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Ontology of Aging and 
Death
Barry Smith
http://ontology.buffalo.edu/smith
Presented at the Rostock Symposium on Systems Biology and 
Bioinformatics in Aging Research, September 20, 2013
1
Aging has something to do with 
time
2
applies to both time intervals and processes
3
The Allen Interval Calculus
has something to do with death
(we need both processes and process boundaries)
Beginning
Ending
Threshold / Meeting point
4
for example: Aging and Death
Beginning
Ending
Threshold
5
Aging
Death
When does aging begin?
Beginning
Ending
Threshold
6
Aging
Death
?
When does baldness begin?
7
8
Aging
Death
Processes in 
the organism
Intervals of time
occupy
9
Aging
Death
Process 
boundaries
Instants of time
occupy
Is death a process or a process boundary?
10
Aging
Death
Processes in 
the Organism
Regions of 
Time
occupy
Dying
11
death in the Gene Ontology
12
is death 1. a biological process, or 2. the terminal 
boundary of a biological process?
A philosophico‐onto‐biological 
puzzle
13
is death 1. a biological process, or 2. the terminal 
boundary of a biological process?
A philosophico‐bio‐gerontological
puzzle
14
aging part_of life of organism
death boundary_of life of organism
15
Aging
Death
Life of the 
Organism
Regions of 
Time
Conception …
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
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
How to define 
‘life of organism’?
Roughly: The sum total of all processes taking place 
within the spatiotemporal region occupied by the 
organism
18
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
• 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
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
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
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
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
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
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
“Reproductive stage” in Bioportal
27
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
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
GO has a non‐unified treatment 
of stages (aka phases)
30
but it mainly deals with stages 
through use of ‘developmental’
31
developmental pigmentation is a special kind of 
pigmentation
developmental aging is a special (= normal) kind of aging
32
33
GO:0043473 pigmentation
Definition:
The deposition or aggregation of coloring matter in an
organism, tissue or cell.
34
developmental pigmentation
35
developmental pigmentation
36
pigmentation during development (≠ 
developmental pigmentation)*
37
*although GO 
asserts the two as 
synonyms
Where can one find a good 
ontology of stages?
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
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
Life cycle of Selaginella apoda (Felsen Moosfarn)
42
http://www.youtube.com/watch?v=BTXkh34BmZs
43
44http://blog.botanybill.info/?p=1225
sporophyte senescent stage
PO:0007017
45
46
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
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
Vascular plant life cycle
49
50
51
52
http://www.flickr.com/photos/claytonvnps/8507360783/
http://www.flickr.com/photos/97311348@N07/9778785044/sizes/o/in/photostream/
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
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
56
57
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
GO:0035982: 
age-dependent
behavioral decline
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
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)

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