[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-455453-105":59,"doc-detail-455453-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","ovarian-aging-a-multifaceted-perspective-on-mechanisms-letter-to-the-editor","Ovarian Aging: A Multifaceted Perspective on Mechanisms - LETTER TO THE EDITOR","","Ovarian aging is presented as an inevitable, age-linked biological process that drives functional decline across reproductive and systemic organs. The letter highlights evidence that ovarian vascular endothelial aging can precede nonreproductive organ changes, positioning ovarian aging as a key indicator of female bodily aging. Mechanistic focus includes mitochondrial dysfunction via oxidative mitochondrial DNA damage and NAD+/SIRT2–related disruptions, alongside genetic DNA damage response alterations and apoptosis pathways, and epigenetic/posttranslational regulation impacts on oocyte quality and fertility outcomes.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ovarian-aging-a-multifaceted-perspective-on-mechanisms-letter-to-the-editor/455453/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ovarian-aging-a-multifaceted-perspective-on-mechanisms-letter-to-the-editor/455453.png","ImageObject",300,407,{"name":92,"@type":93},"Himbo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is ovarian aging considered a primary marker of female bodily aging?","Question",{"text":113,"@type":114},"Ovarian aging is described as initiating age-related decline across multiple systems and organs, and as a key indicator influencing the aging of multiple organs.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does mitochondrial dysfunction contribute to ovarian aging?",{"text":118,"@type":114},"Mitochondrial DNA damage from oxidative stress reduces mitochondrial DNA copy number and function, disrupts mitochondrial energy homeostasis, and promotes accumulation of mitoROS that worsens oocyte quality decline.",{"name":120,"@type":111,"acceptedAnswer":121},"What role do genetic mechanisms play in the decline of ovarian reserve?",{"text":122,"@type":114},"Abnormalities in DNA damage repair genes and age-related declines in key repair factors reduce genomic stability, activate p53-p21 signaling, and promote apoptosis of granulosa cells and follicular atresia.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},455453,1791069026,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},687197100911,"https://ap-avatar.wpscdn.com/avatar/a000239b6f1da00475?x-image-process=image/resize,m_fixed,w_180,h_180&k=1785132997149421697","Cell Proliferation   \n LETTER TO THE EDITOR  OPEN ACCESS   \nOvarian Aging: A Multifaceted Perspective on Mechanisms  \nXiaoqing Zhang1  | Xinyi Dong1 | Xue Zhang1 | Suying Yuan1 | Qiran Zhang1 | Zilu Guo1 | Xiaoxue Yang1 | Qionghua Wang2 | Tianlan Yang2 | Donghui Huang1,3   \n1Institute of Reproduction Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China | 2Maternal and Child Health Centre of Linxiang District of Lincang City, Lincang, China | 3Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, China  \nCorrespondence: Donghui Huang ([jhsyyjs@126.com](jhsyyjs@126.com))  \nReceived: 5 March 2025 | Revised: 30 September 2025 | Accepted: 24 October 2025  \nFunding: This work was supported by the Independent Innovation Fund of HUST (5003519022) and the Education and Industry Collaboration in Joint Training Program (220601164154747, 220601164013611) .  \nTo the editor,  \nAging is a spontaneous and inevitable process in biological organisms over time. Recent research in the field of cell biology suggests a novel perspective on the role of the vascular system in the aging process [1] . Mu L. found that the aging process of ovarian vascular endothelium precedes that of nonreproductive organ vascular endothelium [2] . This phenomenon contributes to the ovarian tissue's position as the primary human tissue to manifest substantial age-related functional deterioration [2] . Ovarian aging has been demonstrated to directly initiate the aging process in multiple systems and organs throughout the body [2] . Conversely, research findings suggest that for every 1-year delay in menopausal age, there is a 2% decrease in all-cause mortality [3]. Consequently, ovarian aging is regarded as the primary indicator of female bodily aging, influencing the aging of multiple organs.  \nOvarian aging is a complex biological process closely linked to human reproductive capacity and population size. It is characterised by the gradual decline of ovarian function with advancing age, accompanied by follicular depletion, diminished egg quality and changes in menstrual cycles, ultimately leading to loss of fertility and menopause [2] . Traditional research has focused on follicular depletion and endocrine changes, while recent evidence reveals complex interactions among mitochondrial dysfunction, epigenetic alterations, metabolic disordersand immune microenvironment remodeling [4–8] . We propose that mitochondrial dysfunction, by affecting energy metabolism and oocyte quality, represents a core driver of ovarian aging. By reviewing the latest research advances in these mechanisms,  \nelucidating their interactions and identifying potential therapeutic targets, we aim to provide a scientific foundation for addressing ovarian aging.  \n1 | Mechanism  \n1.1 | Mitochondrial Dysfunction  \nExtensive research indicates that mitochondrial DNA damage plays a pivotal role in ovarian aging. Mitochondrial DNA is devoid of histone protection, and electron leakage in the mitochondrial respiratory chain renders it vulnerable to oxidative stress damage from reactive oxygen species (ROS) [6] . Chiang L. J. et al. discovered that oxidative mitochondrial damage results in a decrease in mitochondrial DNA copy number and function in the ovary [6] . This, in turn, induces ovarian aging and follicular atresia [6] . The relevant mechanism can be seen in Figure S1 . During the process of ovarian aging, a dysregulation of the NAD+/SIRT2 pathway has been observed to cause an imbalance in antioxidant pathways, resulting in a disruption of mitochondrial energy homeostasis [9] . As the ovary undergoes the process of aging, there is an increase in the expression of the NAD-degrading enzyme CD38 [9] . This increase in expression leads to a decrease in NAD+ levels anda weakening of SIRT2 deacetylase activity [9] . This results ina disruption of mitochondrial energy homeostasis, an inhibition of PINK1/Parkin-mediated mitochondrial auto","cbCaitxlZFQeHqxn","https://ap.wps.com/l/cbCaitxlZFQeHqxn","pdf",477316,"English","# Mechanism\n## Mitochondrial Dysfunction\n## Genetic Mechanisms\n## Epigenetic and Posttranslational Modifications (PTM)","[{\"question\":\"Why is ovarian aging considered a primary marker of female bodily aging?\",\"answer\":\"Ovarian aging is described as initiating age-related decline across multiple systems and organs, and as a key indicator influencing the aging of multiple organs.\"},{\"question\":\"How does mitochondrial dysfunction contribute to ovarian aging?\",\"answer\":\"Mitochondrial DNA damage from oxidative stress reduces mitochondrial DNA copy number and function, disrupts mitochondrial energy homeostasis, and promotes accumulation of mitoROS that worsens oocyte quality decline.\"},{\"question\":\"What role do genetic mechanisms play in the decline of ovarian reserve?\",\"answer\":\"Abnormalities in DNA damage repair genes and age-related declines in key repair factors reduce genomic stability, activate p53-p21 signaling, and promote apoptosis of granulosa cells and follicular atresia.\"}]","Ovarian Aging: A Multifaceted Perspective on Mechanisms - LETTER TO THE EDITOR | PDF",1790742991,13]