Longevity Briefs: Why Do Ovaries Age So Quickly?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem: Functionally speaking, the ovaries are the fastest-ageing human organ, as they stop fulfilling their main function decades before any other organ system will usually start to fail. Humans are an extreme outlier in this regard, as females of most other species do not undergo the menopause and remain fertile for most of their lives. In humans, ageing ovaries suffer from diminished ovarian reserves (DOR) – a decrease in the number and quality of egg cells. In this study, researchers set out to investigate this phenomenon and why it happens.

The discovery: Researchers studied granulosa cells from women with DOR. These are cells within the ovaries that produce hormones to support the development of egg cells. The researchers found that in women with DOR, these granulosa cells had signs of increased autophagy. Autophagy, which literally means ‘self-eating’, is a process in which cells destroy and recycle their own worn out components. Autophagy is generally a good thing and tends to diminish with age, but in another example of biology being less straightforward than we might like, it seems that too much autophagy can be a bad thing in granulosa cells, leading to their death.

The researchers found that the levels of an oestrogen receptor on the granulosa cells – oestrogen receptor beta (ERβ) – was linked to the level of autophagy, and that autophagy could be reduced in cultured granulosa cells by genetically removing ERβ. This seemed to improve the function of the granulosa cells, but this improvement was reversed by drugs that boosted autophagy. The researchers then moved to mouse models of DOR and gave them ERβ blocking molecules. The mice that received treatment appeared to have improved ovarian function, producing more mature egg cells, and were also more fertile, with bigger litters when compared to the untreated controls.

The implications: This is an intriguing study showing a mechanism that could potentially be targeted to prevent or reverse ovarian ageing. However, since ovarian ageing in humans is so unusual is so specific to our species and cannot really be replicated in animals, we can’t conclude too much from mouse studies. If the importance of this mechanism is confirmed in humans, it could be quite an important advance in the field of reproductive ageing. On the other hand, high levels of autophagy could be playing some beneficial role, such as suppressing granulosa cell tumours, a rare type of ovarian cancer. More autophagy is generally considered to be beneficial when it comes to most age-related diseases, but ageing is complicated and made up of many different process. In a manner reminiscent of telomere shortening, which helps prevent cancer in early life but contributes to ageing and cancer in late life, autophagy might be suppressing some aspects of ageing at the cost of faster loss of reproductive function.