{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:11:40Z","timestamp":1788757900478,"version":"build-2803163510"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:p>\n                    Twentieth-century medicine was most successful against diseases sharing a particular causal architecture: a discrete lesion standing in a relation of approximate necessity and sufficiency to a clinical syndrome, amenable to specific perturbation. Mortality from acute myocardial infarction has fallen by nearly 90 percent in the United States since 1970; pediatric leukemia has become survivable; HIV has become chronic. That success has shifted the residual burden toward conditions with a different architecture\u2014late-life neurodegeneration, multimorbidity, frailty, idiopathic neuropathy\u2014in which pathology is distributed across scales, and no single node carries the necessity that targeted intervention requires. The failure is not that medicine has extended life. It is that biomedical institutions have not adapted to the forms of vulnerability that accompany longer lives, and the non-adaptation is structural rather than accidental. This paper asks why: why funding and evaluation systems systematically favor research on discrete diseases and individual molecular targets over integrated research on aging as a systemic, multiscale, temporally extended process. We distinguish two levels at which the apparatus fragments its object.\n                    <jats:italic>First-order fragmentation<\/jats:italic>\n                    partitions aging into separately funded age-related diseases.\n                    <jats:italic>Second-order fragmentation<\/jats:italic>\n                    partitions aging itself into hallmarks, pathways, and targets pursued independently\u2014which is why geroscience, the framework formulated to unify the age-related diseases, is decomposed by the apparatus that funds it. We specify the funding signatures each level of fragmentation predicts\u2014across award duration, award mechanism, intervention modality, and the ratio of disease-specific to process-directed funding\u2014and identify the data that would test them; we distinguish the several senses of reductionism at issue, defending integrative explanatory pluralism rather than holism; and we assess whether the hallmarks framework supports integration or licenses a longer list of targets. The argument is that the conceptual case for a multiscale account of late-life disease has been adequately made, and what remains unbuilt is institutional.\n                  <\/jats:p>","DOI":"10.3389\/fpubh.2026.1932205","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T04:24:00Z","timestamp":1788755040000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The success-failure inversion in modern medicine"],"prefix":"10.3389","volume":"14","author":[{"given":"Madhur","family":"Mangalam","sequence":"first","affiliation":[{"name":"Department of Biomechanics, University of Nebraska at Omaha","place":["Omaha, NE, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Fabianiak","sequence":"additional","affiliation":[{"name":"Department of Biomechanics, University of Nebraska at Omaha","place":["Omaha, NE, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Cense","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science, University of Nebraska Medical Center","place":["Omaha, NE, United States"]},{"name":"Department of Electrical, Electronic and Computer Engineering, University of Western Australia","place":["Perth, WA, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1161\/CIRCRESAHA.116.309115","article-title":"Decline in cardiovascular mortality: possible causes and implications","volume":"120","author":"Mensah","year":"2017","journal-title":"Circ Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1056\/NEJMsa053935","article-title":"Explaining the decrease in US deaths from coronary disease","volume":"356","author":"Ford","year":"2007","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e038644","DOI":"10.1161\/JAHA.124.038644","article-title":"Heart disease mortality in the United States","volume":"14","author":"King","year":"2025","journal-title":"J Am Heart Assoc"},{"key":"B4","first-page":"649","article-title":"Decline in deaths from heart disease and stroke\u2013United States, 1900-1999","volume":"48","year":"1999","journal-title":"MMWR Morb Mortal Wly Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1056\/NEJMra1400972","article-title":"Acute lymphoblastic leukemia in children","volume":"373","author":"Hunger","year":"2015","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/S2352-4642(18)30066-X","article-title":"Global efforts toward the cure of childhood acute lymphoblastic leukaemia","volume":"2","author":"Pui","year":"2018","journal-title":"Lancet Child Adoles Health"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e207954","DOI":"10.1001\/jamanetworkopen.2020.7954","article-title":"Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000-2016","volume":"3","author":"Marcus","year":"2020","journal-title":"JAMA Netw Open"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e349","DOI":"10.1016\/S2352-3018(17)30066-8","article-title":"Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies","volume":"4","author":"Trickey","year":"2017","journal-title":"The Lancet HIV"},{"key":"B9","first-page":"251","article-title":"The internal secretion of the pancreas","volume":"125","author":"Banting","year":"2007","journal-title":"Indian J Med Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.2337\/dci16-0055","article-title":"The changing tides of the type 2 diabetes epidemic\u2013smooth sailing or troubled waters ahead? 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