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.
References
48
Referenced
822
10.1093/jn/10.1.63
- 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)
10.1152/ajpendo.1995.268.5.E941
10.1007/s11357-997-0004-2
10.1093/jn/127.12.2293
10.1152/ajpendo.1997.273.4.E714
10.1016/S0031-9384(97)00147-9
10.1126/science.273.5271.59
10.1016/0891-5849(96)00162-1
10.1002/jcp.1030650313
10.3109/07420529009056963
10.1073/pnas.93.9.4159
10.1152/ajpendo.1985.248.4.E488
- E J Masoro, R J M McCarter Aging (Milano) 2, 117–128 (1991). / Aging (Milano) by Masoro E J (1991)
- 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)
10.1152/ajpendo.1997.272.5.E901
- M R Rose Evolutionary Biology of Aging (Oxford Univ. Press, New York, 1991). / Evolutionary Biology of Aging by Rose M R (1991)
10.1016/S0960-9822(94)00036-9
10.1126/science.273.5271.54
10.1016/S0168-9525(97)01299-7
10.1038/382536a0
10.1126/science.277.5328.942
10.1126/science.278.5341.1319
10.1038/40194
10.1093/genetics/137.1.107
10.1038/366461a0
10.1093/genetics/139.4.1567
10.1093/genetics/141.4.1399
10.1093/genetics/139.3.1247
10.1126/science.272.5264.1010
10.1126/science.275.5302.980
10.1016/0047-6374(77)90043-4
10.1016/0531-5565(89)90016-8
10.1093/genetics/133.4.897
10.1093/genetics/141.4.1365
10.1523/JNEUROSCI.15-12-08408.1995
10.1083/jcb.134.2.537
10.1093/emboj/16.20.6066
10.1093/genetics/141.4.1351
10.1093/genetics/77.1.71
- 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)
10.1093/jn/116.4.641
- 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)
- 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)
10.1093/genetics/143.3.1207
10.1093/genetics/143.3.1193
10.1074/jbc.271.6.2995
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) |
@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} }