College of Veterinary Medicine, Department of Veterinary Clinical and Life Sciences, Center for Integrated BioSystems, Utah State University, Logan, UT, 84322, USA.
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Geroscience. 2024 Feb;46(1):1159-1173. doi: 10.1007/s11357-023-00865-8. Epub 2023 Jul 15.
Effort toward reproduction is often thought to negatively influence health and survival. Reproduction has been shown to influence metabolism, but the pathways and mechanisms have yet to be thoroughly elucidated. In the current experiments, our aim was to dissect the role of young and old ovarian tissues in the response to oxidative stress, through changes in liver oxidative stress response proteins. Liver proteins were analyzed in control mice at 4, 13, and 27 months of age and compared to 23-month-old mice which received young ovarian tissue transplants (intact or follicle-depleted) at 13 months of age. In control mice, of the 29 oxidative stress response proteins measured, 31% of the proteins decreased, 52% increased, and 17% were unchanged from 13 to 27 months. The greatest changes were seen during the period of reproductive failure, from 4 to 13 months of age. In transplanted mice, far more proteins were decreased from 13 to 23 months (93% in follicle-containing young ovary recipients; 62% in follicle-depleted young ovary recipients). Neither transplant group reflected changes seen in control mice between 13 and 27 months. Estradiol levels in transplant recipient mice were not increased compared with age-matched control mice. The current results suggest the presence of a germ cell- and estradiol-independent ovarian influence on aging-associated changes in the response to oxidative stress, which is manifest differently in reproductive-aged adults and post-reproductive-aged mice. The results presented here separate chronological and ovarian aging and the influence of estradiol in the response to aging-associated oxidative stress and support a novel, estradiol-independent role for the ovary in female health and survival.
人们通常认为生殖努力会对健康和生存产生负面影响。已经表明生殖会影响新陈代谢，但途径和机制尚未得到彻底阐明。在当前的实验中，我们的目的是通过改变肝脏氧化应激反应蛋白来剖析年轻和老年卵巢组织在应对氧化应激中的作用。在 4、13 和 27 个月龄的对照小鼠中分析了肝脏蛋白，并与 13 个月龄时接受年轻卵巢组织移植（完整或卵泡耗竭）的 23 个月龄小鼠进行了比较。在对照小鼠中，在所测量的 29 种氧化应激反应蛋白中，有 31%的蛋白减少，52%的蛋白增加，17%的蛋白从 13 个月到 27 个月保持不变。最大的变化发生在生殖失败期间，即从 4 个月到 13 个月。在移植小鼠中，从 13 个月到 23 个月，更多的蛋白减少（含卵泡的年轻卵巢受体减少 93%；卵泡耗竭的年轻卵巢受体减少 62%）。两个移植组都没有反映出对照小鼠在 13 至 27 个月之间的变化。与年龄匹配的对照小鼠相比，移植受体小鼠的雌二醇水平没有增加。目前的结果表明，生殖细胞和雌二醇独立的卵巢对与衰老相关的氧化应激反应变化有影响，这种影响在生殖期成年和生殖后成年小鼠中表现不同。这里呈现的结果将年龄和卵巢衰老以及雌二醇对衰老相关氧化应激的影响分开，并支持卵巢在女性健康和生存中具有独立于雌二醇的新作用。
