Tier 3 — preclinical

Old mitochondria regulate niche renewal via α-ketoglutarate metabolism in stem cells

Andersson S, Bui H, Viitanen A, Borshagovski D, Salminen E, Kilpinen S, Gebhart A, Kuuluvainen E, Gopalakrishnan S, Peltokangas N, James M, Achim K, Jokitalo E, Auvinen P, Hietakangas V, Katajisto P
Nature Metabolism 2025 7(7):1344-1357

Bibliography

PubMed
PMID 40659911
PubMed Central
PMC12286850
DOI
10.1038/s42255-025-01325-7
Funding
Academic funding is reported in the Nature Metabolism article.
Competing interests
The authors declared no competing interests.

Study snapshot

DesignMechanistic intestinal stem-cell and organoid study with in-vivo supplementation in aged mice.
ModelMouse intestinal stem cells, organoids and aged mice recovering from chemotherapy-induced intestinal damage.
SampleMultiple cell, organoid and mouse cohorts; group sizes vary by experiment.
InterventionAlpha-ketoglutarate supplementation in aged mice plus mechanistic manipulation of mitochondrial age and TET-linked signaling.
DurationStudy-specific niche-renewal and chemotherapy-recovery experiments.
EndpointsPaneth-cell niche renewal; Intestinal stem-cell fate; AKG metabolism; TET-dependent epigenetic change; Recovery from chemotherapy-induced injury

What the study showed, in plain terms

This Nature Metabolism study shows how mitochondrial age can influence stem-cell fate through AKG metabolism.

A subset of intestinal stem cells containing older mitochondria produced more AKG and used TET-dependent epigenetic signaling to rebuild the Paneth-cell niche. In aged mice, AKG supplementation enhanced niche renewal and improved recovery after chemotherapy-induced damage.

It is high-quality aging/stem-cell evidence, but the outcome is tissue regeneration in mice rather than human longevity or supplement efficacy.

Key findings

  • Old-mitochondria-enriched intestinal stem cells produced more AKG.
  • AKG drove TET-mediated epigenetic changes favoring Paneth-cell niche formation.
  • AKG supplementation enhanced niche turnover and recovery after chemotherapy damage in aged mice.

What this study can and cannot tell us

  • Preclinical mouse study.
  • The injury/recovery model is not equivalent to routine supplementation in healthy adults.
  • No clinical Ca-AKG outcomes were measured.

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