Can Reprogramming Factors Rejuvenate the Ovary? – Carlos Simon Foundation

Carlos Simon Foundation for Research in Women’s Health shared a post on LinkedIn:

“At the Carlos Simon Foundation, our research explores how partial cellular reprogramming could help restore ovarian function and improve fertility outcomes.

By applying the Yamanaka factors in a controlled way, we aim to rejuvenate ovarian cells without altering their identity, offering a potential path to extend reproductive lifespan safely.

This new article from Inside Women’s Health explains the science behind ovarian rejuvenation and the progress of the CAROLINA Project, our ongoing study in collaboration with INCLIVA.

Why do ovaries age faster than other organs?

Aging is a natural process, but the ovaries are unique in how early they decline compared to other organs. While the heart or liver may function well into old age, ovarian function starts to fall after the mid-30s. This decline affects both the number and the quality of eggs, making conception more difficult and increasing the risk of chromosomal abnormalities in embryos. For women who postpone motherhood, this biological reality can turn into a significant challenge. Until recently, ovarian aging was considered inevitable and irreversible.

What are Yamanaka factors, and why do they matter?

In 2006, Dr. Shinya Yamanaka identified four genes—Oct4, Sox2, Klf4, and c-Myc—that can ‘reset’ a cell’s identity. By activating these genes, specialized adult cells can be reprogrammed into pluripotent stem cells, capable of becoming any tissue in the body. This discovery won the Nobel Prize and changed our understanding of biology. It was like finding a hidden reset button for cellular life. In the context of ovarian aging, these factors raise a fascinating question: could we use them not to erase identity, but to rejuvenate cells while keeping their function?

Partial reprogramming: rejuvenation without erasing identity

Reprogramming cells all the way back to a stem cell state is powerful, but risky. It removes the cell’s identity, and if applied unchecked, it could lead to uncontrolled growth or tumor formation. Scientists have found a safer approach: partial reprogramming. In this strategy, Yamanaka factors are applied only for short, controlled periods. Instead of turning back into stem cells, the ovarian cells undergo a ‘soft reset.’ This restores youthful epigenetic marks, repairs DNA stability, reduces inflammation, and removes signs of cellular aging, while allowing the cells to remain ovarian cells. In other words, the identity stays the same, but the age is turned back.

What does this mean for fertility?

If successful, partial reprogramming could improve the quality of oocytes and the environment in which they mature. Imagine a woman in her forties whose eggs could regain some of the characteristics of her thirties. This could increase the chances of conception, reduce the need for egg donation, and potentially expand the reproductive window. Beyond fertility, it could also delay the onset of menopause and its associated health effects, such as osteoporosis and cardiovascular risk.

The CAROLINA Project: from concept to application

At the Carlos Simon Foundation, the CAROLINA Project is investigating whether partial reprogramming can safely rejuvenate ovaries. Our approach focuses on delivering Yamanaka factors directly to the ovary through perfusion, a technique that allows precise exposure while minimizing risks. By combining single-cell sequencing, epigenetic profiling, and ex vivo ovarian perfusion, the project aims to map how ovarian cells respond to reprogramming and define safe protocols for future therapies. While this research is still in the experimental phase, its implications are transformative: from improving fertility treatments to offering women more control over their reproductive lifespan.”

Other posts featuring Carlos Simon Foundation for Research in Women’s Health on Fertility News.