Evidence map›Paper›PMID 40410187›Full record

Articlenpj aging2025

Metabolomics biomarkers of frailty: a longitudinal study of aging female and male mice.

Dantong Zhu, Judy Z Wu, Patrick T Griffin, Brady A Samuelson, David A Sinclair, Alice E Kane

Abstract read
In one paragraph

Article in npj aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Dantong ZhuInstitute for Systems Biology, Seattle, WA, USA.
Judy Z WuInstitute for Systems Biology, Seattle, WA, USA.
Patrick T GriffinBlavatnik Institute, Department of Genetics, Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, Boston, MA, USA.
Brady A SamuelsonInstitute for Systems Biology, Seattle, WA, USA.
David A SinclairBlavatnik Institute, Department of Genetics, Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, Boston, MA, USA.
Alice E KaneInstitute for Systems Biology, Seattle, WA, USA. alice.kane@isbscience.org.

Funding

Role of Sgs1 DNA helicase in telomere maintenanceR01AG019719 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SINCLAIR, DAVID A. · 2001 to 2022
$5.3M
Development of a Predictive Frailty Clock & Longitudinal Investigation of its Epigenetic DeterminantsR00AG070102 · NIA · INSTITUTE FOR SYSTEMS BIOLOGY · PI KANE, ALICE E · 2023 to 2025
$1.0M
Tagmentation-based Indexing for Methylation Sequencing as a novel method of high-throughput methylation clock measurementR21HG011850 · NHGRI · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2021 to 2021
$626k
A novel method to identify regulators of biological aging 
based on high-throughput sequencing of epigenetic clocks.K00AG073499 · NIA · HARVARD UNIVERSITY · PI Patrick Griffin · 2023 to 2026
$304k
NHGRI NIH HHS R21 HG011850NIA NIH HHS K00 AG073499NIA NIH HHS R00 AG070102NIA NIH HHS R00AG070102NIA NIH HHS R01 AG019719NIA NIH HHS R01AG019719
6 · The paper itself

Abstract

Frailty is an age-related geriatric syndrome. We performed a longitudinal study of aging female (n = 40) and male (n = 47) C57BL/6NIA mice, measured frailty index and derived metabolomics data from plasma. We identify age-related differentially abundant metabolites, determine frailty-related metabolites, and generate frailty features, both in the whole cohort and sex-stratified subgroups. Using the features, we perform an association study and build a metabolomics-based frailty clock. We find that frailty-related metabolites are enriched for amino acid metabolism and metabolism of cofactors and vitamins, include ergothioneine, tryptophan and alpha-ketoglutarate, and present sex dimorphism. We identify B vitamin metabolism related flavin-adenine dinucleotide and pyridoxate as female-specific frailty biomarkers, and lipid metabolism related sphingomyelins, glycerophosphoethanolamine and glycerophosphocholine as male-specific frailty biomarkers. These associations are confirmed in a validation cohort, with ergothioneine and perfluorooctanesulfonate identified as robust frailty biomarkers. Our results identify sex-specific metabolite frailty biomarkers, and shed light on potential mechanisms.

Identifiers

PMID40410187
PMCPMC12102153

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.