title: Extended lifespan, reduced body size and leg skeletal muscle mass, and decreased mitochondrial function in clk-1 transgenic mice.
abstract: Mutational inactivation of clk-1, which encodes an enzyme necessary for the biosynthesis of coenzyme Q (CoQ), extends the lifespan of Caenorhabditis elegans. However, whether mammalian clk-1 regulates the lifespan of mice is not known because clk-1-deficiencies are embryonic lethal. Here, we investigated the lifespan of clk-1 transgenic mice (Tg96/I), which were rescued from embryonic lethality via the transgenic expression of mouse clk-1. Tg96/I mice lived longer and had smaller bodies than wild-type mice, but Tg96/I mice had CoQ levels equivalent to wild-type mice. The small-sized Tg96/I mice exhibited reduced whole-body oxygen consumption (VO2) during the dark period, and lean leg skeletal muscles with reduced mitochondrial VO2 and ATP content compared with wild-type mice. These findings indicate a close relationship between lifespan extension and decreased mitochondrial function, which was induced by the transgenic expression of clk-1, in leg skeletal muscles that exhibit high metabolic activity.
authors.affiliation: Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Animal Facility, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noda
authors.affiliation: Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Ikuroh
authors.initials: I
authors.lastname: Ohsawa
authors.affiliation: Department of Aging Control Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.affiliation: Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan. Electronic address: mmtaka@tmig.or.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D049628:Body Size / Q000235:genetics; D004734:Energy Metabolism; D005260:Female; D005838:Genotype; D008136:Longevity; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000201:enzymology*; D009929:Organ Size; D010101:Oxygen Consumption; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D052097:Quadriceps Muscle / Q000201:enzymology*; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D014451:Ubiquinone; D000255:Adenosine Triphosphate; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases
keywords: Coenzyme Q; Leg skeletal muscles; Lifespan; Mitochondrial function; Oxygen consumption; clk-1