Iter-4360dd15-0087-transcript
第 87 轮执行轨迹
→ call search_memory({"limit":10,"query":"4360dd15 原始人类试验 PMID 综述 引用链 主要终点 死亡 生存 健康寿命 失能自由生存"})【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹
→"}, {"title": "Iter-4360dd15-0084-transcript", "tags": "iteration transcript", "modified": "20260424204726000", "preview": "!! 第 84 轮执行轨迹 → cal"}, {"title": "Iter-4360dd15-0085-transcript", "tags": "iteration transcript", "modified": "20260424204857000", "preview": "!! 第 85 轮执行轨迹 → call list_recent({"n":12})
→ call search_memory({"limit":10,"query":"4360dd15 NEXT_FOCUS"})
→ call list_by_tag({"limit":20,"tag":"4360dd15"})
【tool:list_recent】
{"ok": true, "items": [{"title": "Error-20260425-044942", "modified": "20260424204942000", "tags": "error iteration"}, {"title": "Iter-4360dd15-0085-reflection", "modified": "20260424204906000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424204906000", "tags": "pinned focus"}, {"title": "先证终点，再谈长寿", "modified": "20260424204906000", "tags": "lesson endpoint-classification citation-chain trial-audit"}, {"title": "Iter-4360dd15-0085-transcript", "modified": "20260424204857000", "tags": "iteration transcript"}, {"title": "PMID 33977284 is RTI incidence endpoint, not direct longevity evidence", "modified": "20260424204839000", "tags": "4360dd15 fact classification clinical-trials longevity"}, {"title": "Iter-4360dd15-0084-reflection", "modified": "20260424204736000", "tags": "iteration reflection"}, {"title": "线索要尽快落到单个 PMID", "modified": "20260424204736000", "tags": "lesson citation-chain trial-audit endpoint-classification"}, {"title": "Iter-4360dd15-0084-transcript", "modified": "20260424204726000", "tags": "iteration transcript"}, {"title": "PMID 25540326 is immune-response endpoint, not longevity evidence", "modified": "20260424204718000", "tags": "4360dd15 fact classification clinical-trials longevity"}, {"title": "Iter-4360dd15-0083-reflection", "modified": "20260424204557000", "tags": "iteration reflection"}, {"title": "综述只能当入口，不能当证据", "modified": "20260424204557000", "tags": "lesson classification citation-chain trial-audit"}]}
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹
→ call search_memory({\"limit\":10,\"query\":\"4360dd15 NEXT_FOCUS 剩余 10 条候选 PMID 研究类型 保留 排除 理由 extension follow-up secondary analysis\"}) → call list_recent({\"n\":10}) → call list_tools({}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0059-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424195947000\", \"preview\": \"!! 第 59 轮执行轨迹 → call search_memory({\"limit\":10,\"query\":\"4360dd15 NEXT_FOCUS 剩余 10 条候选 PMID 研究类型 保留 排除 理由 extension follow-up secondary analysis\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0055-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424195425000\", \"previe"}, {"title": "Iter-4360dd15-0037-transcript", "tags": "iteration transcript", "modified": "20260424191347000", "preview": "!! 第 37 轮执行轨迹 【tool:list_by_tag】
{"ok": true, "items": [{"title": "PMID 33977284 is RTI incidence endpoint, not direct longevity evidence", "modified": "20260424204839000"}, {"title": "PMID 25540326 is immune-response endpoint, not longevity evidence", "modified": "20260424204718000"}, {"title": "PMID 27883166 is a pilot safety feasibility trial not direct longevity evidence", "modified": "20260424204543000"}, {"title": "PEARL trial is not direct longevity evidence", "modified": "20260424203525000"}, {"title": "Iter-4360dd15-0078-two-pmid-evidence-verification", "modified": "20260424203242000"}, {"title": "Iter-4360dd15-0077-unified-longevity-classification-four-pmids", "modified": "20260424203137000"}, {"title": "Iter-4360dd15-0075-abstract-field-extraction-two-pmids", "modified": "20260424202951000"}, {"title": "Iter-4360dd15-0072-review-exclusion-first-rule", "modified": "20260424202103000"}, {"title": "Iter-4360dd15-0071-minimal-audit-rules", "modified": "20260424201843000"}, {"title": "Iter-4360dd15-0069-standardized-audit-table-two-trials", "modified": "20260424201621000"}, {"title": "Iter-4360dd15-0068-abstract-endpoint-extraction", "modified": "20260424201407000"}, {"title": "Iter-4360dd15-0067-abstract-endpoints-aging-criteria", "modified": "20260424201141000"}, {"title": "Iter-4360dd15-0066-TierA-abstracts-and-endpoints-for-aging-criteria", "modified": "20260424200925000"}, {"title": "Iter-4360dd15-0065-minimal-relevance-decision-rules-for-retained-mtor-trials", "modified": "20260424200748000"}, {"
