Summary of Study ST003188

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 PR001984. The data can be accessed directly via it's Project DOI: 10.21228/M88J0W 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.

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Study IDST003188
Study TitleA metabolic atlas of mouse aging
Study SummaryHumans are living longer, but this is accompanied by an increased incidence of age-related chronic diseases. Many of these diseases are influenced by age-associated metabolic dysregulation, but how metabolism changes in multiple organs during aging in males and females is not known. Answering this could reveal new mechanisms of aging and age-targeted therapeutics. In this study, we describe how metabolism changes in 12 organs in male and female mice at 5 different ages. Organs show distinct patterns of metabolic aging that are affected by sex differently. Hydroxyproline shows the most consistent change across the dataset, decreasing with age in 11 out of 12 organs investigated. We also developed a metabolic aging clock that predicts biological age and identified alpha-ketoglutarate, previously shown to extend lifespan in mice, as a key predictor of age. Our results reveal fundamental insights into the aging process and identify new therapeutic targets to maintain organ health.
Institute
University of Southern California
DepartmentKeck School of Medicine
LaboratoryMullen Lab
Last NamePilley
First NameSteven
Address1501 San Pablo St., Los Angeles, CA, 90033, USA
Emailpilley@usc.edu
Phone+13234427555
Submit Date2024-05-02
Num Groups10
Total Subjects70
Num Males35
Num Females35
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-11-18
Release Version1
Steven Pilley Steven Pilley
https://dx.doi.org/10.21228/M88J0W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001984
Project DOI:doi: 10.21228/M88J0W
Project Title:A metabolic atlas of mouse aging
Project Summary:Humans are living longer, but this is accompanied by an increased incidence of age-related chronic diseases. Many of these diseases are influenced by age-associated metabolic dysregulation, but how metabolism changes in multiple organs during aging in males and females is not known. Answering this could reveal new mechanisms of aging and age-targeted therapeutics. In this study, we describe how metabolism changes in 12 organs in male and female mice at 5 different ages. Organs show distinct patterns of metabolic aging that are affected by sex differently. Hydroxyproline shows the most consistent change across the dataset, decreasing with age in 11 out of 12 organs investigated. We also developed a metabolic aging clock that predicts biological age and identified alpha-ketoglutarate, previously shown to extend lifespan in mice, as a key predictor of age. Our results reveal fundamental insights into the aging process and identify new therapeutic targets to maintain organ health.
Institute:University of Southern California
Department:Keck School of Medicine
Laboratory:Mullen Lab
Last Name:Pilley
First Name:Steven
Address:1501 San Pablo St., Los Angeles, CA, 90033, USA
Email:pilley@usc.edu
Phone:+13234427555
Funding Source:Impetus Grants 014746-00001

Subject:

