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expert reaction to study looking at spermidine supplementation and age-related fertility decline in mice

A study published in Nature Aging looks at the use of spermidine to enhance fertility in mice. 


Prof Ying Cheong, Professor of Reproductive Medicine, University of Southampton, said:

“Spermadine, a protein metabolite, is increasingly recognised as an anti-ageing therapy.  Zhang and colleagues shown in their elegant experiments that supplementation of spermidine helps improve egg quality in mice by enhancing how cells use energy and regulate cell death.

“It is premature to advise women to take spermidine as a supplement because there are unanswered questions around preparation, dosage, length of use, side effects and clinical benefit.”


Comment gathered by our friends at the German SMC:

PD Dr Verena Nordhoff, Head of the Reproductive Medicine Laboratory at the Centre for Reproductive Medicine and Andrology, Münster University Hospital:

“Spermidine and other similar compounds – called polyamines – have been discussed in connection with ageing processes for many years. The production of polyamines decreases with age, therefore these molecules have been investigated as possible anti-ageing compounds in various studies.

“The authors of the present study have found that the production of spermidine also decreases in the mouse ovary during the ageing process. Therefore, they investigated whether exogenous administration of this substance could mitigate the effects of ageing on female mouse fertility. They found that both injections and supplementation of the drinking water improved the fertility of female aged mice. The addition of spermidine during in vitro culture of immature eggs from aged mice or pigs helped more eggs to mature (to the metaphase II stage) and also improved their overall quality.

“Overall, this is a very good and solid study. However, we must keep in mind that mice are very different from humans, especially in terms of the ageing process. A female mouse lives for about two years and is fertile for most of her life. In contrast, humans are long-lived and the decline in female fertility with age is associated with other complications, which are absent or maybe irrelevant in mice.”


Transferability to humans

“Whether the findings obtained from the mouse model are transferable to humans is an important question. Fertility and ovarian function are quite different in mice and humans. Laboratory mice are inbred animals and thus genetically very similar, live only about two years, and have no menopause. In contrast, humans are genetically very diverse and the female reproductive lifespan lasts several decades, although the decline in fertility can be highly individual. The fact that the authors were also able to demonstrate positive effects in pig eggs is reassuring, but this approach is still very far from being routinely used in humans.

“It is difficult to say whether spermidine should be prescribed as a supplement to women who are experiencing fertility problems. Neither the required dose nor the treatment duration necessary to achieve an effect on the ovaries in humans have been established. In addition, spermidine showed epigenetic effects in animal studies; whether or how this could possibly affect offspring is unknown. Therefore, further studies would first need to be conducted to ensure the short- and long-term safety of spermidine and similar compounds before human trials could be initiated.”


‘Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging’ by Yu Zhang et al. was published in Nature Aging at 16:00 UK time on Monday 16 October 2023.

DOI: 10.1038/s43587-023-00498-8


Declared interests

Prof Ying Cheong: “Medical Director of Complete Fertility.”

For all other experts, no reply to our request for DOIs was received.


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