Tier 3 — preclinical

α-ketoglutarate delays age-related fertility decline in mammals

Zhang Z, He C, Gao Y, Zhang L, Song Y, Zhu T, Zhu K, Lv D, Wang J, Tian X, Ma T, Ji P, Cui W, Liu G
Aging Cell 2021 20(2):e13291

Bibliography

PubMed
PMID 33450127
PubMed Central
PMC7884030
DOI
10.1111/acel.13291
Funding
Guoshi Liu was supported by the National Natural Science Foundation of China (31830091), Beijing Dairy Industry Innovation Team (BAIC06-2017), National New Biological Breeding Project (2018ZX08008-01B), and the National Science and Technology Major Project of China (2016ZX08008003).
Competing interests
The authors declared no conflict of interest that could be perceived as prejudicing the impartiality of the research.

Study snapshot

DesignCross-species aging study combining human and swine observational measurements with long-term mouse intervention.
ModelHuman follicular fluid observations, swine reproductive-aging observations and aging mice.
SampleMultiple cross-species cohorts; exact group sizes vary by experiment.
InterventionLong-term alpha-ketoglutarate administration in aging mice.
DurationLong-term mouse supplementation; study-specific durations are reported in the full paper.
EndpointsOvarian function; Oocyte quantity and quality; Fertility; Telomere maintenance; mTOR signaling; Follicular-fluid AKG

What the study showed, in plain terms

This cross-species study linked lower AKG with reproductive aging and then tested supplementation in aging mice.

Human follicular fluid showed a tendency toward lower AKG with age. In mice, long-term AKG preserved ovarian function, oocyte quantity and quality and aspects of telomere maintenance.

The human component is observational. The intervention evidence is in mice, so the paper does not demonstrate that Ca-AKG improves fertility or IVF outcomes in women.

Key findings

  • Follicular-fluid AKG tended to decline with age in the human observations.
  • Long-term AKG administration preserved ovarian function and oocyte quality in aging mice.
  • Mechanistic findings implicated ATP synthase, nutrient sensing and mTOR signaling.

What this study can and cannot tell us

  • Human evidence is observational rather than interventional.
  • The supplementation experiments were performed in mice, not women.
  • Reproductive outcomes cannot be extrapolated to pregnancy, IVF success or live-birth benefit in humans.

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