Subject ID:SU003307
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6NCrl
Age Or Age Range:1-24 months
Gender:Male and female
Animal Animal Supplier:Charles River
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Age (months) Sex Organ
SA346837L55Bladder 18 Female Bladder
SA346838L56Bladder 18 Female Bladder
SA346839L54Bladder 18 Female Bladder
SA346840L53Bladder 18 Female Bladder
SA346841L50Bladder 18 Female Bladder
SA346842L51Bladder 18 Female Bladder
SA346843L52Bladder 18 Female Bladder
SA346844L19Bladder 18 Male Bladder
SA346845L21Bladder 18 Male Bladder
SA346846L18Bladder 18 Male Bladder
SA346847L20Bladder 18 Male Bladder
SA346848L17Bladder 18 Male Bladder
SA346849L15Bladder 18 Male Bladder
SA346850L16Bladder 18 Male Bladder
SA346851L39Bladder 1 Female Bladder
SA346852L41Bladder 1 Female Bladder
SA346853L40Bladder 1 Female Bladder
SA346854L38Bladder 1 Female Bladder
SA346855L42Bladder 1 Female Bladder
SA346856L36Bladder 1 Female Bladder
SA346857L37Bladder 1 Female Bladder
SA346858L1Bladder 1 Male Bladder
SA346859L7Bladder 1 Male Bladder
SA346860L6Bladder 1 Male Bladder
SA346861L5Bladder 1 Male Bladder
SA346862L4Bladder 1 Male Bladder
SA346863L2Bladder 1 Male Bladder
SA346864L3Bladder 1 Male Bladder
SA346865L59Bladder 21 Female Bladder
SA346866L58Bladder 21 Female Bladder
SA346867L60Bladder 21 Female Bladder
SA346868L61Bladder 21 Female Bladder
SA346869L63Bladder 21 Female Bladder
SA346870L57Bladder 21 Female Bladder
SA346871L62Bladder 21 Female Bladder
SA346872L23Bladder 21 Male Bladder
SA346873L25Bladder 21 Male Bladder
SA346874L24Bladder 21 Male Bladder
SA346875L28Bladder 21 Male Bladder
SA346876L26Bladder 21 Male Bladder
SA346877L27Bladder 21 Male Bladder
SA346878L22Bladder 21 Male Bladder
SA346879L64Bladder 24 Female Bladder
SA346880L70Bladder 24 Female Bladder
SA346881L69Bladder 24 Female Bladder
SA346882L68Bladder 24 Female Bladder
SA346883L67Bladder 24 Female Bladder
SA346884L65Bladder 24 Female Bladder
SA346885L66Bladder 24 Female Bladder
SA346886L35Bladder 24 Male Bladder
SA346887L34Bladder 24 Male Bladder
SA346888L29Bladder 24 Male Bladder
SA346889L33Bladder 24 Male Bladder
SA346890L32Bladder 24 Male Bladder
SA346891L30Bladder 24 Male Bladder
SA346892L31Bladder 24 Male Bladder
SA346893L47Bladder 3 Female Bladder
SA346894L46Bladder 3 Female Bladder
SA346895L48Bladder 3 Female Bladder
SA346896L49Bladder 3 Female Bladder
SA346897L44Bladder 3 Female Bladder
SA346898L43Bladder 3 Female Bladder
SA346899L45Bladder 3 Female Bladder
SA346900L9Bladder 3 Male Bladder
SA346901L8Bladder 3 Male Bladder
SA346902L14Bladder 3 Male Bladder
SA346903L10Bladder 3 Male Bladder
SA346904L13Bladder 3 Male Bladder
SA346905L12Bladder 3 Male Bladder
SA346906L11Bladder 3 Male Bladder
SA346907G solvent-2Blank NA NA NA
SA346908G solvent-1Blank NA NA NA
SA346909I solvent-1Blank NA NA NA
SA346910F solvent-2Blank NA NA NA
SA346911H solvent-2Blank NA NA NA
SA346912I solvent-2Blank NA NA NA
SA346913E solvent-1Blank NA NA NA
SA346914C solvent-2Blank NA NA NA
SA346915D solvent -1Blank NA NA NA
SA346916D solvent-2Blank NA NA NA
SA346917E solvent-2Blank NA NA NA
SA346918F solvent -1Blank NA NA NA
SA346919H solvent -1Blank NA NA NA
SA346920L solvent-2Blank NA NA NA
SA346921A solvent.d-1Blank NA NA NA
SA346922L solvent-1Blank NA NA NA
SA346923B solvent -1Blank NA NA NA
SA346924J solvent -1Blank NA NA NA
SA346925A solvent-2Blank NA NA NA
SA346926L solvent -1Blank NA NA NA
SA346927K solvent-1Blank NA NA NA
SA346928C solvent-1Blank NA NA NA
SA346929B solvent-2Blank NA NA NA
SA346930J solvent-2Blank NA NA NA
SA346931K solvent-2Blank NA NA NA
SA346932F53Brain 18 Female Brain
SA346933F56Brain 18 Female Brain
SA346934F52Brain 18 Female Brain
SA346935F55Brain 18 Female Brain
SA346936F51Brain 18 Female Brain
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Collection:

