Tier 4 — mechanistic

Identifying the target, mechanism, and agonist of α-ketoglutaric acid in delaying mesenchymal stem cell senescence

Cui Z, Li J, Li C, Deng S, Liu W, Lei T, Cao J, Wang Z, Wang X, Ma S, Zhu Y, Yang H, Chen P
Cell Reports 2025 44(7):115917

Bibliography

PubMed
PMID 40570373
DOI
10.1016/j.celrep.2025.115917
Funding
Funding details should be read in the full Cell Reports article; the accessible record confirms a multi-institution academic study.
Competing interests
One author affiliation includes AstraZeneca Pharmaceuticals; the accessible PubMed record does not establish Ca-AKG supplement-company sponsorship.

Study snapshot

DesignMechanistic mesenchymal stem-cell study with aged-mouse validation of an AKG-raising IDH1 agonist.
ModelMesenchymal stem cells plus aged C57BL mice; direct exogenous AKG effects were principally tested at the cellular level.
SampleMultiple cell and mouse experiments; group size varied by assay.
InterventionExogenous AKG or IDH1 manipulation in cells; scutellarin used in aged mice to raise endogenous AKG.
DurationStudy-specific cell and aged-mouse treatment periods.
EndpointsMSC senescence; IDH1 activity and AKG levels; OGFOD1-mediated RPS23 hydroxylation; Translation fidelity; Proteostasis; Age-related mouse phenotypes

What the study showed, in plain terms

This 2025 Cell Reports paper investigated why falling AKG may matter to stem-cell aging.

The authors linked lower IDH1 expression and reduced AKG to mesenchymal stem-cell senescence. Restoring AKG in cells enhanced OGFOD1-dependent RPS23 hydroxylation and improved translation fidelity and proteostasis.

Aged-mouse experiments used scutellarin to raise endogenous AKG rather than oral Ca-AKG, so this paper is mechanistic support rather than supplement-efficacy evidence.

Key findings

  • Lower IDH1 expression reduced AKG and accelerated MSC senescence.
  • Exogenous AKG improved OGFOD1-RPS23 signaling and translation fidelity in cells.
  • Raising endogenous AKG with scutellarin improved several age-related phenotypes in mice.

What this study can and cannot tell us

  • Direct AKG supplementation was primarily a cell-culture intervention.
  • The in-vivo arm used scutellarin, not Ca-AKG.
  • No human oral supplementation or clinical outcomes were studied.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology