The study investigates the maintenance of oocytes and ovarian proteostasis in mammals, focusing on the extreme protein longevity observed in these tissues. Oocytes contain a significant number of long-lived proteins, which persist from birth and contribute to the longevity of the female germline. These proteins are involved in various cellular functions, including mitochondria, cytoskeleton, chromatin, and proteostasis. The study uses a combination of techniques, including quantitative mass spectrometry, pulse-chase labeling, single-cell RNA-seq, and NanoSIMS, to analyze protein turnover and distribution in oocytes and ovaries. Key findings include: 1. **Extreme Protein Longevity**: Mouse ovaries have a higher fraction of extremely long-lived proteins compared to other post-mitotic tissues. These proteins have half-lives well above those in other organs, with many persisting throughout the mouse's lifespan. 2. **Proteostasis Maintenance**: Despite the long-lived proteins, protein aggregation in oocytes does not increase with age, and proteasomal activity does not decay. This suggests that the extreme protein longevity helps maintain proteostasis and cellular function. 3. **Aging and Protein Loss**: While extreme protein longevity helps preserve the germline, it cannot fully prevent the age-related decline in fertility. The study identifies specific proteins and pathways that decrease with aging, contributing to ovarian aging and fertility decline. 4. **Long-lived Somatic Cells**: The study also reveals that subsets of ovarian somatic cells, such as granulosa, thecal, and stromal cells, are highly enriched in long-lived proteins, indicating that the aging of these cells also contributes to ovarian aging. Overall, the research highlights the importance of extreme protein longevity in maintaining the female germline and the complex interplay between oocyte and somatic cell aging in the ovary.The study investigates the maintenance of oocytes and ovarian proteostasis in mammals, focusing on the extreme protein longevity observed in these tissues. Oocytes contain a significant number of long-lived proteins, which persist from birth and contribute to the longevity of the female germline. These proteins are involved in various cellular functions, including mitochondria, cytoskeleton, chromatin, and proteostasis. The study uses a combination of techniques, including quantitative mass spectrometry, pulse-chase labeling, single-cell RNA-seq, and NanoSIMS, to analyze protein turnover and distribution in oocytes and ovaries. Key findings include: 1. **Extreme Protein Longevity**: Mouse ovaries have a higher fraction of extremely long-lived proteins compared to other post-mitotic tissues. These proteins have half-lives well above those in other organs, with many persisting throughout the mouse's lifespan. 2. **Proteostasis Maintenance**: Despite the long-lived proteins, protein aggregation in oocytes does not increase with age, and proteasomal activity does not decay. This suggests that the extreme protein longevity helps maintain proteostasis and cellular function. 3. **Aging and Protein Loss**: While extreme protein longevity helps preserve the germline, it cannot fully prevent the age-related decline in fertility. The study identifies specific proteins and pathways that decrease with aging, contributing to ovarian aging and fertility decline. 4. **Long-lived Somatic Cells**: The study also reveals that subsets of ovarian somatic cells, such as granulosa, thecal, and stromal cells, are highly enriched in long-lived proteins, indicating that the aging of these cells also contributes to ovarian aging. Overall, the research highlights the importance of extreme protein longevity in maintaining the female germline and the complex interplay between oocyte and somatic cell aging in the ovary.