Collection ID:CO003300
Collection Summary:We purchased male and virgin female C57BL/6NCrl mice from Charles River (RRID:IMSR_CRL:027) and housed them at USC. Mice were housed under identical conditions at both Charles River and USC (12 hr/12 hr light dark cycle) and fed the same diet ad libitum (NIH-31 diet). The 1-month-old, 3-month-old, and 18-month-old mice were kept at USC for one week before harvesting. The 21-month-old and 24-month-old mice arrived aged 18 months and were aged at USC for the remaining 3 months and 6 months respectively. All tissues were collected beginning at 3 pm on each day of harvest. We used 4% isoflurane to anaesthetize the mice. We then weighed the mice and collected blood via cardiac puncture into EDTA collection tubes and placed them on ice. We then collected organs in the following order: heart, thymus, lungs, liver, pancreas, spleen, kidney, bladder, quadriceps muscle, tongue, and brain. The organs were immediately snap frozen in liquid nitrogen and stored at -80C until metabolite extraction. Organ collection finished by 5 pm. All animal care and procedures were approved by the USC Department of Animal Research.
Sample Type:Blood (plasma), heart, pancreas, liver, kidney, brain, spleen, quadriceps muscle, lung, thymus, tongue, bladder

Treatment:

Treatment ID:TR003316
Treatment Summary:We purchased male and virgin female C57BL/6NCrl mice from Charles River (RRID:IMSR_CRL:027) and housed them at USC. Mice were housed under identical conditions at both Charles River and USC (12 hr/12 hr light dark cycle) and fed the same diet ad libitum (NIH-31 diet). The 1-month-old, 3-month-old, and 18-month-old mice were kept at USC for one week before harvesting. The 21-month-old and 24-month-old mice arrived aged 18 months and were aged at USC for the remaining 3 months and 6 months respectively.

Sample Preparation:

Sampleprep ID:SP003314
Sampleprep Summary:To obtain plasma, we centrifuged EDTA-tubes containing blood at 4°C at 2,000 g for 15 minutes. We collected supernatants and added 20 μL to 80 μL 100% LC-grade methanol. For tissue homogenization, we put tissue samples in 10 μL ice-cold 4:1 LC-grade Methanol:Ultrapure-water per mg tissue and homogenized them using a bead homogenizer (Bead Mill 4, Fisherbrand). We centrifuged plasma supernatants and tissue homogenates at 4°C at 21,300 g for 10 minutes and collected the metabolite-containing supernatants. We dried down 100 μL of supernatant from each sample (equivalent to 10 mg of tissue) using a vacuum centrifuge and stored them at -80°C until further processing. Dried supernatants reconstituted in 50ul of LC-grade Methanol: Ultrapure-water mix (1:1) and then analyzed using the Agilent 1290 Infinity II LC –6470 Triple Quadrupole (QqQ) tandem mass spectrometer (MS/MS).

Chromatography:

Chromatography ID:CH003963
Instrument Name:Agilent 1290 Infinity II
Column Name:Agilent ZORBAX RRHD SB-C18 (150 x 2.1mm,1.8um)
Column Temperature:35
Flow Gradient:0.25 mL/min, 0–2.5 min, 100% A; 7.5 min, 80% A and 20% B; 13 min 55% A and 45% B; 20 min, 1% A and 99% B; 24 min, 1% A and 99% B; 24.05 min, 1% A and 99% C; 27 min, 1% A and 99% C; at 0.8 mL/min, 27.5–31.35 min, 1% A and 99% C; at 0.6 mL/min, 31.50 min, 1% A and 99% C; at 0.4 mL/min, 32.25–39.9 min, 100% A; and at 0.25 mL/min, 40 min, 100% A.
Flow Rate:0.25-0.8 mL/min
Solvent A:97% water/3% methanol;15 mM acetic acid; 10 mM tributylamine at pH 5
Solvent B:100% methanol; 15 mM acetic acid; 10 mM tributylamine
Chromatography Type:Reversed phase
Solvent C:100% acetonitrile, wash solvent.

Analysis:

Analysis ID:AN005236
Laboratory Name:Lyssiotis Lab
Analysis Type:MS
Operator Name:Li Zhang
Chromatography ID:CH003963
Num Factors:133
Num Metabolites:190
Units:AU
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