Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans. To understand better how caloric restriction lengthens life span, we used genetic methods and criteria to investigate its mechanism of action in the nematode Caenorhabditis elegans . Mutations in many genes ( eat genes) result in partial starvation of the worm by disrupting the function of the pharynx, the feeding organ. We found that most eat mutations significantly lengthen life span (by up to 50%). In C. elegans, mutations in a number of other genes that can extend life span have been found. Two genetically distinct mechanisms of life span extension are known: a mechanism involving genes that regulate dauer formation ( age-1, daf-2, daf-16 , and daf-28 ) and a mechanism involving genes that affect the rate of development and behavior ( clk-1, clk-2, clk-3 , and gro-1 ). We find that the long life of eat-2 mutants does not require the activity of DAF-16 and that eat-2; daf-2 double mutants live even longer than extremely long-lived daf-2 mutants. These findings demonstrate that food restriction lengthens life span by a mechanism distinct from that of dauer-formation mutants. In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes.

Bibliography

Lakowski, B., & Hekimi, S. (1998). The genetics of caloric restriction in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, 95(22), 13091–13096.

Authors 2
  1. Bernard Lakowski (first)
  2. Siegfried Hekimi (additional)
References 48 Referenced 822
  1. 10.1093/jn/10.1.63
  2. R K Weindruch, R L Walford The Retardation of Aging and Disease by Dietary Restriction. (Thomas, Springfield, IL, 1988). / The Retardation of Aging and Disease by Dietary Restriction. by Weindruch R K (1988)
  3. 10.1152/ajpendo.1995.268.5.E941
  4. 10.1007/s11357-997-0004-2
  5. 10.1093/jn/127.12.2293
  6. 10.1152/ajpendo.1997.273.4.E714
  7. 10.1016/S0031-9384(97)00147-9
  8. 10.1126/science.273.5271.59
  9. 10.1016/0891-5849(96)00162-1
  10. 10.1002/jcp.1030650313
  11. 10.3109/07420529009056963
  12. 10.1073/pnas.93.9.4159
  13. 10.1152/ajpendo.1985.248.4.E488
  14. E J Masoro, R J M McCarter Aging (Milano) 2, 117–128 (1991). / Aging (Milano) by Masoro E J (1991)
  15. A G Dulloo, L Girardier Int J Obes Relat Metab Disord 17, 115–123 (1993). / Int J Obes Relat Metab Disord by Dulloo A G (1993)
  16. 10.1152/ajpendo.1997.272.5.E901
  17. M R Rose Evolutionary Biology of Aging (Oxford Univ. Press, New York, 1991). / Evolutionary Biology of Aging by Rose M R (1991)
  18. 10.1016/S0960-9822(94)00036-9
  19. 10.1126/science.273.5271.54
  20. 10.1016/S0168-9525(97)01299-7
  21. 10.1038/382536a0
  22. 10.1126/science.277.5328.942
  23. 10.1126/science.278.5341.1319
  24. 10.1038/40194
  25. 10.1093/genetics/137.1.107
  26. 10.1038/366461a0
  27. 10.1093/genetics/139.4.1567
  28. 10.1093/genetics/141.4.1399
  29. 10.1093/genetics/139.3.1247
  30. 10.1126/science.272.5264.1010
  31. 10.1126/science.275.5302.980
  32. 10.1016/0047-6374(77)90043-4
  33. 10.1016/0531-5565(89)90016-8
  34. 10.1093/genetics/133.4.897
  35. 10.1093/genetics/141.4.1365
  36. 10.1523/JNEUROSCI.15-12-08408.1995
  37. 10.1083/jcb.134.2.537
  38. 10.1093/emboj/16.20.6066
  39. 10.1093/genetics/141.4.1351
  40. 10.1093/genetics/77.1.71
  41. J Sultson, J Hodgkin The Nematode Caenorhabditis elegans, ed W B Wood (Cold Spring Harbor Lab. Press, Plainview, NY), pp. 587–606 (1988). / The Nematode Caenorhabditis elegans by Sultson J (1988)
  42. 10.1093/jn/116.4.641
  43. M Chalfie, J White The Nematode Caenorhabditis elegans, ed W B Wood (Cold Spring Harbor Lab. Press, Plainview, NY,), pp. 337–391 (1988). / The Nematode Caenorhabditis elegans by Chalfie M (1988)
  44. T E Johnson Invertebrate Models in Aging Research, eds D H Mitchell, T E Johnson (CRC, Boca Raton, FL), pp. 59–93 (1984). / Invertebrate Models in Aging Research by Johnson T E (1984)
  45. 10.1093/genetics/143.3.1207
  46. 10.1093/genetics/143.3.1193
  47. 10.1074/jbc.271.6.2995
  48. 10.1074/jbc.273.6.3351
Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited 3 years, 4 months ago (April 13, 2022, 4:06 p.m.)
Indexed 21 hours, 14 minutes ago (Sept. 4, 2025, 9:36 a.m.)
Issued 26 years, 10 months ago (Oct. 27, 1998)
Published 26 years, 10 months ago (Oct. 27, 1998)
Published Online 26 years, 10 months ago (Oct. 27, 1998)
Published Print 26 years, 10 months ago (Oct. 27, 1998)
Funders 0

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@article{Lakowski_1998, title={The genetics of caloric restriction in Caenorhabditis elegans}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.22.13091}, DOI={10.1073/pnas.95.22.13091}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lakowski, Bernard and Hekimi, Siegfried}, year={1998}, month=oct, pages={13091–13096} }