Oocytes in the mammalian ovary maintain extreme protein longevity to ensure the stability of the female germline over a woman's reproductive life. This study reveals that oocytes and ovarian proteostasis involve exceptionally long-lived proteins, which are essential for maintaining cellular functions such as mitochondrial activity, chromatin structure, and proteostasis. These proteins are not only present in oocytes but also in long-lived ovarian somatic cells. The data suggest that mammals enhance proteostasis through chaperones and antioxidants to maintain the female germline. However, protein longevity cannot fully prevent female germline senescence. Large-scale proteome profiling of ~8,890 proteins showed a decline in many long-lived proteins of the proteostasis network in aging ovaries, leading to female fertility decline. The female ovary stores primordial follicles containing oocytes and their associated somatic cells, which are not replenished after birth. The proteome of oocytes must be maintained in a healthy state throughout a woman's reproductive life to ensure the success of the next generation. The study used quantitative mass spectrometry, pulse-chase labelling, single-cell RNA-seq, and nanoscale secondary ion MS to analyze proteostasis in mammalian oocytes and ovaries. The results show that oocytes contain many extremely long-lived proteins, with mitochondrial proteins and proteostasis-promoting proteins being prominently enriched. The extreme longevity of ovarian proteins is supported by the high fraction of extremely long-lived proteins in the ovary compared to other post-mitotic tissues. The study also identified long-lived somatic cell types in the ovary, including granulosa, stromal, and theca cells. Proteostasis is maintained in aged oocytes, as protein aggregation does not increase with age and proteasome activity does not decay. However, the decline in long-lived proteins contributes to ovarian aging. The findings suggest that ovarian aging is associated with extensive changes in the ovarian proteome and a decrease of important long-lived proteins. The study highlights the importance of protein longevity in maintaining the female germline and the need for further research into the molecular mechanisms underlying ovarian aging.Oocytes in the mammalian ovary maintain extreme protein longevity to ensure the stability of the female germline over a woman's reproductive life. This study reveals that oocytes and ovarian proteostasis involve exceptionally long-lived proteins, which are essential for maintaining cellular functions such as mitochondrial activity, chromatin structure, and proteostasis. These proteins are not only present in oocytes but also in long-lived ovarian somatic cells. The data suggest that mammals enhance proteostasis through chaperones and antioxidants to maintain the female germline. However, protein longevity cannot fully prevent female germline senescence. Large-scale proteome profiling of ~8,890 proteins showed a decline in many long-lived proteins of the proteostasis network in aging ovaries, leading to female fertility decline. The female ovary stores primordial follicles containing oocytes and their associated somatic cells, which are not replenished after birth. The proteome of oocytes must be maintained in a healthy state throughout a woman's reproductive life to ensure the success of the next generation. The study used quantitative mass spectrometry, pulse-chase labelling, single-cell RNA-seq, and nanoscale secondary ion MS to analyze proteostasis in mammalian oocytes and ovaries. The results show that oocytes contain many extremely long-lived proteins, with mitochondrial proteins and proteostasis-promoting proteins being prominently enriched. The extreme longevity of ovarian proteins is supported by the high fraction of extremely long-lived proteins in the ovary compared to other post-mitotic tissues. The study also identified long-lived somatic cell types in the ovary, including granulosa, stromal, and theca cells. Proteostasis is maintained in aged oocytes, as protein aggregation does not increase with age and proteasome activity does not decay. However, the decline in long-lived proteins contributes to ovarian aging. The findings suggest that ovarian aging is associated with extensive changes in the ovarian proteome and a decrease of important long-lived proteins. The study highlights the importance of protein longevity in maintaining the female germline and the need for further research into the molecular mechanisms underlying ovarian aging.