What is a Disease? | Ruslav Medzhitov | ISEMPH

Human diseases are highly heterogeneous in terms of epidemiology, age-dependence, chronicity, recovery and mortality rates. This heterogeneity reflects different causalities of diseases. There is no comprehensive system of disease classification currently available that reflects fundamental causalities of human diseases. The distinction between proximal and ultimate causations is useful but insufficient to reflect the underlying biological and evolutionary bases of disease diversity. Dr. Medzhitov will discuss human diseases from several evolutionary biological perspectives to suggest a framework of diseases classification that is based on fundamental causalities. Different disease categories reflect distinct underlying biological processes and mechanisms and account for the changing spectrum of human diseases. This framework may also be useful for considering devel- opment of different therapeutic approaches. Ruslan Medzhitov obtained his undergraduate degree from Tashkent State University in 1990 and his doctoral degree from Moscow State University in 1993. He began his career as a visiting student at the University of California, San Diego, and in 1994, he became a postdoctoral associate with Howard Hughes Medical Institute working with Dr. Charles A. Janeway, Jr., at Yale University School of Medicine. Medzhitov became an assistant professor in 1999 at Yale University School of Medicine in the section of immunobiology. He is currently the David W. Wallace Professor of Immunobiology at Yale University School of Medicine and an investigator of the Howard Hughes Medical Institute. His research interests include biology of inflammation, innate immunity, mechanisms of allergic reactions, cell signaling and gene regulation. Medzhitov is a member of the National Academy of Sciences, Institute of Medicine, and European Molecular Biology Organization, and he is a fellow of the American Academy of Microbiology.
“What is a disease?”
Ruslan Medzhitov, Ph.D
Yale University School of Medicine, Howard Hughes Medical Institute
Yale University

[@M.-.D]

Professor Medzhitov presents the ideas so clearly. Amazing contributions to the field of medicine and biology.

[@rhyothemisprinceps1617]

9:13 Robustness, resilience and vulnerability 15:45 Anna Karenina Principle in Life History Theory - only one way an environment can be perfect and many ways it can be hostile 16:00 Homeostasis - Maintenance - Defense 17:58 taking out the garbage is not part of homeostasis, it's a function of maintenance 20:24 Extrinsic and Intrinsic Mortality - investment in maintenance programs is dictated by extrinsic mortality rates 32:00 systems that have adjustable set points are vulnerable to dysregulation example: insulin signalling pathway - change in glucose allocation to fetus in pregnancy or to immune system in infection "That built-in property to change the set point of the insulin system also makes it vulnerable to type 2 diabetes and other diseases. ... Not all systems are vulnerable to diseases of homeostatis, only [those] with adjustable homeostatic set points." 33:32 Category 5 - Diseases caused by lack of maintenance -- all age-related diseases - consequence of antagonistic pleiotropy - maintenance mechanisms are not studied as such (e.g., DNA repair) - diseases that are preventable but not naturally curable, e.g., most cancers, neurodegenerative diseases, type 2 diabetes 39:00 Summary 42:16 Q&A - Is aging a disease? 42:59 anagonistic pleitropy vs. mutation accumulation 43:47 the categories are not unique [mutually exclusive?] - same disease can arise due to different causalities

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