cell 20, e13300.
  62. Podshivalova, K., Kerr, R.A., and Kenyon, C. (2017). How a mutation that slows aging can also disproportionately extend end-of-life decrepitude. Cell Rep. 19, 441-450. https://doi.org/10.1016/j.celrep.2017.03.062
  63. Rodriguez, M., Snoek, L.B., De Bono, M., and Kammenga, J.E. (2013). Worms under stress: C. elegans stress response and its relevance to complex human disease and aging. Trends Genet. 29, 367-374. https://doi.org/10.1016/j.tig.2013.01.010
  64. Roy-Bellavance, C., Grants, J.M., Miard, S., Lee, K., Rondeau, E., Guillemette, C., Simard, M.J., Taubert, S., and Picard, F. (2017). The R148.3 gene modulates Caenorhabditis elegans lifespan and fat metabolism. G3 (Bethesda) 7, 2739-2747. https://doi.org/10.1534/g3.117.041681
  65. Senchuk, M.M., Dues, D.J., Schaar, C.E., Johnson, B.K., Madaj, Z.B., Bowman, M.J., Winn, M.E., and Van Raamsdonk, J.M. (2018). Activation of DAF16/FOXO by reactive oxygen species contributes to longevity in longlived mitochondrial mutants in Caenorhabditis elegans. PLoS Genet. 14, e1007268. https://doi.org/10.1371/journal.pgen.1007268
  66. Seo, M., Park, S., Nam, H.G., and Lee, S.J. (2016). RNA helicase SACY1 is required for longevity caused by various genetic perturbations in Caenorhabditis elegans. Cell Cycle 15, 1821-1829. https://doi.org/10.1080/15384101.2016.1183845
  67. Seo, M., Seo, K., Hwang, W., Koo, H.J., Hahm, J.H., Yang, J.S., Han, S.K., Hwang, D., Kim, S., Jang, S.K., et al. (2015). RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A. 112, E4246-E4255.
  68. Shin, D.W. (2020). Lipophagy: molecular mechanisms and implications in metabolic disorders. Mol. Cells 43, 686-693.
  69. Somogyvari, M., Gecse, E., and Soti, C. (2018). DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function. Sci. Rep. 8, 12048. https://doi.org/10.1038/s41598-018-30592-6
  70. Son, H.G., Altintas, O., Kim, E.J.E., Kwon, S., and Lee, S.V. (2019). Agedependent changes and biomarkers of aging in Caenorhabditis elegans. Aging Cell 18, e12853.
  71. Son, H.G., Seo, K., Seo, M., Park, S., Ham, S., An, S.W.A., Choi, E.S., Lee, Y., Baek, H., Kim, E., et al. (2018). Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegans. Genes Dev. 32, 1562-1575. https://doi.org/10.1101/gad.317362.118
  72. Son, H.G., Seo, M., Ham, S., Hwang, W., Lee, D., An, S.W., Artan, M., Seo, K., Kaletsky, R., Arey, R.N., et al. (2017). RNA surveillance via nonsensemediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans. Nat. Commun. 8, 14749. https://doi.org/10.1038/ncomms14749
  73. Soto, C. and Pritzkow, S. (2018). Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases. Nat. Neurosci. 21, 1332-1340. https://doi.org/10.1038/s41593-018-0235-9
  74. Sun, Y., Li, M., Zhao, D., Li, X., Yang, C., and Wang, X. (2020). Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans. Elife 9, e55745. https://doi.org/10.7554/eLife.55745
  75. Tawo, R., Pokrzywa, W., Kevei, E., Akyuz, M.E., Balaji, V., Adrian, S., Hohfeld, J., and Hoppe, T. (2017). The ubiquitin ligase CHIP integrates proteostasis and aging by regulation of insulin receptor turnover. Cell 169, 470-482.e13. https://doi.org/10.1016/j.cell.2017.04.003