→ call search_memory({"limit":20,"query":"38310895 reference chain primary trial PMID review mTOR aging human trial"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0001-transcript", "tags": "iteration transcript", "modified": "20260424173243000", "preview": "!! 第 1 轮执行轨迹
→ call search_memory({\"limit\":10,\"query\":\"4360dd15 长生不老 immortality 抗衰老 目标\"}) → call list_recent({\"n\":10}) → call list_tools({}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"GOAL\", \"tags\": \"goal pinned\", \"modified\": \"20260424172208000\", \"preview\": \"[[目标]]：找到让人类长生不老的方法 Mission ID：`4360dd15` 起始时间：2026-04-25T01:22:08 !! 使用说明 这是 Sisyphus 的北极星。永远围绕这个目标展开。 其它 mis"}, {"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹 → cal"}, {"title": "Iter-4360dd15-0011-transcript", "tags": "iteration transcript", "modified": "20260424180153000", "preview": "!! 第 11 轮执行轨迹 → call read_note({"title":"NEXT_FOCUS"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0085）\n\n从综述引用链里锁定 1 个尚未审计的原始人类试验 PMID，并只核实其主要终点是否直接指向死亡、生存、健康寿命或失能自由生存。"}
→ call web_search({"limit":5,"query":"PMID 38310895 mTOR inhibitors ageing review references human trial rapamycin everolimus sirolimus"})
→ call pubmed_search({"limit":10,"query":"38310895 mTOR inhibitors ageing review human trials"})
→ call search_memory({"limit":10,"query":"PMID 38310895 trial references everolimus sirolimus rapamycin"})
【tool:web_search】
{"ok": true, "query": "PMID 38310895 mTOR inhibitors ageing review references human trial rapamycin everolimus sirolimus", "results": [{"title": "Targeting the biology of aging with mTOR inhibitors - Nature", "url": "https://www.nature.com/articles/s43587-023-00416-y", "snippet": "Inhibition of the protein kinase mechanistic target of rapamycin ( mTOR ) with the Food and Drug Administration (FDA)-approved therapeutic rapamycin promotes health and longevity in diverse model ..."}, {"title": "Exploring the role of mTOR pathway in aging and age-related disorders", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12419451/", "snippet": "This extensive review summarizes the most recent findings on mTOR inhibitors in the context of aging, highlighting their complex interactions with cellular systems, effect on longevity, and potential as therapeutic approaches for age-related diseases."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR , a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing -related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved ..."}, {"title": "Rapamycin
【tool:pubmed_search】
{"ok": true, "query": "38310895 mTOR inhibitors ageing review human trials", "results": [{"pmid": "41497909", "title": "The Mechanistic Target of Rapamycin (mTOR) Pathway as a Target of Anti-aging Therapies: The Role of Rapamycin and Its Analogs in the Regulation of Cellular Processes and Their Impact on Longevity.", "source": "Cureus", "pubdate": "2025 Dec", "authors": ["Zerdka J", "Brasse P", "Piszka M", "Kwapien E", "Kubicka M", "Bartkowski J", "Banach J", "Dacyl H"], "url": "https://pubmed.ncbi.nlm.nih.gov/41497909/"}, {"pmid": "41429578", "title": "The Sixth Annual Symposium of the Midwest Aging Consortium.", "source": "J Gerontol A Biol Sci Med Sci", "pubdate": "2026 Feb 5", "authors": ["Sturmlechner I", "Ashiqueali SA", "Martini H", "Valdivieso K", "Franco AC", "Guthikonda P", "Dosch AJ", "Prieto LI"], "url": "https://pubmed.ncbi.nlm.nih.gov/41429578/"}, {"pmid": "41096951", "title": "Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.", "source": "Int J Mol Sci", "pubdate": "2025 Oct 4", "authors": ["Ozdemir SA", "Faizan MI", "Kaur G", "Shaikh SB", "Ul Islam K", "Rahman I"], "url": "https://pubmed.ncbi.nlm.nih.gov/41096951/"}, {"pmid": "41096641", "title": "Rewinding the Clock: Emerging Pharmacological Strategies for Human Anti-Aging Therapy.", "source": "Int J Mol Sci", "pubdate": "2025 Sep 25", "authors": ["Delrue C", "Speeckaert R", "Speeckaert MM"], "url": "https://pubmed.ncbi.nlm.nih.gov/41096641/"}, {"
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0040-transcript", "tags": "iteration transcript", "modified": "20260424192058000", "preview": "!! 第 40 轮执行轨迹
