Endogenously determined restriction of food intake overcomes excitation–contraction uncoupling in JP45KO mice with aging

Delbono, Osvaldo and Messi, Maria Laura and Wang, Zhong-Min and Treves, Susan and Mosca, Barbara and Bergamelli, Leda and Nishi, Miyuki and Takeshima, Hiroshi and Shi, Hang and Xue, Bingzhong and Zorzato, Francesco. (2012) Endogenously determined restriction of food intake overcomes excitation–contraction uncoupling in JP45KO mice with aging. Experimental Gerontology, 47 (4). pp. 304-316.

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The decline in muscular strength with age is disproportionate to the loss in total muscle mass that causes it. Knocking out JP45, an integral protein of the junctional face membrane of the skeletal muscle sarcoplasmic reticulum (SR), results in decreased expression of the voltage-gated Ca2 + channel, Cav1.1; excitation–contraction uncoupling (ECU); and loss of muscle force (Delbono et al., 2007). Here, we show that Cav1.1 expression, charge movement, SR Ca2 + release, in vitro contractile force, and sustained forced running remain stable in male JP45KO mice at 12 and 18 months. They also exhibit the level of ECU reported for 3–4-month mice (Delbono et al., 2007). No further decline at later ages was recorded. Preserved ECC was not related to increased expression of any protein that directly or indirectly interacts with JP45 at the triad junction. However, maintained muscle force and physical performance were associated with ablation of JP45 expression in the brain, spontaneous and significantly diminished food intake and less tendency toward obesity when exposed to a high-fat diet compared to WT. We propose that (1) endogenously generated restriction in food intake overcomes the deleterious effects of JP45 ablation on ECC and skeletal muscle force mainly through downregulation of neuropeptide-Y expression in the hypothalamic arcuate nucleus; and (2) the JP45KO mouse constitutes an invaluable model to examine the mechanisms controlling food intake as well as skeletal muscle function with aging.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Perioperative Patient Safety (Girard/Treves)
UniBasel Contributors:Treves, Susan and Zorzato, Francesco
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 May 2017 09:21
Deposited On:04 May 2017 07:01

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