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Ontology of aging and death


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The idea underlying biomedical ontology is that, if common terms are used to annotate or tag heterogeneous data collected by scientists working in different disciplines, then these data will be more easily reused for integration and
analysis. To this end, the terms in ontologies need to be carefully defined. Smith examines definitions
of terms central to ageing research in this light, focusing on the Gene Ontology (GO), the Foundational Model of Anatomy Ontology (FMA) and the Plant Ontology (PO).

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Ontology of aging and death

  1. 1. Ontology of Aging and  Death Barry Smith Presented at the Rostock Symposium on Systems Biology and  Bioinformatics in Aging Research, September 20, 2013 1
  2. 2. Aging has something to do with  time 2
  3. 3. applies to both time intervals and processes 3 The Allen Interval Calculus
  4. 4. has something to do with death (we need both processes and process boundaries) Beginning Ending Threshold / Meeting point 4
  5. 5. for example: Aging and Death Beginning Ending Threshold 5 Aging Death
  6. 6. When does aging begin? Beginning Ending Threshold 6 Aging Death ?
  7. 7. When does baldness begin? 7
  8. 8. 8 Aging Death Processes in  the organism Intervals of time occupy
  9. 9. 9 Aging Death Process  boundaries Instants of time occupy
  10. 10. Is death a process or a process boundary? 10 Aging Death Processes in  the Organism Regions of  Time occupy Dying
  11. 11. 11 death in the Gene Ontology
  12. 12. 12 is death 1. a biological process, or 2. the terminal  boundary of a biological process? A philosophico‐onto‐biological  puzzle
  13. 13. 13 is death 1. a biological process, or 2. the terminal  boundary of a biological process? A philosophico‐bio‐gerontological puzzle
  14. 14. 14
  15. 15. aging part_of life of organism death boundary_of life of organism 15 Aging Death Life of the  Organism Regions of  Time Conception …
  16. 16. death boundary_of life of organism every instance of death boundary_of life of some organism ? every life of an organism has_boundary some death  16 Metabolism Death Life and  afterlife of  organism Regions of  Time Abiotic chemistry
  17. 17. aging part_of life of organism every instance of aging part_of life of some organism NOT: every instance of life of organism has_part aging 17 because a life may be cut short by early death Thus also  NOT:  death boundary_of process of aging death may not follow any process of aging NOT:  aging has_boundary death  premature aging may be followed by a period of  rejuvenation
  18. 18. How to define  ‘life of organism’? Roughly: The sum total of all processes taking place  within the spatiotemporal region occupied by the  organism 18
  19. 19. How to define  ‘life of organism’? Roughly: The sum total of all processes taking place  within the spatiotemporal region occupied by the  organism 19 t1 t3 t2
  20. 20. • How to distinguish age-related causes (aging processes) from other causes of death? • Roughly: age-related causes = processes normally part of the normal aging process • What does ‘normally’ mean? 20
  21. 21. 21 has 83281 types and 3 million relations representing canonical adult human anatomy = the Bauplan generated by the coordinated expression of the organism’s own structural genes. Canonical anatomy contrasted with variant anatomy and with instantiated anatomy Canonical ≠ statistically normal Foundational Model of Anatomy Ontology
  22. 22. 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 22
  23. 23. canonically (normally) human  beings have 32 teeth • 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  23
  24. 24. 24 The GO is a canonical representation • “The Gene Ontology is a computational  representation of the ways in which gene products  normally function in the biological realm” • Nucleic Acids Research. 2006: 34. Thus the GO is distinguished from a disease ontology  and from an ontology of biological processes in vitro 
  25. 25. 25 The Gene Ontology represents what is normal in the realms of  • cellular components • molecular functions  • biological processes = roughly, what pertains to ‘wild type’, as  opposed to experimentally modified, organisms = what happens when genes, proteins function  normally in the development of an organism
  26. 26. What makes aging processes  normal aging processes What makes a case of premature aging non‐normal? What makes an early death early? Answer: that it does not fit in the right way into the  life plan for an organism of this type It does not fit into the canonical cycle of stages 26
  27. 27. “Reproductive stage” in Bioportal 27
  28. 28. How do we represent an organism’s canonical  life plan? 28 Aging processes Death Processes in  the organism Stages Regions of  time organism  senescence  stage organism  maturation  stage organism  reproductive  stage