→ call search_memory({\"limit\":10,\"query\":\"4360dd15 PMID 38310895 rapalog trial human trial 14 candidate 11 remaining\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0010-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424175830000\", \"preview\": \"!! 第 10 "}, {"title": "Iter-4360dd15-0038-transcript", "tags": "iteration transcript", "modified": "20260424191624000", "preview": "!! 第 38 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin mTOR systematic review 2024 trial endpoint PMC table remaining included studies\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\ → call web_fetch({"max_chars":7000,"url":"https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call pubmed_search({"limit":20,"query":"37142830 rapamycin trial PMID elderly health span immune function abstract"})
→ call web_search({"limit":10,"query":"site:pubmed.ncbi.nlm.nih.gov rapamycin elderly trial PMID health span immune function everolimus"})
→ call search_memory({"limit":10,"query":"4360dd15 PMID trial rapamycin elderly immune function physical performance cognition"})
【tool:pubmed_search】
{"ok": true, "query": "37142830 rapamycin trial PMID elderly health span immune function abstract", "results": []}
【tool:web_search】
{"ok": true, "query": "site:pubmed.ncbi.nlm.nih.gov rapamycin elderly trial PMID health span immune function everolimus", "results": [{"title": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/", "snippet": "PubMed® comprises more than 40 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites ."}, {"title": "The effect of rapamycin and its analogues on age-related ...", "url": "https://pubmed.ncbi.nlm.nih.gov/35861940/", "snippet": "The effect of rapamycin and other rapalogues, including everolimus and temsirolimus, on bone, muscle and joints have been evaluated in humans; however, considerable variability concerning the subjects' age, inclusion criteria, and drug administration protocols was identified."}, {"title": "Blazing a trail for the clinical use of rapamycin as a ... - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/37801202/", "snippet": "Concerns over the risk of potentially serious side effects in humans, including immunosuppression and metabolic disruptions, have cautiously limited the translation of rapamycin and its analogs as a treatment for aging associated conditions."}, {"title": "Intermittent rapamycin feeding recapitulates some effects of continuous ...", "url": "https://pubmed.ncbi.nlm.nih.gov/38360109/", "snippet": "Intermittent rapamycin treatment is effective in prolonging lifespan and reduces some side-effect
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0083-transcript", "tags": "iteration transcript", "modified": "20260424204550000", "preview": "!! 第 83 轮执行轨迹
→ call search_"}, {"title": "Iter-4360dd15-0084-transcript", "tags": "iteration transcript", "modified": "20260424204726000", "preview": "!! 第 84 轮执行轨迹 → cal"}, {"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹 → call web_search({"limit":10,"query":"site:pubmed.ncbi.nlm.nih.gov rapamycin older humans randomized trial PMID vaccine response everolimus"})
→ call arxiv_search({"limit":5,"query":"rapamycin humans trial aging healthspan PMID"})
→ call web_search({"limit":10,"query":"\"everolimus\" older humans trial PMID immune function"})
→ call web_search({"limit":10,"query":"\"rapamycin\" elderly trial PMID physical performance cognition"})
→ call web_search({"limit":10,"query":"\"sirolimus\" human trial elderly PMID healthspan"})
【tool:web_search】
{"ok": true, "query": "site:pubmed.ncbi.nlm.nih.gov rapamycin older humans randomized trial PMID vaccine response everolimus", "results": [{"title": "The effect of rapamycin and its analogues on age-related ...", "url": "https://pubmed.ncbi.nlm.nih.gov/35861940/", "snippet": "The effect of rapamycin and other rapalogues, including everolimus and temsirolimus, on bone, muscle and joints have been evaluated in humans ; however, considerable variability concerning the subjects' age, inclusion criteria, and drug administration protocols was identified."}, {"title": "Checking your browser - reCAPTCHA - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/29408453/", "snippet": "Checking your browser before accessing pubmed.ncbi.nlm.nih.gov ..."}, {"title": "Dose-Dependent Acute Effects of Everolimus Administration on ...", "url": "https://pubmed.ncbi.nlm.nih.gov/32475067/", "snippet": "Abstract The rapamycin analogue everolimus (EVR) is a potent inhibitor of the mammalian target of rapamycin (mTOR) and clinically used to prevent allograft rejections as well as tumor growth. The pharmacokinetic and immunosuppressive efficacy of EVR have been extensively reported in patient populations and in vitro studies. However, dose-dependent ex vivo effects upon acute EVR administration ..."}, {"title": "Rejuvenating immunity: \"anti-aging drug today\" eight years later", "url": "https://pubmed.ncbi.nlm.nih.gov/25844603/", "snippet": "The 2014 year ended with celebration: Everolimus , a rapam
