[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-421532-105":59,"doc-detail-421532-en":124},{"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":117,"head_meta":119,"extra_data":121,"updated_unix":123},105,"en","testing-the-translational-potential-of-rapamycin-on-healthy-aging","Testing the Translational Potential of Rapamycin on Healthy Aging","","Treatment with rapamycin, an mTORC1 inhibitor, has repeatedly been shown to extend lifespan and reduce or delay age-related diseases across diverse model systems. Clinical use has been constrained by concerns about adverse effects, including immunosuppression and metabolic disruptions, even as some physically active adults take rapamycin off-label to extend healthspan. Evidence suggests negative effects may relate to mTORC2 inhibition, motivating intermittent dosing or more selective rapalogs. Human clinical trial design, safety, PK/PD, and efficacy evaluation remain uncertain, as does how dosing schedules modify health benefits from exercise. This work reports rationale and updates for two ongoing trials and integrates multi-omics findings in older mice to inform future clinical trial design.",{"@graph":69,"@context":116},[70,84,99],{"@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/testing-the-translational-potential-of-rapamycin-on-healthy-aging/421532/",{"url":83,"name":65,"@type":85,"author":86,"headline":65,"publisher":89,"fileFormat":92,"inLanguage":63,"description":67,"dateModified":93,"datePublished":93,"encodingFormat":92,"isAccessibleForFree":94,"interactionStatistic":95},"DigitalDocument",{"name":87,"@type":88},"Maya Linwood","Person",{"url":74,"name":90,"@type":91},"DocShare","Organization","application/pdf","2026-09-28",true,{"@type":96,"interactionType":97,"userInteractionCount":4},"InteractionCounter",{"@type":98},"ViewAction",{"@type":100,"mainEntity":101},"FAQPage",[102,108,112],{"name":103,"@type":104,"acceptedAnswer":105},"Why has rapamycin’s clinical translation for healthy aging been limited?","Question",{"text":106,"@type":107},"Despite benefits in model systems, clinical translation has been constrained by risks such as immunosuppression and metabolic disruptions.","Answer",{"name":109,"@type":104,"acceptedAnswer":110},"What role might mTORC2 play in rapamycin-related negative side effects?",{"text":111,"@type":107},"A working model suggests that while mTORC1 inhibition supports healthy aging, many adverse effects are associated with inhibition of the second complex, mTORC2.",{"name":113,"@type":104,"acceptedAnswer":114},"How does this research plan to evaluate rapamycin dosing schedules in humans and models?",{"text":115,"@type":107},"It provides rationale and updates for two ongoing human clinical trials assessing safety, pharmacokinetics, pharmacodynamics, and efficacy, and it adds multi-omics findings from older mice to examine exercise-related molecular and metabolic adaptations.","https://schema.org",{"og:url":83,"og:type":118,"og:title":65,"og:site_name":90,"og:description":67},"article",{"robots":120,"canonical":83},"index,follow",{"doc_id":122,"site_id":62},421532,1790625079,{"code":4,"msg":5,"data":125},{"doc_id":122,"user_id":126,"nickname":87,"user_avatar":127,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":128,"file_id":129,"file_url":130,"file_type":131,"file_size":132,"view_count":4,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":133,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":134,"faqs":135,"seo_title":136,"seo_description":67,"update_tm":123,"read_time":24},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","122 Innovation in Aging, 2025, Vol. 9, No. S2  \nAbstract citation ID: igaf122.406  \nTESTING THE TRANSLATIONAL POTENTIAL OF RAPAMYCIN ON HEALTHY AGING  \nAdam Konopka, University of Wisconsin-Madison  \nTreatment with rapamycin, an inhibitor of the mechanistic Target Of Rapamycin Complex One (mTORC1) protein kinase, has been repeatedly demonstrated to extend lifespan and prevent or delay several age-related diseases in diverse model systems. Concerns over the risk of adverse side effects, including immunosuppression and metabolic disruptions, have cautiously limited the clinical translation of rapamycin and its analogs as a treatment for aging associated conditions. Despite potential risks, an increasing number of physically active adults are taking themTOR inhibitor rapamycin off label with the goal of extending healthspan. A working model suggests that while inhibition of mTORC1 promotes healthy aging, many of the negative side effects of rapamycin are associated with inhibition of a second mTOR complex, mTORC2 . Differences in the kinetics and molecular mechanisms by which rapamycin inhibits mTORC1 and mTORC2 suggest that a therapeutic window for rapamycin could be exploited using intermittent dosing schedules or alternative rapalogs that may enable more selective inhibition of mTORC1 . However, the optimal dosing schedules and the long-term efficacy of such interventions in humans is unknown. Further, it remains unknown how different rapamycin dosing schedules impact the health benefits of exercise. Here, I will provide the rationale, experimental design, and updates for two ongoing human clinical trials aimed to determine the safety, pharmacokinetics, pharmacodynamics, and efficacy of rapamycin and rapalogs on several clinically oriented outcomes. I will also share new insights from integrated multi-omics studies that reveal the impact of different rapamycin dosing schedules on the molecular and metabolic adaptations to exercise in older mice. Results from these pre-clinical and early phase studies will help  \nInnovation in Aging, 2025, Vol. 9, No. S2 123  \nguide the design of future clinical trials to determine whether rapamycin can be used safely to inhibit mTORC1 for the treatment and prevention of age-related diseases in humans.","cbCaibGx7lfTig0j","https://ap.wps.com/l/cbCaibGx7lfTig0j","pdf",270086,"English","# Testing the Translational Potential of Rapamycin on Healthy Aging\n## Rationale and concerns for clinical translation\n## Proposed strategy: mTORC1-selective inhibition and dosing schedules\n## Ongoing human clinical trials (safety, PK/PD, efficacy)\n## Multi-omics insights from older-mouse exercise adaptations\n## Implications for future human trial design","[{\"question\":\"Why has rapamycin’s clinical translation for healthy aging been limited?\",\"answer\":\"Despite benefits in model systems, clinical translation has been constrained by risks such as immunosuppression and metabolic disruptions.\"},{\"question\":\"What role might mTORC2 play in rapamycin-related negative side effects?\",\"answer\":\"A working model suggests that while mTORC1 inhibition supports healthy aging, many adverse effects are associated with inhibition of the second complex, mTORC2.\"},{\"question\":\"How does this research plan to evaluate rapamycin dosing schedules in humans and models?\",\"answer\":\"It provides rationale and updates for two ongoing human clinical trials assessing safety, pharmacokinetics, pharmacodynamics, and efficacy, and it adds multi-omics findings from older mice to examine exercise-related molecular and metabolic adaptations.\"}]","Testing the Translational Potential of Rapamycin on Healthy Aging | PDF"]