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.

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Study IDST001329
Study TitleSS-31 and NMN: Two Paths to Improve Metabolism and Function in Aged Hearts
Study SummaryThe 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 NameWhitson
First NameJeremy
Address1959 NE Pacific St, Seattle, WA, 98195, USA
Emailwhitsonj@uw.edu
Phone3307605189
Submit Date2020-03-18
Num Groups5
Total Subjects53
Num Males53
Raw Data AvailableYes
Raw Data File Type(s).wiff
Analysis Type DetailLC-MS
Release Date2020-04-03
Release Version1
Jeremy Whitson Jeremy Whitson
https://dx.doi.org/10.21228/M8B11Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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
SA096417JW45-NP26 NMN (300 mg/kg/day)
SA096418JW45-LF26 NMN (300 mg/kg/day)
SA096419JW44-RF26 NMN (300 mg/kg/day)
SA096420JW39-RB26 NMN (300 mg/kg/day)
SA096421JW46-LF26 NMN (300 mg/kg/day)
SA096422JW51-LF26 NMN (300 mg/kg/day)
SA096423JW46-RB26 NMN (300 mg/kg/day)
SA096424JW33-LF26 NMN (300 mg/kg/day)
SA096425JW27-LB26 NMN (300 mg/kg/day)
SA096426JW29-LB26 NMN (300 mg/kg/day)
SA096427JW39-RF26 NMN (300 mg/kg/day)
SA096428JW49-LB26 None
SA096429JW25-NP26 None
SA096430JW25-R26 None
SA096431JW48-NP26 None
SA096432JW37-LB26 None
SA096433JW41-RF26 None
SA096434JW49-RF26 None
SA096435JW42-LF26 None
SA096436JW42-NP26 None
SA096437JW43-RB26 None
SA096438JW35-RF26 SS-31 (3 mg/kg/day)
SA096439JW49-LF 26 SS-31 (3 mg/kg/day)
SA096440JW37-RB26 SS-31 (3 mg/kg/day)
SA096441JW36-RF26 SS-31 (3 mg/kg/day)
SA096442JW35-RB26 SS-31 (3 mg/kg/day)
SA096443JW34-LB26 SS-31 (3 mg/kg/day)
SA096444JW47-LF26 SS-31 (3 mg/kg/day)
SA096445JW42-RF26 SS-31 (3 mg/kg/day)
SA096446JW34-RF26 SS-31 (3 mg/kg/day)
SA096447JW41-LF26 SS-31 (3 mg/kg/day)
SA096448JW43-LB 26 SS-31 (3 mg/kg/day)
SA096449JW41-NP26 SS-31 (3 mg/kg/day)
SA096450JW44-NP26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096451JW45-RF26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096452JW44-LF26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096453JW51-RF 26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096454JW52-RF26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096455JW52-LF26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096456JW50-LF26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096457JW50-NP 26 SS-31 (3 mg/kg/day) + NMN (300 mg/kg/day)
SA096458JWY1-LB5-6 None
SA096459JWY1-RB5-6 None
SA096460JWY2-RB5-6 None
SA096461JWY4-RB5-6 None
SA096462JWY4-LB5-6 None
SA096463JWY1-RF5-6 None
SA096464JWY4-LF5-6 None
SA096465JWY4-RF5-6 None
SA096466JWY2-LB5-6 None
SA096467JWY2-LF5-6 None
SA096468JWY2-RF5-6 None
SA096469JWY1-LF5-6 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:10 mM ammonium acetate in 95% water, 3% acetonitrile, 2% methanol, and 0.2% acetic acid
Solvent B:10 mM ammonium acetate in 93% acetonitrile, 5% water, 2% methanol, and 0.2% acetic acid
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
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