Tier 2 — strong

Alpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives

Hakimi Naeini S, Mavaddatiyan L, Rashid Kalkhoran Z, Taherkhani S, Talkhabi M
Experimental Gerontology 2023 175:112154

Bibliography

PubMed
PMID 36934991
DOI
10.1016/j.exger.2023.112154
Funding
Funding information is not prominent in the PubMed record reviewed for this entry.
Competing interests
The authors declared no conflict of interest.

Study snapshot

DesignNarrative review of AKG aging, lifespan, stem-cell, reproductive and mechanistic evidence.
ModelPublished cell, animal and human literature.
SampleNot applicable — narrative review.
InterventionNot applicable.
DurationNot applicable.
EndpointsLifespan and healthspan evidence; mTOR and ATP synthase mechanisms; Epigenetic regulation; Stem-cell biology; Reproductive aging; Cancer biology

What the study showed, in plain terms

This 2023 review is a dedicated synthesis of AKG's proposed roles in lifespan and healthspan.

It brings together model-organism longevity studies, stem-cell biology, reproductive aging, epigenetics and metabolic signaling, making it useful as a navigation paper for the Ca-AKG corpus.

Because it predates the 2024 and 2026 NIA ITP null lifespan studies, its positive longevity framing must now be read alongside those later replication failures.

Key findings

  • The review summarizes AKG effects across lifespan, reproduction, stem-cell and metabolic models.
  • Mechanisms discussed include mTOR and ATP synthase modulation, ROS biology and DNA/histone demethylation.
  • It identifies AKG as a promising aging metabolite while acknowledging translational limitations.

What this study can and cannot tell us

  • Narrative review rather than systematic review or meta-analysis.
  • Published before the two NIA ITP null-lifespan AKG papers now in this Data Center.
  • Review-level conclusions cannot replace primary human efficacy evidence.

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