title: Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats.
abstract: BACKGROUND
  The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle.
  
  
  METHODS
  15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student's t-test was performed to test the effect of the experimental conditions.
  
  
  RESULTS
  Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p < 0.01). Tibialis anterior weight was decreased in D-depleted rats (-25%, p < 0.05). The D-depleted group showed -39%, -31% drops in expression of two markers known to modulate proliferation (Bmp4, Fgf-2 mRNA levels) and -56% drop in one marker of cell proliferation (PCNA protein expression) compared to controls (p < 0.05). Notch pathway activity was blunted in tibialis anterior of D-depleted rats compared to controls, seen as a down-regulation of cleaved Notch (-53%, p < 0.05) and its target Hes1 (-35%, p < 0.05).
  
  
  CONCLUSIONS
  A 9-month vitamin D depletion induced vitamin D deficiency in old rats. Vitamin D depletion induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential. Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Carla
authors.initials: C
authors.lastname: Domingues-Faria
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Chanet
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Salles
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Berry
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Giraudet
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Patrac
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Installation Expérimentale de Nutrition, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Denis
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Bouton
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goncalves-Mendes
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; Centre Jean Perrin, Unité de Nutrition, 63000 Clermont-Ferrand, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Vasson
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; CHU Clermont-Ferrand, Service de Nutrition Clinique, 63003 Clermont-Ferrand, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Boirie
authors.affiliation: Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Walrand
keywords: Aging; Notch signalling; Skeletal muscle atrophy; Vitamin D deficiency