  29. 29. What makes the ontology of  stages so hard? Stages are not simply segments of the life of the  organism. Not all processes occurring in the organism in  the organism reproductive stage are reproductive  processes. BFO: process profiles There is a progression of stages, but some stages may  overlap (e.g. senescent stage and reproductive stage) and not all stages require specific earlier stages in order  to exist. Most importantly, cells, organs and other organism parts  go through stages too 29
  30. 30. GO has a non‐unified treatment  of stages (aka phases) 30
  31. 31. but it mainly deals with stages  through use of ‘developmental’ 31
  32. 32. developmental pigmentation is a special kind of  pigmentation developmental aging is a special (= normal) kind of aging 32
  33. 33. 33
  34. 34. GO:0043473 pigmentation Definition: The deposition or aggregation of coloring matter in an organism, tissue or cell. 34
  35. 35. developmental pigmentation 35
  36. 36. developmental pigmentation 36
  37. 37. pigmentation during development (≠  developmental pigmentation)* 37 *although GO  asserts the two as  synonyms
  38. 38. Where can one find a good  ontology of stages? 38
  39. 39. 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
  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 40 Plant Stage Ontology (principal whole plant development stages)
  41. 41. 41
  42. 42. Life cycle of Selaginella apoda (Felsen Moosfarn) 42
  43. 43. 43
  44. 44. 44 sporophyte senescent stage PO:0007017
  45. 45. 45
  46. 46. 46
  47. 47. GO:0010259: multicellular organismal aging Definition: An aging process that has as participant a whole multicellular organism. Multicellular organism aging includes loss of functions such as resistance to disease, homeostasis, and fertility, as well as wear and tear. Multicellular organisms aging includes processes like cellular senescence and organ senescence, but is more inclusive. 47
  48. 48. GO:0007568: aging Definition: A developmental process that is a deterioration and loss of function over time. Aging includes loss of functions such as resistance to disease, homeostasis, and fertility, as well as wear and tear. Aging includes cellular senescence, but is more inclusive. May precede death (GO:0016265) and may succeed developmental maturation (GO:0021700). 48 GO requires a term for developmental aging
  49. 49. Vascular plant life cycle 49
  50. 50. 50
  51. 51. 51
  52. 52. 52
  53. 53. 53 honour of Dr. Leonard Hayflick, co-author with Paul Moorhead, of the first paper describing it in 1961. Cells can also be induced to senesce by certain toxins, irradiation, or the activation of certain oncogenes. In response to DNA damage (including shortened telomeres), cells either age or self-destruct (apoptosis, programmed cell death) if the damage cannot be easily repaired. In this 'cellular suicide', the death of one cell, or more, may benefit the organism as a whole. For example, in plants the death of the water- conducting xylem cells (tracheids and vessel elements) allows the cells to function more efficiently and so deliver water to the upper parts of a plant. The ones that do not self-destruct remain until destroyed by outside forces. Though they no longer replicate, senescent cells remain metabolically active and generally adopt phenotypes including flattened cell morphology, altered gene expression and secretion profiles (known as the senescence-associated secretory phenotype) and positive senescence
  54. 54. 54 The End: Senescence and Cell Death (With Yuan Zhong and Jared Taylor) - Plants, like animals, employ cell death as a normal and necessary part of life. Cell death occurs during developmental processes, including embryo and leaf development, vascular tissue development, and various reproductive processes. Pathogen infection can initiate the hypersensitive response which can include a rapid cell
  55. 55. 55
  56. 56. 56
  57. 57. 57
  58. 58. 58 age-dependent behavioral decline GO:0035982 synonym (exact): behavioral aging Definition: A developmental process that arises as an organism progresses toward the end of its lifespan that results in a decline in behavioral activities such as locomotory behavior, and learning or memory.
  59. 59. 59 GO:0035982:  age-dependent behavioral decline
  60. 60. Summarizing: whole (human)  organism stages in GO‐PO style 60 whole human development  stage post‐natal development  stage life of whole human senescent  (aging) stage age‐dependent  behavioral decline stage reproductive  stage maturation stage growth stage P is_a part_of P
  61. 61. Acknowledgements 61 Gene Ontology (GO) Jane Lomax (EBI) Chris Mungall (Berkeley) iPlant Ramona Walls (University of Arizona) Plant Ontology (PO) Pankaj Jaswal, Laurel Cooper, Justin Elser (Oregon State University) Dennis W. Stevenson, Ciaran Maloney (New York Botanical Gardens) Ontology for General Medical Sciences (OGMS) Werner Ceusters (Buffalo) Lindsay Cowell (Texas) Albert Goldfain (Syracuse) Alan Ruttenberg (Buffalo) Richard Scheuermann (J. Craig Venter Institute)