Summary of Study ST001329
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 PR000908. The data can be accessed directly via it's Project DOI: 10.21228/M8B11Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001329 |
| Study Title | SS-31 and NMN: Two Paths to Improve Metabolism and Function in Aged Hearts |
| Study Summary | The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts. After treatment with the drugs, individually or Combined, heart function was examined by echocardiography. SS-31 partially reversed an age-related decline in diastolic function while NMN fully reversed an age-related deficiency in systolic function at a higher workload. Metabolomic analysis revealed that both NMN and the Combined treatment increased nicotinamide and 1-methylnicotinamide levels, indicating greater NAD+ turnover, but only the Combined treatment resulted in significantly greater steady state NAD(H) levels. A novel magnetic resonance approach was used to assess how metabolite levels responded to changing workload. PCr/ATP decreased in response to increased workload in Old Control, but not Young, hearts, indicating an age-related decline in energetic capacity. Both drugs were able to normalize the PCr/ATP dynamics. SS-31 and NMN treatment also increased mitochondrial NAD(P)H production under the higher workload while only NMN increased NAD+ in response to the work jump. These measures did not shift in hearts given the Combined treatment, which may be owed to the enhanced NAD(H) levels in the resting state after this treatment. Overall, these results indicate that both drugs are effective at restoring different aspects of mitochondrial and heart health and that combining them results in a synergistic effect that rejuvenates Old hearts and best recapitulates the Young state. |
| Institute | University of Washington |
| Last Name | Whitson |
| First Name | Jeremy |
| Address | 1959 NE Pacific St, Seattle, WA, 98195, USA |
| whitsonj@uw.edu | |
| Phone | 3307605189 |
| Submit Date | 2020-03-18 |
| Num Groups | 5 |
| Total Subjects | 53 |
| Num Males | 53 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-04-03 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000908 |
| Project DOI: | doi: 10.21228/M8B11Q |
| Project Title: | Metabolic Effects of SS-31 and NMN on Aged Mouse Hearts |
| Project Summary: | In this study we analyzed common metabolites in hearts taken from young mice and old mice that were either controls or treated with SS-31, NMN, or SS-31 + NMN. |
| Institute: | University of Washington |
| Last Name: | Whitson |
| First Name: | Jeremy |
| Address: | 1959 NE Pacific St, Seattle, WA, 98195, USA |
| Email: | whitsonj@uw.edu |
| Phone: | 3307605189 |
Subject:
| Subject ID: | SU001403 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | C57BL/6 |
| Age Or Age Range: | 5-6 months or 26 months |
| Animal Animal Supplier: | NIA |
| Animal Housing: | UW ARCF |
| Animal Feed: | Ad libitum |
| Animal Water: | Ad libitum |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Age (Months) | Treatment |
|---|---|---|---|
| SA096417 | JW45-NP | 26 | NMN (300 mg/kg/day) |
| SA096418 | JW45-LF | 26 | NMN (300 mg/kg/day) |
| SA096419 | JW44-RF | 26 | NMN (300 mg/kg/day) |
| SA096420 | JW39-RB | 26 | NMN (300 mg/kg/day) |
| SA096421 | JW46-LF | 26 | NMN (300 mg/kg/day) |
| SA096422 | JW51-LF | 26 | NMN (300 mg/kg/day) |
| SA096423 | JW46-RB | 26 | NMN (300 mg/kg/day) |
| SA096424 | JW33-LF | 26 | NMN (300 mg/kg/day) |
| SA096425 | JW27-LB | 26 | NMN (300 mg/kg/day) |
| SA096426 | JW29-LB | 26 | NMN (300 mg/kg/day) |
| SA096427 | JW39-RF | 26 | NMN (300 mg/kg/day) |
| SA096428 | JW49-LB | 26 | None |
| SA096429 | JW25-NP | 26 | None |
| SA096430 | JW25-R | 26 | None |
| SA096431 | JW48-NP | 26 | None |
| SA096432 | JW37-LB | 26 | None |
| SA096433 | JW41-RF | 26 | None |
| SA096434 | JW49-RF | 26 | None |
| SA096435 | JW42-LF | 26 | None |
| SA096436 | JW42-NP | 26 | None |
| SA096437 | JW43-RB | 26 | None |
| SA096438 | JW35-RF | 26 | SS-31 (3 mg/kg/day) |
| SA096439 | JW49-LF | 26 | SS-31 (3 mg/kg/day) |
| SA096440 | JW37-RB | 26 | SS-31 (3 mg/kg/day) |
| SA096441 | JW36-RF | 26 | SS-31 (3 mg/kg/day) |
| SA096442 | JW35-RB | 26 | SS-31 (3 mg/kg/day) |
| SA096443 | JW34-LB | 26 | SS-31 (3 mg/kg/day) |
| SA096444 | JW47-LF | 26 | SS-31 (3 mg/kg/day) |
| SA096445 | JW42-RF | 26 | SS-31 (3 mg/kg/day) |
| SA096446 | JW34-RF | 26 | SS-31 (3 mg/kg/day) |
| SA096447 | JW41-LF | 26 | SS-31 (3 mg/kg/day) |
| SA096448 | JW43-LB | 26 | SS-31 (3 mg/kg/day) |
| SA096449 | JW41-NP | 26 | SS-31 (3 mg/kg/day) |
