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?

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