Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75.
The Caenorhabditis elegans homolog of mortalin/mthsp70/Grp75 (called mot-2 hereafter) was isolated by screening of a nematode cDNA library with mouse mot-2 cDNA. The isolated clone matched to hsp70F of C. elegans. Analysis with two of the antibodies raised against hsp70F revealed that unlike mammalian mot-2, it is heat inducible. Transient induction of hsp70F by heat shock led to a slight (<13%) extension in the C. elegans life span. The transgenic worms that constitutively over-expressed hsp70F predominantly in muscle showed life span extension (approximately 43% for mean and approximately 45% for maximum life span) as compared to the wild-type and green fluorescent protein-transgenic worms. Life span extension of human cells was obtained by over-expression of mot-2 [Kaul et al. (2000) FEBS Lett. 474, 159-164]. Our results show, for the first time, that this member of the hsp70 family governs the longevity of worms and thus there are common pathways that determine mammalian and worm longevity.
Yokoyama
Ken
K
Laboratory of Biochemistry, Department of Molecular and Cellular Biology, Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-0934, Ishikawa, Japan.
Fukumoto
Keiji
K
Murakami
Tatsuya
T
Harada
Shin-ichi
S
Hosono
Ryuji
R
Wadhwa
Renu
R
Mitsui
Youji
Y
Ohkuma
Shoji
S
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D017238:Genes, Helminth; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; C115087:Hspa9-ps1 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C018551:glucose-regulated proteins