Ovarian derived exosomal miRNA as a juvenile protective factors

卵巢来源的外泌体 miRNA 作为青少年保护因子

• 批准号: 10674254
• 负责人: MICHAL Mateusz MASTERNAK
• 金额: $ 28.66万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10674254
• 关键词: Adolescent; Aging; Animals; Blood; Blood Circulation; Cell Compartmentation; Cells; Data; Development; Diabetes Mellitus; Disease; Distant; Dwarfism; Elderly; Estradiol; Female; Genes; Genetic; Genome Stability; Goals; Gonadal Steroid Hormones; Gonadal structure; Health; Health Benefit; Hormonal; Hormones; Human; Hypersensitivity; Incidence; Inflammation; Insulin; Insulin Resistance; Life; Life Style; Link; Longevity; Membrane Lipids; Menopause; Metabolic syndrome; MicroRNAs; Molecular; Molecular Profiling; Mus; Organ; Ovarian; Ovarian Tissue; Ovarian aging; Ovary; PIK3CG gene; Pattern; Periodicity; Persons; Play; Population; Premenopause; Process; Production; Proto-Oncogene Proteins c-akt; Race; Regulation; Research; Role; Serum; Signal Pathway; Somatic Cell; Source; Steroids; Testing; Therapeutic; Tissues; Transplant Recipients; Transplantation; Vesicle; Weight Gain; age related; anti aging; base; circulating microRNA; dietary; differential expression; disorder risk; exosome; fetal; healthspan; improved; in vivo; inhibitor; insulin regulation; insulin sensitivity; insulin signaling; male; novel; ovarian reserve; ovary transplantation; prepuberty; preservation; protective factors; reproductive; reproductive function; reproductive longevity; reproductive organ; restoration; transcriptome

The long-term goal of our research is to identify the role of young ovaries in production of therapeutic juvenile protective factors in form of exosomes carrying putative pro-longevity microRNAs (miRNAs). With the growing population of elderly people, there is a growing incidence of age-related diseases including metabolic syndrome, insulin resistance and diabetes mellitus. There is a well-established link between health and the function of reproductive organs and longevity. Importantly, it was shown that transplanting young ovaries into old mice delays aging and increases lifespan by over 40%. Unfortunately, the detailed mechanism by which young ovaries provide these longevity benefits is still undetermined. One of the possible benefits could be linked to an enhanced production of sex hormones, yet it was also shown that eliminating sex hormone producing cells in ovaries before transplantation, still produced pro-longevity benefits. Importantly, for the purpose of this proposal our novel findings suggest that ovaries express and secrete a variety of different exosomes containing miRNAs that might play an important role in the stability of transcriptome in gonads and diversity of different distant organs. Based on our findings we propose the general hypothesis is that young ovaries increase healthspan and longevity by secreting exosomes enriched with miR-181b-5p and miR-1249-3p, which target genes involved in insulin signaling. In the proposed studies we will investigate the effects of ovaries from young or long-living animals on the production and secretion of putative pro-longevity miRNA and the mechanism by which these miRNAs modulate high insulin sensitivity during aging. To test our hypothesis we propose three specific aims: Specific Aim 1: Determine if ovaries serve as a source of circulating factors that improve healthspan. Specific Aim 2: Assess the influence of ovarian-derived miRNAs on insulin sensitivity Specific Aim 3: Determine the ovarian secretory pattern of circulating exosomal miRNAs in mice and human ovaries.

