Summary of Study ST003703
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002298. The data can be accessed directly via it's Project DOI: 10.21228/M8KR8S This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003703 |
| Study Title | NAD Depletion in Skeletal Muscle does not Compromise Muscle Function or Accelerate Aging |
| Study Summary | NAD is a ubiquitous electron carrier essential for energy metabolism and the posttranslational modification of numerous regulatory proteins. Perturbation of NAD metabolism is considered detrimental to health, with NAD depletion commonly thought to promote aging. However, the extent to which cellular NAD concentration can be decreased without deleterious repercussions is unclear. We generated a mouse model where nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis is disrupted in adult skeletal muscle. The resulting 85% decrease in muscle NAD+ abundance was associated with preserved tissue integrity and functionality, as demonstrated by its unchanged morphology, contractility, and exercise tolerance. This lack of defects was corroborated by intact mitochondrial respiratory capacity and unaffected muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings indicate that NAD depletion does not contribute to agerelated declines in skeletal muscle function. |
| Institute | University of Copenhagen |
| Last Name | Treebak |
| First Name | Jonas Thue |
| Address | Blegdamsvej 3B, Mærsk Tårnet, 7. sal 2200 København N. |
| jttreebak@sund.ku.dk | |
| Phone | +4524805398 |
| Submit Date | 2025-02-03 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-02-24 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO003828 |
| Collection Summary: | All animal experiments were performed following the European directive 2010/63/EU of the European Parliament and the Council of the protection of animals used for scientific purposes, approved by the Danish Animal Experiments Inspectorate (license numbers: 2015-15-0201-00796, 2018-15-0201-01493, 2020-15-0201-00764). Previously generated homozygous Nampt-floxed carrying mice (Nampttm1Jtree) were crossed with animals heterozygous for the inducible human α-skeletal actin promoter-driven MCM Cre (HSACreMCM), so that the target transgenic strain HSACreMCM-Nampttm1Jtree was obtained after crossing with Nampttm1Jtree. After induction, Cre-/+ mice were knockouts (i.e., iSMNKO), while the Cre-/- littermates were used as controls. All animals used in the experiments were on a C57BL/6JBomTac background (Taconic, Denmark). Both iSMNKO and control animals at the age of 9-15 weeks were dosed orally with 2 mg/day of tamoxifen (Sigma-Aldrich T5648) suspended in corn oil (Sigma-Aldrich C8267) for three consecutive days. All animals were housed in standard conditions with controlled temperature (22 ± 1ºC) and a 12 h light-dark cycle and received water and chow diet (Altromin 1310 or equivalent SAFE DS D30) ad libitum. Experiments were performed on male 16-25-week-old mice unless stated otherwise Briefly, SOL and EDL muscles were obtained from 23-week-old (12 weeks after tamoxifen) control and mutant animals anaesthetized with an intraperitoneal injection of Avertin (2,2,2-Tribromoehtanol and 2- methyl-2-butanol (Sigma Aldrich #T48402 and #152463))Mitochondria isolation Mitochondrial fraction was isolated from muscle tissue with nagarse digestion and differential centrifugation, as previously described46. Briefly, 100 mg of the freshly dissected muscle tissue was homogenized after crude mechanical and enzymatic digestion. Followed by two centrifugation steps, the mitochondria-enriched pellet was washed, resuspended, and its protein content was determined with the Bradford method (BioRad #5000205). After the final centrifugation, the mitochondrial pellet was either snap-frozen in liquid nitrogen or suspended in an appropriate assay buffer. When a large quantity of the mitochondrial material was required (more than 250 µg), isolation was performed on up to 1 g of muscle tissue per isolation round, with the according upscaling of the reagents’ volumes. |
| Sample Type: | Biopsy |
