[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-426691-105":59,"doc-detail-426691-en":134},{"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":127,"head_meta":129,"extra_data":131,"updated_unix":133},105,"en","more-than-a-loading-control-studying-the-actin-cytoskeleton-for-novel-anti-aging-mechanisms-part","MORE THAN A LOADING CONTROL - STUDYING THE ACTIN CYTOSKELETON FOR NOVEL ANTI-AGING MECHANISMS - Part","","Actin cytoskeleton integrity is essential for cell division, autophagy, chaperone activity, and vesicle trafficking, yet aging and stress cause deterioration through breakdown of actin structure and function. The study addresses poorly understood mechanisms preserving cytoskeletal form and activity by combining a whole-genome CRISPR-Cas9 screen in human fibroblasts with in vivo C. elegans synthetic lethality screening. BET-1 is identified as a key regulator: its overexpression preserves actin function and improves lifespan and healthspan via transcriptional regulation. The work also links BRD4 to senescent survival and reveals dopamine-driven neuron-to-body communication extending lifespan by over 70%, promoting protein homeostasis in an HSF-1-dependent, actin-independent manner.",{"@graph":69,"@context":126},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/more-than-a-loading-control-studying-the-actin-cytoskeleton-for-novel-anti-aging-mechanisms-part/426691/",{"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/more-than-a-loading-control-studying-the-actin-cytoskeleton-for-novel-anti-aging-mechanisms-part/426691.png","ImageObject",300,407,{"name":92,"@type":93},"pop out","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-08","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"Why is actin cytoskeleton function important for aging-related processes?","Question",{"text":112,"@type":113},"Actin function supports multiple cellular pathways, and breakdown of actin cytoskeleton contributes to deterioration of these processes during aging and stress.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What experimental approach was used to identify new regulators of actin health?",{"text":117,"@type":113},"A multi-pronged screen combined a whole-genome CRISPR-Cas9 screen in human fibroblasts with in vivo C. elegans synthetic lethality screening.",{"name":119,"@type":110,"acceptedAnswer":120},"How does overexpression of BET-1 affect longevity?",{"text":121,"@type":113},"Overexpression of BET-1 preserves actin function at late age and increases lifespan and healthspan in C. elegans.",{"name":123,"@type":110,"acceptedAnswer":124},"What signaling mechanism extends lifespan when BET-1 is overexpressed in neurons?",{"text":125,"@type":113},"Neuron-specific overexpression of bet-1 reveals dopamine-driven neuron-to-body communication that extends lifespan by over 70% through actin-independent protein homeostasis in an HSF-1-dependent manner.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},426691,1790742731,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":143,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":67,"update_tm":147,"read_time":24},962090760408,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","540 Innovation in Aging, 2025, Vol. 9, No. S2  \nAbstract citation ID: igaf122.1850  \nMORE THAN A LOADING CONTROL:STUDYING THE ACTIN CYTOSKELETON FOR NOVEL ANTI-AGING MECHANISMS.  \nMaxim Averbukh, Naibedya Dutta, Daniel Hicks, Gilberto Garcia, and Ryo Higuchi-Sanabria, University of Southern California, Los Angeles, California, United States  \nThe actin cytoskeleton is a three-dimensional scaffold of proteins that is a regulatory, energy-consuming network with dynamic properties to shape the structure and function of the cell. Proper actin function is required for many cellular pathways, including cell division, autophagy, chaperone function, endocytosis, and exocytosis. Deterioration of these processes manifests during aging and exposure to stress, which is in part due to the breakdown of the actin cytoskeleton. However, the regulatory mechanisms involved in preservation of cytoskeletal form and function are not well understood.Thus, we performed a multi-pronged, cross-organismal screen combining a whole-genome CRISPR-Cas9 screen in human fibroblasts with in vivo C. elegans synthetic lethality screening to identify novel regulators of actin health. We identified the bromodomain protein, BET-1, as a key regulator of actin function and longevity. Overexpression of bet-1 preserves actin function at late age and promotes lifespan and healthspan in C. elegans. These beneficial effects are mediated through actin preservation by the transcriptional regulator function of BET-1. Interestingly, we also find that BRD4 (homolog of bet-1) is required for senescent cell survival. Interestingly, upon  \nInnovation in Aging, 2025, Vol. 9, No. S2 541  \nneuron-specific overexpression of bet-1, we identified a novel neuron-to-body communication driven by dopamine signaling that extends lifespan by over 70%.This non-autonomous signaling drives peripheral protein homeostasis to drive lifespan in an HSF-1-dependent, but actin-independent mechanism. Together, our discovery assigns a key role for BET-1 in promoting longevity through actin homeostasis when acting autonomously in peripheral tissue, but a unique actin-independent method to promote protein homeostasis when actin non-autonomously through dopaminergic neurons.","cbCaiaq1tCOLuYA2","https://ap.wps.com/l/cbCaiaq1tCOLuYA2","pdf",989501,"English","# Abstract citation ID and title\n## Actin cytoskeleton roles in aging\n## Cross-organism screen strategy\n## BET-1 and actin preservation effects\n## BRD4, senescent cell survival, and neuron-to-body signaling","[{\"question\":\"Why is actin cytoskeleton function important for aging-related processes?\",\"answer\":\"Actin function supports multiple cellular pathways, and breakdown of actin cytoskeleton contributes to deterioration of these processes during aging and stress.\"},{\"question\":\"What experimental approach was used to identify new regulators of actin health?\",\"answer\":\"A multi-pronged screen combined a whole-genome CRISPR-Cas9 screen in human fibroblasts with in vivo C. elegans synthetic lethality screening.\"},{\"question\":\"How does overexpression of BET-1 affect longevity?\",\"answer\":\"Overexpression of BET-1 preserves actin function at late age and increases lifespan and healthspan in C. elegans.\"},{\"question\":\"What signaling mechanism extends lifespan when BET-1 is overexpressed in neurons?\",\"answer\":\"Neuron-specific overexpression of bet-1 reveals dopamine-driven neuron-to-body communication that extends lifespan by over 70% through actin-independent protein homeostasis in an HSF-1-dependent manner.\"}]","MORE THAN A LOADING CONTROL - STUDYING THE ACTIN CYTOSKELETON FOR NOVEL ANTI-AGING MECHANISMS - Part | PDF",1790641465]