'Protein factories' linked to age-related infertility

Researchers at Nankai University in Tianjin have identified a breakthrough biological target for treating age-related infertility.

The study, published in Cell Reports Medicine, offers a fresh perspective on why fertility often sharpens its decline after the age of 35 and suggests that a well-known longevity drug might be the key to reversing it.

The research team, led by professor Liu Lin, found that after age 34, a woman's oocytes (egg cells) and their supporting cumulus cells begin to exhibit excessive activity in their ribosomes — the structures responsible for protein synthesis.

This "ribosomal hyperactivity", the researchers said, disrupts normal cell function and contributes to infertility.

Ribosomes are often termed the "protein synthesis factories" within human cells.

The study revealed that overactive ribosomes increase protein production but reduce protein stability, which may accelerate ovarian aging and degrade embryonic quality.

Research team member Li Jie said their study indicates that abnormal ribosomal function is a significant underlying factor in female infertility, which has been largely overlooked in previous research.

"Excess ribosomal activity leads to a decline in egg quality, and this effect is not limited to oocytes themselves," Li said. "With aging, surrounding cumulus cells undergo similar changes, collectively impairing the development potential of eggs and embryos, and sometimes resulting in infertility."

Based on these insights, the team further experimented with the antibiotic rapamycin. Originally an antifungal drug, rapamycin gained attention in 2022 when Harvard Medical School researchers confirmed it extended the life span in mice, supporting its potential as an anti-aging agent.

In this study, researchers extracted oocytes and cumulus cells from female mice. Professor Liu said, "It showed rapamycin effectively stabilizes cellular proteins, improving ovarian environments and enhancing embryo quality."

The research findings have been further verified in clinical applications. Liu's team collaborated with institutions such as the Children's Hospital of Shanxi Province, the Sixth Medical Center of PLA General Hospital, and Tianjin Medical University General Hospital.

In their first stage clinical trial, over 100 women who had previously failed in vitro fertilization were included and divided into two groups, an experimental group and a control group.

"Our clinical trials primarily targeted patients whose poor egg or embryo development was age-related. Results showed that rapamycin intervention increased the pregnancy rate by approximately 20 percent, while significantly improving the number of highquality embryos," Liu said.

These results confirmed that short-term administration of rapamycin offers a potential avenue for women who had previously failed IVF or experienced embryo development arrest to achieve successful pregnancies and possibly deliver healthy babies.

Low-dose orally taken rapamycin shows promise for infertility intervention, with current data indicating good safety and no adverse effects on embryonic viability, Liu said.

Wu Xueqing, a doctor from the Children's Hospital of Shanxi Province, said the outcome is inspiring and opens a new pathway for understanding and treating age-related infertility.

However, the potential side effects of rapamycin should not be overlooked. According to The Economist, Bryan Johnson, a California-based tech entrepreneur who had long pursued "the quest for immortality" as a personal mission, reportedly used rapamycin for anti-aging purposes but ceased its use last year due to significant side effects. These included abnormal cholesterol and blood sugar levels, increased heart rate and heightened risk of skin infections.

"Future efforts should focus on larger-scale clinical trials to further validate rapamycin's efficacy in treating female infertility. Optimized complementary treatment protocols are also essential moving forward," Wu said.

Zang Yifan contributed to this story.

yandongjie@chinadaily.com.cn