Breakthrough in Ovarian Aging: Study Shows Promising Results

Scientists have documented that resveratrol reverses several features of ovarian aging in mice while improving mitochondrial health and activating major sirtuins.

In most mammals, ovarian aging is accelerated compared to other organs and systems. While the reasons for this accelerated loss are not clear, some notable triggers include issues with ATP production, a decrease in mitochondrial activity, accumulation of DNA damage, and chromosomal abnormalities. 

One of the more famous molecules in longevity, resveratrol is a polyphenol found in peanuts, grapes, and red wine. Similar to other polyphenols, it contains anti-inflammatory properties and antioxidants. The molecule has been shown to stimulate the production of beneficial proteins in the sirtuin family, as well as enhance mitochondrial function. 

The positive effect of resveratrol supplementation on ovarian functioning in mice was already demonstrated in previous studies. However, the duration of treatment was extremely long, lasting about 6 to 12 months. Additionally, the 6-month treatment was observed to be ineffective because in most cases, it ended while the mice were still young to experience a marked decline in ovarian function. 

In the new study, researchers were looking to create a shorter protocol that would still relay these positive effects. The mice were therefore treated with resveratrol for periods of 1, 12, or 22 weeks until the age of 47 weeks—which translates to about 40 years in humans. Mice, like humans, also exhibit impaired ovarian function at this age. 

During the study, the researchers documented that the treatment did not alter the mice’s body weight—since such a change would have affected ovarian function and disrupted the results. The mice’s estrous cycles were also observed to be normal. 

In both the study and control groups, IVF was performed once the treatment was completed, with a number of tests run. The findings showed that the old untreated controls had fewer ovulated oocytes compared to the young mice. However, in all groups treated, this decline was reduced, even though it was not fully reversed. 

Notably, the most enhanced reversal took place in the group treated for 12 weeks, while the one-week treatment showed a slight improvement. On the other hand, fertilization rate only improved in the 22-week group—however, this was not considered to be a serious issue, since even in the old untreated mice, it didn’t drop below 60%

As for the implantation rate, it was higher than 80% in the young mice, but dropped below 20% in old untreated controls. However, it was reversed to youthful levels in every treatment group, including the one-week group. 

As for the offspring rate, it measured about 60% in the young mice, and dropped below 10% for the untreated old mice. As for the treated group, it was noticeably restored in all three treatment plans. However, it was most effective in the 22-week treatment group, and enhanced the live offspring rate back to youthful levels. Lastly, no abnormalities were detected in the offspring or placentas derived  from the mice after the 22-week treatment, indicating that the treatment was safe. 

Researchers also analyzed the serum levels of resveratrol in all study groups. They found that there was a strong correlation between resveratrol levels and implantation rate, and a borderline strong correlation between resveratrol levels and live offspring rate. 

There was an even stronger correlation between resveratrol serum levels and the expression of sirtuins SIRT2 and SIRT6. The study also showed that the resveratrol-treated mice displayed similar mitochondrial potential as the young controls. Resveratrol levels also significantly boosted ATP production, although not back to youthful levels. The researchers also documented that the treatment did not alter the mitochondrial DNA copy number, which means that the observed improvement in mitochondrial function was not a result of increasing the number of mitochondria, but an increase in mitochondrial health. 

In conclusion, the study confirms that a relatively short treatment of resveratrol started later in life can significantly reverse ovarian aging in mice. It is also beneficial to mitochondrial function and acts as a sirtuin activator.