| SA096450 | JW44-NP | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096451 | JW45-RF | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096452 | JW44-LF | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096453 | JW51-RF | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096454 | JW52-RF | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096455 | JW52-LF | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096456 | JW50-LF | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096457 | JW50-NP | 26 | SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day) |
| SA096458 | JWY1-LB | 5-6 | None |
| SA096459 | JWY1-RB | 5-6 | None |
| SA096460 | JWY2-RB | 5-6 | None |
| SA096461 | JWY4-RB | 5-6 | None |
| SA096462 | JWY4-LB | 5-6 | None |
| SA096463 | JWY1-RF | 5-6 | None |
| SA096464 | JWY4-LF | 5-6 | None |
| SA096465 | JWY4-RF | 5-6 | None |
| SA096466 | JWY2-LB | 5-6 | None |
| SA096467 | JWY2-LF | 5-6 | None |
| SA096468 | JWY2-RF | 5-6 | None |
| SA096469 | JWY1-LF | 5-6 | None |
| Showing results 1 to 53 of 53 |
Collection:
| Collection ID: | CO001398 |
| Collection Summary: | Hearts were removed from mice immediately following live cervical dislocation euthanasia. Hearts were flushed with sterile normal saline, cut into large chunks, and snap frozen in liquid nitrogen. |
| Sample Type: | Heart |
Treatment:
| Treatment ID: | TR001418 |
| Treatment Summary: | Mice were treated with SS-31, NMN, neither, or both for 8 weeks. SS-31 was administered through subdermal osmotic pumps at a 3 mg/kg body weight/day dose. NMN was administered through drinking water at a 300 mg/kg body weight/day dose. |
| Treatment Compound: | SS-31 and NMN |
| Treatment Route: | Subdermal osmotic pump for SS-31, drinking water for NMN |
| Treatment Dose: | 3 mg/kg body weight/day for SS-31, 300 mg/kg body weight/day for NMN |
Sample Preparation:
| Sampleprep ID: | SP001411 |
| Sampleprep Summary: | Heart tissue samples were homogenized in water and methanol with spiked stable isotopes as internal QC standards. Samples were purified by pelleting proteins, drying of the solution via Speedvac (Thermo Fisher Scientific), and reconstituting in HILIC solvent. |
Combined analysis:
| Analysis ID | AN002215 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Shimadzu Nexera XR LC-20AD |
| Column | Waters Acquity BEH Amide (150 x 2.1mm,1.7um) |
| MS Type | ESI |
| MS instrument type | Triple quadrupole |
| MS instrument name | ABI Sciex 6500 QTrap |
| Ion Mode | UNSPECIFIED |
| Units | Peak Area |
Chromatography:
| Chromatography ID: | CH001625 |
| Chromatography Summary: | Samples were injected into a chromatography system consisting of a dual injection valve setup allowing injections onto two different LC columns with each column dedicated to an ESI polarity. 5 µL were injected on the positive mode column and 10 µL on the negative side column. The columns were a matched pair from the same production lot number and were both a Waters XBridge BEH amide column (2.1 x 150 mm). Autosampler was maintained at 4 °C and column oven was set to 40 °C. 0.3 mL/min gradient was 0-3 min 95% B, 3-8 min 95 -> 50% B, 8-12 min 50% B, 12-13 min 50 – 95% B, 13-18 min 95% B. After completion of the 18 minute gradient, injection on the opposite column was initiated and the inactive column was allowed to equilibrate at starting gradient conditions. A set of QC injections for both instrument and sample QC were run at the beginning and end of the sample run. |
| Instrument Name: | Shimadzu Nexera XR LC-20AD |
| Column Name: | Waters Acquity BEH Amide (150 x 2.1mm,1.7um) |
| Column Temperature: | 40 |
| Solvent A: | 95% water/3% acetonitrile/2% methanol; 0.2% acetic acid; 10 mM ammonium acetate |
| Solvent B: | 93% acetonitrile/5% water/2% methanol; 0.2% acetic acid; 10 mM ammonium acetate |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS002061 |
| Analysis ID: | AN002215 |
| Instrument Name: | ABI Sciex 6500 QTrap |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| MS Comments: | Samples were injected into a chromatography system consisting of a dual injection valve setup allowing injections onto two different LC columns with each column dedicated to an ESI polarity. 5 µL were injected on the positive mode column and 10 µL on the negative side column. The columns were a matched pair from the same production lot number and were both a Waters XBridge BEH amide column (2.1 x 150 mm). Autosampler was maintained at 4 °C and column oven was set to 40 °C. 0.3 mL/min gradient was 0-3 min 95% B, 3-8 min 95 -> 50% B, 8-12 min 50% B, 12-13 min 50 – 95% B, 13-18 min 95% B. After completion of the 18 minute gradient, injection on the opposite column was initiated and the inactive column was allowed to equilibrate at starting gradient conditions. A set of QC injections for both instrument and sample QC were run at the beginning and end of the sample run. Data was integrated by MultiQuant 3.0.2 or Sciex-OS v1.5 software. Peaks were selected based on peak shape, a signal-to-noise of 10 or better and retention times consistent with previously run standards and sample sets. |
| Ion Mode: | UNSPECIFIED |