  76. Tazearslan, C., Cho, M., and Suh, Y. (2012). Discovery of functional gene variants associated with human longevity: opportunities and challenges. J. Gerontol. A Biol. Sci. Med. Sci. 67, 376-383. https://doi.org/10.1093/gerona/glr200
  77. Uno, M., Tani, Y., Nono, M., Okabe, E., Kishimoto, S., Takahashi, C., Abe, R., Kurihara, T., and Nishida, E. (2021). Neuronal DAF-16-to-intestinal DAF16 communication underlies organismal lifespan extension in C. elegans. iScience 24, 102706. https://doi.org/10.1016/j.isci.2021.102706
  78. Venz, R., Pekec, T., Katic, I., Ciosk, R., and Ewald, C.Y. (2021). End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies. Elife 10, e71335. https://doi.org/10.7554/eLife.71335
  79. Visscher, M., De Henau, S., Wildschut, M.H.E., van Es, R.M., Dhondt, I., Michels, H., Kemmeren, P., Nollen, E.A., Braeckman, B.P., Burgering, B.M.T., et al. (2016). Proteome-wide changes in protein turnover rates in C. elegans models of longevity and age-related disease. Cell Rep. 16, 3041-3051. https://doi.org/10.1016/j.celrep.2016.08.025
  80. Wang, H., Webster, P., Chen, L., and Fisher, A.L. (2019). Cell-autonomous and non-autonomous roles of daf-16 in muscle function and mitochondrial capacity in aging C. elegans. Aging (Albany N.Y.) 11, 2295-2311.
  81. Williams, G.C. (2001). Pleiotropy, natural selection, and the evolution of senescence: Evolution 11, 398-411 (1957). Sci. Aging Knowledge Environ. 2001, cp13. https://doi.org/10.1126/sageke.2001.1.cp13
  82. Wolff, S., Weissman, J.S., and Dillin, A. (2014). Differential scales of protein quality control. Cell 157, 52-64. https://doi.org/10.1016/j.cell.2014.03.007
  83. Wu, M., Kang, X., Wang, Q., Zhou, C., Mohan, C., and Peng, A. (2017). Regulator of G protein signaling-1 modulates paraquat-induced oxidative stress and longevity via the insulin like signaling pathway in Caenorhabditis elegans. Toxicol. Lett. 273, 97-105. https://doi.org/10.1016/j.toxlet.2017.03.027
  84. Zaarur, N., Desevin, K., Mackenzie, J., Lord, A., Grishok, A., and Kandror, K.V. (2019). ATGL-1 mediates the effect of dietary restriction and the insulin/IGF-1 signaling pathway on longevity in C. elegans. Mol. Metab. 27, 75-82. https://doi.org/10.1016/j.molmet.2019.07.001
  85. Zecic, A., Dhondt, I., and Braeckman, B.P. (2022). Accumulation of glycogen and upregulation of LEA-1 in C. elegans daf-2(e1370) support stress resistance, not longevity. Cells 11, 245. https://doi.org/10.3390/cells11020245
  86. Zhang, Y., Zhang, W., and Dong, M. (2018). The miR-58 microRNA family is regulated by insulin signaling and contributes to lifespan regulation in Caenorhabditis elegans. Sci. China Life Sci. 61, 1060-1070. https://doi.org/10.1007/s11427-018-9308-8
  87. Zhou, K.I., Pincus, Z., and Slack, F.J. (2011). Longevity and stress in Caenorhabditis elegans. Aging (Albany N.Y.) 3, 733-753.
  88. Zhou, Y., Wang, X., Song, M., He, Z., Cui, G., Peng, G., Dieterich, C., Antebi, A., Jing, N., and Shen, Y. (2019). A secreted microRNA disrupts autophagy in distinct tissues of Caenorhabditis elegans upon ageing. Nat. Commun. 10, 4827. https://doi.org/10.1038/s41467-019-12821-2
  89. Zullo, J.M., Drake, D., Aron, L., O'Hern, P., Dhamne, S.C., Davidsohn, N., Mao, C.A., Klein, W.H., Rotenberg, A., Bennett, D.A., et al. (2019). Regulation of lifespan by neural excitation and REST. Nature 574, 359-364. https://doi.org/10.1038/s41586-019-1647-8