Mutations that increase the life span of C. elegans inhibit tumor growth.
Mutations in gld-1 cause lethal germline tumors in the nematode Caenorhabditis elegans. We find that a wide variety of mutations that extend C. elegans' life span confer resistance to these tumors. The long life spans of daf-2/insulin-receptor mutants were not shortened at all by gld-1 mutations; we attribute this finding to decreased cell division and increased DAF-16/p53-dependent apoptosis within the tumors. Mutations that increase life span by restricting food intake or inhibiting respiration did not affect apoptosis but reduced tumor cell division. Unexpectedly, none of these longevity mutations affected mitosis in normal germlines; this finding suggests that cellular changes that lead to longevity preferentially antagonize tumor cell growth.
Pinkston
Julie M
JM
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
Garigan
Delia
D
Hansen
Malene
M
Kenyon
Cynthia
C
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D031204:Caloric Restriction; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors; D017238:Genes, Helminth; D005854:Germ Cells / Q000166:cytology; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D009866:Oogenesis; D011972:Receptor, Insulin / Q000235:genetics* / Q000502:physiology; D012098:Reproduction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C094448:GLD-1 protein, C elegans; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin