Spermidine, an anti-aging supplement, improves fertility in mice

Women’s fertility plummets after age 35. Below that age, around 90% of those who want to get pregnant succeed, but the figure drops to 13% at age 45. The delay in the age at which women become mothers, added to the continuous decline in sperm quality, makes the need for medical assistance for getting pregnant increasingly common.

The success rate of those procedures also depends on age, especially due to the deterioration of ovarian reserve and the quality of the oocytes. This week, a team of researchers from the Nanjing Agricultural University published a study in the journal Nature Aging in which they found that spermidine improved the quality of eggs and fertility in mice of advanced age. The authors, led by Bo Xiong, believe this is a first step toward using spermidine as a treatment to improve fertility in older women.

Although spermidine has been shown to be a promising molecule to slow down or reverse some effects of aging, the road will still be long to translate the results as a treatment for infertility to humans. As Xiong explains by email, in their study they also documented “that the effects of spermidine on the quality of oocytes matured in vitro were preserved in pigs,” increasing “the confidence to perform the test in humans.” Their next step, as Xiong explains, “is a collaboration with a reproductive medicine center to test the effects of spermidine on human oocytes and their fertility.”

One of the important factors in human studies will be finding the right dose for treatment and its duration, because Xiong and his colleagues saw that too much of the molecule worsens the quality of oocytes in mice. “We will begin by testing the effects of spermidine on the maturation of human oocytes in vitro,” the researcher said.

Anti-aging molecule

Spermidine is a molecule that was first isolated in semen, but is found in most cells of all types of organisms, as well as in the ovaries. It participates in many important processes. At low levels it maintains cell stability, but when abundant, it destroys cells. Experiments with yeast, worms and flies have shown that, used as a supplement, it can prolong the life of these organisms, and in human cells it has been seen to promote autophagy, a cellular cleaning process that is also associated with the benefits of fasting. This potential of spermidine supplementation is being tested in human trials to treat high blood pressure, depression and aging of the immune system.

The authors of the work explain that “although a growing number of studies have reported the restorative effect of spermidine on the aging of somatic cells, its effect on the aging of oocytes has not been clarified.” To do so, they compared the metabolite profile of young mice, about 7 weeks old, with that of others that would be equivalent to middle age in humans, about one year old (54 weeks). Along with other changes between the ovaries of young and old females, they saw that the amount of spermidine decreased with age.

In a second part of the experiment, they gave spermidine to older females, putting it in the water and injecting it. The researchers saw that it improved the quantity and quality of their follicles, the structures from which eggs are formed. Furthermore, in what University of Graz researchers Andreas Zimmermann and Frank Madeo, in another article published in Nature Aging, consider “the most captivating finding of the study,” “supplementing the aging females with spermidine almost doubled the size of their litters.”

Since the aging of the ovaries is connected to the general aging of the organism, the authors of the study wanted to examine if what was seen when spermidine was given to mice was replicated in oocytes studied in vitro. They found that signs of aging were also reversed in vitro, and they identified two main mechanisms that explain it: autophagy and mitophagy, a cleaning process similar to the previous one that occurs in the mitochondria, organelles that produce most of the energy of the body’s cells. Spermidine is thus confirmed to be the basis of potential medications that can combat effects of aging.

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