{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:41:39Z","timestamp":1788486099796,"version":"build-2803163510"},"reference-count":139,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R00 AG050777"],"award-info":[{"award-number":["R00 AG050777"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL148352"],"award-info":[{"award-number":["R01 HL148352"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality. In addition to waning reproductive function, the decline in estrogen secretion at menopause contributes to multisystem aging and the initiation of frailty. Both reproductive and hormonal ovarian function are limited by the primordial follicle pool, which is established in utero and declines irreversibly until menopause. Because ovarian function is dependent on the primordial follicle pool, an understanding of the mechanisms that regulate follicular growth and maintenance of the primordial follicle pool is critical for the development of interventions to prolong the reproductive life span. Multiple pathways related to aging and nutrient-sensing converge in the mammalian ovary to regulate quiescence or activation of primordial follicles. The PI3K\/PTEN\/AKT\/FOXO3 and associated TSC\/mTOR pathways are central to the regulation of the primordial follicle pool; however, aging-associated systems such as the insulin-like growth factor-1\/growth hormone pathway, and transsulfuration\/hydrogen sulfide pathways may also play a role. Additionally, sirtuins aid in maintaining developmental metabolic competence and chromosomal integrity of the oocyte. Here we review the pathways that regulate ovarian reserve and oocyte quality, and discuss geroscience interventions that leverage our understanding of these pathways to promote reproductive longevity.<\/jats:p>","DOI":"10.1093\/gerona\/glaa204","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T06:47:24Z","timestamp":1597733244000},"page":"1551-1560","source":"Crossref","is-referenced-by-count":63,"title":["Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9343-9789","authenticated-orcid":false,"given":"Natalia","family":"Llarena","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Ohio"},{"name":"Reproductive Endocrinology and Infertility, Cleveland Clinic Women\u2019s Health Institute, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Hine","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"2021081309131056300_CIT0001","first-page":"1","article-title":"Births: final data for 2018","volume":"68","author":"Martin","year":"2019","journal-title":"Natl Vital Stat Rep"},{"key":"2021081309131056300_CIT0002","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1056\/NEJMoa0803072","article-title":"Cumulative live-birth rates after in vitro fertilization","volume":"360","author":"Malizia","year":"2009","journal-title":"N Engl J Med"},{"key":"2021081309131056300_CIT0003","author":"Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Reproductive Health"},{"key":"2021081309131056300_CIT0004","author":"Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Reproductive Health. 2017 Assisted Reproductive Technology Fertility Clinic Success Rates Report. 2018."},{"key":"2021081309131056300_CIT0005","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/01.gme.0000218683.97338.ea","article-title":"Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis","volume":"13","author":"Atsma","year":"2006","journal-title":"Menopause"},{"key":"2021081309131056300_CIT0006","doi-asserted-by":"crossref","DOI":"10.1016\/S0029-7844(97)00583-8","article-title":"Bone loss in young women with karyotypically normal spontaneous premature ovarian failure","author":"Anasti","year":"1998","journal-title":"Obstet 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