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

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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
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