[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-447636-105":59,"doc-detail-447636-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","how-aging-causes-osteoarthritis-an-evolutionary-physiology-perspective","How aging causes osteoarthritis: an evolutionary physiology perspective","","Late-life diseases result from poorly understood senescence processes largely determined by genetics. An evolutionary physiology-based multifactorial model proposes that non-adaptive programmatic mechanisms encoded by the normal (wild-type) genome interact with disruptions to wild-type function from causes such as pathogens, mechanical injury, and malnutrition. Osteoarthritis (OA) is explored as a complex test case and framed via a futile endochondral ossification quasi-program in which hypertrophic articular chondrocytes reshape joint architecture. Programmatic priming can be triggered by secondary OA causes, with antagonistic pleiotropy suggested to balance early repair benefits against late costs.",{"@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/how-aging-causes-osteoarthritis-an-evolutionary-physiology-perspective/447636/",{"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/how-aging-causes-osteoarthritis-an-evolutionary-physiology-perspective/447636.png","ImageObject",300,407,{"name":92,"@type":93},"dawugda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What does the multifactorial model propose about why senescence leads to late-life disease?","Question",{"text":113,"@type":114},"It proposes that evolved but non-adaptive programmatic mechanisms encoded by the wild-type genome combine with disruptions to wild-type function from factors like pathogens, mechanical injury, and malnutrition in various combinations.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does the framework explain the core mechanism of osteoarthritis (OA)?",{"text":118,"@type":114},"The core OA mechanism is described as a futile endochondral ossification quasi-program, where hypertrophic articular chondrocytes alter joint architecture.",{"name":120,"@type":111,"acceptedAnswer":121},"What is the suggested evolutionary cause of priming chondrocytes for quasi-program activation?",{"text":122,"@type":114},"Selection for early-life tissue repair benefits at the expense of late-life programmatic costs is suggested, involving antagonistic pleiotropy.","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},447636,1791115032,{"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":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},3985747870947,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Europe PMC unders uthManuscripts Europe M eC und Author Manuscripts  \n| Europe PMC Funders Group\u003Cbr>Author Manuscript\u003Cbr>Osteoarthritis Cartilage. Author manuscript; available in PMC 2026 January 06. |\n| --- |\n| Published in final edited form as:\u003Cbr>Osteoarthritis Cartilage. 2025 August 01; 33(8): 921–932. doi:10.1016/j.joca.2025.05.001 .\u003Cbr>How aging causes osteoarthritis: an evolutionary physiology perspective\u003Cbr>David Gems\u003Cbr>Institute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.\u003Cbr>Abstract\u003Cbr>Late-life diseases result from the poorly understood process of senescence (aging), that is largely genetically determined. According to a recently proposed evolutionary physiology-based account, the multifactorial model, senescence is largely caused by evolved but non-adaptive programmatic mechanisms specified by the wild-type (i.e. normal) genome. These act together with disruptions to wild-type function (due e.g. to infectious pathogens, mechanical injury and malnutrition) ina variety of combinations to generate diverse late-life diseases. Here the utility of this model is explored by testing its capacity to provide an account of one complex, late-life disease, osteoarthritis (OA), and a framework for understanding OA etiology suggested. In this framework, the core OA disease mechanism is a futile endochondral ossification quasi-program (non-adaptive developmental program), in which hypertrophic articular chondrocytes alter joint architecture.\u003Cbr>Programmatic changes prime chondrocytes for quasi-program activation, which can be triggered by secondary causes of OA (e.g. joint mechanical injury) . A suggested evolutionary cause of this priming, involving antagonistic pleiotropy, is selection to maximize early life tissue repair benefits at the expense of late-life programmatic costs.\u003Cbr>Keywords\u003Cbr>antagonistic pleiotropy; chondrocyte; evolutionary medicine; hyperfunction; osteoarthritis;\u003Cbr>programmatic theory\u003Cbr>Introduction\u003Cbr>“The physician is constantly referring to the biologist for a scientific basis for geriatrics, and finding that it is not there”(Comfort, 1979)\u003Cbr>The biological process of senescence (aging) remains poorly defined and, consequently, our understanding of late-life disease etiologies remains far from complete. Arguably, the main purpose of biogerontology, the study of the biology of aging, is to provide an account of the mechanisms of senescence in terms of general principles, that can guide research on late-life\u003Cbr>This work is licensed under a BY 4.0 International license.\u003Cbr>Correspondence to: David Gems.\u003Cbr>Corresponding author: David Gems, Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment University College London, Gower Street, London WC1E 6BT, United Kingdom, david gems@ucl ac uk |\n\nEurope PMC unders uthManuscripts Europe M eC und Author Manuscripts  \nGems Page 2  \ndisease (Comfort, 1979) . However, thus far such accounts have remained fragmentary, and with only limited capacity to do so (Gems and de Magalhães, 2021; Gems et al., 2024a) .  \nHowever, recent years have seen the emergence of a promising evolutionary physiologybased conceptual framework that combines evolutionary and proximate mechanisms to explain the causes of aging. This framework includes the evolutionary theory of aging (Arnold and Rose, 2023; Williams, 1957), the hyperfunction (or developmental) theory of aging (Blagosklonny, 2006; de Magalhães and Church, 2005), among other programmatic mechanisms (Gems and Kern, 2024), and a multifactorial model of the origins of late-life diseases (Gems, 2022) .  \nIn this article, the capacity of the multifactorial model to explain a test-case complex  \nlate-life disease, osteoarthritis, is investigated. To do this, a conceptual research approach has been used, where an existing theory is tested by examining and repurposing existing published findings (Blagosklonny and Pardee, 20","cbCaihwa7YM8e07R","https://ap.wps.com/l/cbCaihwa7YM8e07R","pdf",1520342,27,"English","# Abstract\n# Introduction\n# The multifactorial model\n## Evolutionary theory of aging\n## Programmatic theories and proximate mechanisms","[{\"question\":\"What does the multifactorial model propose about why senescence leads to late-life disease?\",\"answer\":\"It proposes that evolved but non-adaptive programmatic mechanisms encoded by the wild-type genome combine with disruptions to wild-type function from factors like pathogens, mechanical injury, and malnutrition in various combinations.\"},{\"question\":\"How does the framework explain the core mechanism of osteoarthritis (OA)?\",\"answer\":\"The core OA mechanism is described as a futile endochondral ossification quasi-program, where hypertrophic articular chondrocytes alter joint architecture.\"},{\"question\":\"What is the suggested evolutionary cause of priming chondrocytes for quasi-program activation?\",\"answer\":\"Selection for early-life tissue repair benefits at the expense of late-life programmatic costs is suggested, involving antagonistic pleiotropy.\"}]","How aging causes osteoarthritis: an evolutionary physiology perspective | PDF",1790721994,68]