title: Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice.
abstract: Taurine (2-aminoethanesulfonic acid) is found in milimolar concentrations in mammalian tissues. One of its main functions is osmoregulation; however, it also exhibits cytoprotective activity by diminishing injury caused by stress and disease. Taurine depletion is associated with several defects, many of which are found in the aging animal, suggesting that taurine might exert anti-aging actions. Therefore, in the present study, we examined the hypothesis that taurine depletion accelerates aging by reducing longevity and accelerating aging-associated tissue damage. Tissue taurine depletion in taurine transporter knockout (TauTKO) mouse was found to shorten lifespan and accelerate skeletal muscle histological and functional defects, including an increase in central nuclei containing myotubes, a reduction in mitochondrial complex 1 activity and an induction in an aging biomarker, Cyclin-dependent kinase 4 inhibitor A (p16INK4a). Tissue taurine depletion also enhances unfolded protein response (UPR), which may be associated with an improvement in protein folding by taurine. Our data reveal that tissue taurine depletion affects longevity and cellular senescence; an effect possibly linked to a disturbance in protein folding.
authors.affiliation: College of Pharmacy, Department of Clinical Pharmacogenomics, Hyogo University of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.affiliation: College of Pharmacy, Department of Clinical Pharmacogenomics, Hyogo University of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Yoshikawa
authors.affiliation: College of Pharmacy, Department of Clinical Pharmacogenomics, Hyogo University of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Inui
authors.affiliation: College of Pharmacy, Department of Clinical Pharmacogenomics, Hyogo University of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Miyazaki
authors.affiliation: College of Medicine, Department of Pharmacology, University of South Alabama, Mobile, Alabama, United States of America.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Schaffer
authors.affiliation: College of Pharmacy, Department of Clinical Pharmacogenomics, Hyogo University of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D008017:Life Expectancy; D008136:Longevity; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency; D026901:Membrane Transport Proteins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010641:Phenotype; D013654:Taurine / Q000378:metabolism*; D056811:Unfolded Protein Response; D000099247:Taurine Transporters
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D000099247:Taurine Transporters