我们研究的长期目标是确定年轻卵巢在治疗性幼体生产中的作用 外泌体形式的保护因子携带假定的长寿 microRNA (miRNA)。随着 随着老年人口的不断增加，代谢性疾病等与年龄相关的疾病发病率也随之增加 综合征、胰岛素抵抗和糖尿病。健康与健康之间存在着明确的联系 生殖器官的功能和长寿。重要的是，研究表明，将年轻的卵巢移植到 老年小鼠延缓衰老，寿命延长40%以上。不幸的是，详细的机制 年轻的卵巢是否能提供这些长寿益处尚未确定。可能的好处之一可能是 与性激素产生的增加有关，但也有研究表明，消除性激素 在移植前在卵巢中产生细胞，仍能产生延长寿命的益处。重要的是，对于 该提议的目的我们的新颖发现表明卵巢表达和分泌多种不同的 含有 miRNA 的外泌体可能在性腺转录组的稳定性中发挥重要作用 不同远端器官的多样性。根据我们的发现，我们提出一般假设：年轻人 卵巢通过分泌富含 miR-181b-5p 和 miR-1249-3p 的外泌体来延长健康寿命和寿命， 其目标基因涉及胰岛素信号传导。在拟议的研究中，我们将调查以下因素的影响： 年轻或长寿动物的卵巢对假定的长寿 miRNA 的产生和分泌的影响 以及这些 miRNA 在衰老过程中调节高胰岛素敏感性的机制。来测试我们的 假设我们提出三个具体目标： 具体目标 1：确定卵巢是否是改善健康寿命的循环因子的来源。具体的 目标 2：评估卵巢来源的 miRNA 对胰岛素敏感性的影响 具体目标 3：确定 小鼠和人类卵巢中循环外泌体 miRNA 的卵巢分泌模式。

项目成果

Senolytic treatment fails to improve ovarian reserve or fertility in female mice.

Senolytic 治疗无法改善雌性小鼠的卵巢储备或生育能力。

• 发表时间: 2024-06
• 影响因子: 5.6
• 作者: Garcia, Driele N;Hense, Jessica D;Zanini, Bianka M;Isola, Jose V V;Prosczek, Juliane B;Ashiqueali, Sarah;Oliveira, Thais L;Mason, Jeffrey B;Schadock, Ines C;Barros, Carlos C;Stout, Michael B;Masternak, Michal M;Schneider, Augusto
• 通讯作者: Schneider, Augusto

Effects of calorie, protein, and branched chain amino acid restriction on ovarian aging in mice.

热量、蛋白质和支链氨基酸限制对小鼠卵巢衰老的影响。

• DOI: 10.1016/j.repbio.2024.100856
• 发表时间: 2024-01-30
• 期刊: Reproductive biology
• 影响因子: 2.1
• 作者: G. B. Veiga;B. Zanini;D. N. Garcia;Jéssica D Hense;M. M. Barreto;J. Isola;R. Mondadori;M. Masternak;Michael B Stout;Augusto Schneider
• 通讯作者: Augusto Schneider

Ovarian aging in humans: potential strategies for extending reproductive lifespan.

人类卵巢衰老：延长生殖寿命的潜在策略。

• 发表时间: 2023-08
• 影响因子: 5.6
• 作者: Cavalcante, Marcelo Borges;Sampaio, Olga Goiana Martins;Câmara, Fernanda Eunice Araújo;Schneider, Augusto;de Ávila, Bianca Machado;Prosczek, Juliane;Masternak, Michal M;Campos, Adriana Rolim
• 通讯作者: Campos, Adriana Rolim

Fisetin modulates the gut microbiota alongside biomarkers of senescence and inflammation in a DSS-induced murine model of colitis.

在 DSS 诱导的小鼠结肠炎模型中，非瑟酮与衰老和炎症的生物标志物一起调节肠道微生物群。

• 发表时间: 2024-06
• 影响因子: 5.6
• 作者: Ashiqueali, Sarah A;Chaudhari, Diptaraj;Zhu, Xiang;Noureddine, Sarah;Siddiqi, Sarah;Garcia, Driele N;Gostynska, Aleksandra;Stawny, Maciej;Rubis, Blazej;Zanini, Bianka M;Mansoor, Mishfak A M;Schneider, Augusto;Naser, Saleh A;Yadav, Hariom;Mas
• 通讯作者: Mas