【tool:arxiv_search】
{"ok": true, "query": "rapamycin humans trial aging healthspan PMID", "results": [{"title": "Implications of Aging in Bacteria", "authors": ["Leah R. Johnson", "Marc Mangel"], "published": "2005-09-30", "summary": "Motivated by recent research of aging in E. coli, we explore the effects of aging on bacterial fitness. The disposable soma theory of aging was developed to explain how differences in lifespans and aging rates could be linked to life history trade-offs. Although generally applied for multicellular organisms, it is also useful for exploring life history strategies of single celled organisms such as bacteria. Starting from the Euler-Lotka equation, we propose a mathematical model to explore how a finite lifespan effects fitness of bacteria. We find that that there is surprisingly little loss of fitness when the bacterium has limited opportunities to reproduce. Instead, the fitness gained each time the bacteria reproduces decreases rapidly, and investing resources to survive to reproduce the first few times is likely more advantageous than investing additional resources to try to maintain cell integrity longer.", "url": "https://arxiv.org/abs/q-bio/0510001v1"}, {"title": "DNA methylation markers to assess biological age", "authors": ["Dmitriy I. Podolskiy", "Vadim N. Gladyshev"], "published": "2018-11-14", "summary": "Among the different biomarkers of aging based on omics and clinical data, DNA methylation clocks stand apart providing unmatched accuracy in assessing t
【tool:web_search】
{"ok": true, "query": "\"everolimus\" older humans trial PMID immune function", "results": []}
【tool:web_search】
{"ok": true, "query": "\"rapamycin\" elderly trial PMID physical performance cognition", "results": []}
【tool:web_search】
{"ok": true, "query": "\"sirolimus\" human trial elderly PMID healthspan", "results": []}
→ call web_search({"limit":10,"query":"\"35861940\" rapamycin analogues age-related review trial PMID human"})
→ call search_memory({"limit":10,"query":"35861940 trial PMID rapamycin analogues age-related review human"})
→ call pubmed_search({"limit":20,"query":"35861940 rapamycin analogues age-related review trial"})
【tool:web_search】
{"ok": true, "query": "\"35861940\" rapamycin analogues age-related review trial PMID human", "results": []}
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0009-transcript", "tags": "iteration transcript", "modified": "20260424175555000", "preview": "!! 第 9 轮执行轨迹
→ call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin mTOR systematic review 2024 trial endpoint PMC table remaining included studies\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\""}, {"title": "Iter-4360dd15-0011-transcript", "tags": "iteration transcript", "modified": "20260424180153000", "preview": "!! 第 11 轮执行轨迹 → call search_memory({\\\"limit\\"}, {"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹 【tool:pubmed_search】
{"ok": true, "query": "35861940 rapamycin analogues age-related review trial", "results": [{"pmid": "41497909", "title": "The Mechanistic Target of Rapamycin (mTOR) Pathway as a Target of Anti-aging Therapies: The Role of Rapamycin and Its Analogs in the Regulation of Cellular Processes and Their Impact on Longevity.", "source": "Cureus", "pubdate": "2025 Dec", "authors": ["Zerdka J", "Brasse P", "Piszka M", "Kwapien E", "Kubicka M", "Bartkowski J", "Banach J", "Dacyl H"], "url": "https://pubmed.ncbi.nlm.nih.gov/41497909/"}, {"pmid": "37571296", "title": "Epigallocatechin-3-Gallate, an Active Green Tea Component to Support Anti-VEGFA Therapy in Wet Age-Related Macular Degeneration.", "source": "Nutrients", "pubdate": "2023 Jul 28", "authors": ["Blasiak J", "Chojnacki J", "Szczepanska J", "Fila M", "Chojnacki C", "Kaarniranta K", "Pawlowska E"], "url": "https:
```