Ontology of Aging (August 2014)

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Increasingly, biological and clinical scientists are using ontologies to serve integration and coordination of research across diverse organisms and scientific fields. Ontologies, in this context, are …

Increasingly, biological and clinical scientists are using ontologies to serve integration and coordination of research across diverse organisms and scientific fields. Ontologies, in this context, are logically organized collections of terms defined in such a way that they can be used consistently across multiple disciplines to describe clinical and experimental data. Ontologies are used in aging research to unify experimental results from a broad range of fields including genetics, proteomics, (stem) cell biology, oncology, model organism biology, psychogerontology, and many more. We will explore against this background questions such as the following: What is aging? What is premature aging? And more specifically: Is aging a disease?

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  • http://en.wikipedia.org/wiki/Immortality
  • http://sigpubs.biostr.washington.edu/archive/00000204/
  • http://upload.wikimedia.org/wikipedia/commons/5/5b/Human_Fertilization.png
  • http://blog.botanybill.info/?p=1225

Transcript

  • 1. Ontology of Aging Barry Smith http://ontology.buffalo.edu/smith August 2, 2014 1
  • 2. A good theory of disease requires a good theory of aging 1. Problem: Are the characteristic ‘diseases of old age’ really diseases? 2. Philosophers’ theories of disease (and aging) should be consistent with what is known scientifically about the biological processes involved. 3. Our approach should cover organisms in all multicellular species which die as a result of aging. (This means practically all species, except perhaps hydra, and certain species of jellyfish and pine tree.*) 4. It should apply to normal cases of aging (not: science fiction cases, not cases involving interference by laboratory equipment or an ICU, not cases involving genetic mutations). Q. Where can we find information about the biology of disease and aging that is useful to philosophers (and that in principle allows philosophers to make a contribution to its further development)? 2
  • 3. Ontology •as branch of philosophy 3
  • 4. Ontology •as branch of philosophy •as computer/engineering discipline, whose most conspicuous successes are in the field of bioinformatics 4
  • 5. The world’s most successful ontology 5
  • 6. The world’s most successful ontology 6
  • 7. http://www.ebi.ac.uk/QuickGO/GSearch?q=aging 7
  • 8. 8
  • 9. 9
  • 10. 10 Axioms
  • 11. 11
  • 12. Unified science reborn recall the Vienna circle ideal of unifying science via first order logic GO = a set of terms, definitions and axioms (using resources from first order logic) associated with gigantic bodies of real scientific data (terms used for tagging the data) 12
  • 13. 13
  • 14. 14
  • 15. Ontology axioms for aging (samples, from GO) • multicellular organism aging is_a aging • aging is_a biological process • multicellular organism aging part_of multicellular organism development 15
  • 16. Ontology axioms (dying) •dying part_of life of organism •life of organism occupies temporal interval •dying has_participant organism •dying occupies temporal interval 16
  • 17. Ontology axioms – universal truths 1. dying occupies temporal interval 2. every dying instance_of process 3. every process occupies some temporal interval 1. is an assertion about types or universals* 2. is an assertion about a relation between types and instances 3. is an assertion about instances *what ontology graphs represent 17
  • 18. 18
  • 19. We know when dying ends 19 Death Process boundaries Instants of Time occupy Dying
  • 20. When does dying begin? 20 Death Process boundaries Instants of Time occupy Dying
  • 21. When does balding begin? 21
  • 22. An ontological question: what is aging? 22 The Aging Process Death Processes in the Organism Regions of Time occupy The Dying Process Life of Organism
  • 23. Orthomereology 23 The Aging Process Death Processes in the Organism Regions of Time occupy The Dying Process (Normal) life of (normal) multicellular organism
  • 24. Aging part_of life of organism 24 – Every instance of aging part_of life of some organism NOT: aging has_part dying – given progeria NOT: Life of organism has_part aging (a) a life may be cut short by early death (b) rejuvenation
  • 25. http://www.sens.org/ 26
  • 26. We focus in what follows on ‘normal aging’? = non-premature aging which is not cut short by early death There are certain processes which are normally part of the aging process 27
  • 27. Carlos Lopez-Otin, et al., “The Hallmarks of Aging”, Cell 153, 2013 28
  • 28. Of the roughly 150,000 people who die each day across the globe, about two thirds die of age-related causes (senescence) Hypothesis: age-related causes =def. processes of a sort which (i) are part of the normal aging process and (ii) occur at the stage in life that is normal for aging 29
  • 29. What does ‘normal’ mean? For anatomy we have an answer to this question 30
  • 30. Foundational Model of Anatomy 31 Canonically (normally) human beings have 32 teeth • This is part of the Bauplan of human beings • US adults have an average of 24.92 teeth • Thus ‘normal’  ‘statistically normal’
  • 31. 32 represents canonical adult human anatomy = the Bauplan generated by the coordinated expression of the human organism’s own structural genes* *thus there is still a statistical dimension here, but not at the level of patient phenotypes (teeth lost in bar fights) Foundational Model of Anatomy Ontology
  • 32. Foundational Model of Anatomy (FMA) Pleural Cavity Interlobar recess Mesothelium of Pleura Pleura(Wall of Sac) Visceral Pleura Pleural Sac Parietal Pleura Anatomical Space Organ Cavity Serous Sac Cavity Anatomical Structure Organ Serous Sac Mediastinal Pleura Tissue Organ Part Organ Subdivision Organ Component Organ Cavity Subdivision Serous Sac Cavity Subdivision 33
  • 33. Canonically (normally) human beings have 2 lungs • This is part of the Bauplan of human beings Canonically (normally) death is the terminal boundary of a process of aging • This is part of the life plan of human beings 34
  • 34. What makes premature aging non-normal? Answer: that it does not fit in the right way into the life plan for an organism of the relevant type It does not fit into the canonical cycle of stages generated by the coordinated expression of the organism’s own developmental genes 35
  • 35. 36 Life plan (human, first 9 days)
  • 36. From anatomy to development •Canonical Bauplan = no amputation stumps, no effects of steroids, no webbed fingers … •Canonical life plan = canonical sequence of life processes for an organism of this species (no early death through injury or famine, no life-changing childhood disease, no excessive studying of philosophy …) - 37
  • 37. Where do we find a good ontology of stages? 38
  • 38. In the life cycle of plants we have alternating generations gametophyte = whole plant in haploid stage; male and female gametes fuse to produce the zygote from which the sporophyte arises sporophyte = whole plant in diploid stage (the dominant form in vascular plants such as ferns); produces spores from which the gametophyte arises. whole plant development stage PO:0007033 gametophyte development stage PO:0028003 sporophyte development stage PO:0028002 life of whole plant PO:0025337 PP 39
  • 39. Life cycle of Selaginella apoda (Felsen Moosfarn) 40
  • 40. whole plant development stage PO:0007033 gametophyte development stage PO:0028003 sporophyte development stage PO:0028002 life of whole plant PO:0025337 plant spore stage PO:0025375 gametophyte vegetative stage PO:0025340 gametophyte dormant stage PO:0025342 gametophyte reproductive stage PO:0025341 gametophyte senescent stage PO:0025343 sporophyte senescent stage PO:0007017 sporophyte dormant stage PO:0007132 sporophyte reproductive stage PO:0007130 sporophyte vegetative stage PO:0007134 plant zygote stage PO:0028002 PP is_a part_ of 41 Plant Life Cycle (principal whole plant development stages)
  • 41. 42http://blog.botanybill.info/?p=1225 sporophyte senescent stage PO:0007017
  • 42. Senescence for whole plants does not imply senescence for plant parts often fruit development on a whole plant is happening simultaneously with senescence of the plant in some cases, fruit doesn’t ripen until after the vegetative parts of the plant are dead 43
  • 43. 44 http://bioportal.bioontology.org
  • 44. Canonical whole (human) organism stages 45 whole human development stage post-natal development stage aging stage reproductive stage maturation stage growth stage P life of whole human pre-natal development stage morula stage embryo stage zygote stage P blastula stage gastrula stage
  • 45. From birth to death 46 whole human development stage post-natal development stage life of whole human aging stage reproductive stage maturation stage growth stage P
  • 46. How to understand the aging stage • Aging not part of the life plan for multicellular organisms like us • aging is a disease; it is a deviation (or set of deviations) from this life plan, which can in principle be rectified by treatment or engineering (SENS) – thus it is not a stage at all • aging is a post-reproductive pseudo-stage: (some) organisms manage to survive after the (last genuine) stage where they can reproduce; to be alive in this pseudo-stage is a lucky accidentc • Aging is part of the life plan; it is a genuine stage in the life of the organism, a reflection of its evolutionary program, and thus it must be in some sense adaptive • what is programmed for by the genome cannot be a disease • characteristic disease-like correlates of aging are not diseases 47
  • 47. How to deal with the Boorsean problems raised by ‘typical diseases of old age’ (benign prostatic hypertrophy)? • old Boorse: they are not diseases because they are statistically typical for the age group formed by aged people (they are like menopause …) • new Boorse: they are diseases, because typicality is to be determined by the reference class formed by healthy young adults this seems ad hoc See C. Boorse, “Replies to recent critics”, August 2012 48
  • 48. Boorse (Replies to critics) – it is not ad hoc: “biologists, though they catalogue immature stages, do not usually catalogue stages of senescence” 49
  • 49. old Boorse • A disease [later, pathological condition] is a type of internal state which impairs health, i.e., reduces one or more functional abilities below typical efficiency in a way that is detrimental to their individual survival [or] reproduction 50
  • 50. new (pseudo-)Boorse • A disease [later, pathological condition] in the aged is a type of internal state which impairs health, i.e., reduces one or more functional abilities below typical efficiency for young adults in a way that is detrimental to their individual survival [or] reproduction • “All functional declines with age to far below the young-adult mean would be pathological. “ • So menopause is a disease 51