Post on 21-Nov-2014
description
Ontology of Aging and DeathBarry Smith
http://ontology.buffalo.edu/smith
Presented at the Rostock Symposium on Systems Biology and Bioinformatics in Aging Research, September 20, 2013
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Aging has something to do with time
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applies to both time intervals and processes3
The Allen Interval Calculus
has something to do with death(we need both processes and process boundaries)
Beginning
Ending
Threshold / Meeting point
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for example: Aging and Death
Beginning
Ending
Threshold
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Aging
Death
When does aging begin?Beginning
Ending
Threshold
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Aging
Death
?
When does baldness begin?
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Aging
Death
Processes in the organism
Intervals of time
occupy
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Aging
Death
Process boundaries
Instants of time
occupy
Is death a process or a process boundary?
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Aging
Death
Processes in the Organism
Regions of Time
occupy
Dying
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death in the Gene Ontology
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is death 1. a biological process, or 2. the terminal boundary of a biological process?
A philosophico‐onto‐biological puzzle
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is death 1. a biological process, or 2. the terminal boundary of a biological process?
A philosophico‐bio‐gerontologicalpuzzle
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aging part_of life of organismdeath boundary_of life of organism
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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
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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 organismNOT: every instance of life of organism has_part aging
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because a life may be cut short by early deathThus also NOT: death boundary_of process of aging
death may not follow any process of agingNOT: 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
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How to define ‘life of organism’?Roughly: The sum total of all processes taking place within the spatiotemporal region occupied by the organism
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t1
t3t2
• 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?
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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)
VisceralPleura
Pleural Sac
Parietal Pleura
Anatomical Space
OrganCavity
Serous SacCavity
AnatomicalStructure
Organ
Serous Sac
MediastinalPleura
Tissue
Organ Part
Organ Subdivision
Organ Component
Organ CavitySubdivision
Serous SacCavity
Subdivision
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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
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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
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The Gene Ontologyrepresents 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 processesWhat 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 typeIt does not fit into the canonical cycle of stages
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“Reproductive stage” in Bioportal
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How do we represent an organism’s canonical life plan?
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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 profilesThere 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
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GO has a non‐unified treatment of stages (aka phases)
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but it mainly deals with stages through use of ‘developmental’
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developmental pigmentation is a special kind of pigmentationdevelopmental aging is a special (= normal) kind of aging
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GO:0043473 pigmentation
Definition:The deposition or aggregation of coloring matter in an organism, tissue or cell.
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developmental pigmentation
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developmental pigmentation
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pigmentation during development (≠ developmental pigmentation)*
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*although GO asserts the two as synonyms
Where can one find a good ontology of stages?
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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 arisessporophyte = 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 plantPO:0025337
PP
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whole plant development
stagePO:0007033
gametophyte development
stagePO:0028003
sporophyte development
stagePO:0028002
life of whole plant
PO:0025337
plant spore stage
PO:0025375
gametophyte vegetative stage
PO:0025340
gametophyte dormant stagePO:0025342
gametophyte reproductive
stagePO:0025341
gametophyte senescent stage
PO:0025343
sporophyte senescent
stagePO:0007017
sporophyte dormant stagePO:0007132
sporophyte reproductive
stagePO:0007130
sporophyte vegetative stage
PO:0007134
plant zygote stage
PO:0028002
PP
is_apart_
of
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Plant Stage Ontology (principal whole plant development stages)
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Life cycle of Selaginella apoda (Felsen Moosfarn)
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44http://blog.botanybill.info/?p=1225
sporophyte senescent stagePO:0007017
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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.
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GO:0007568: agingDefinition: 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).
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GO requires a term for developmental aging
Vascular plant life cycle
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http://www.flickr.com/photos/claytonvnps/8507360783/
http://www.flickr.com/photos/97311348@N07/9778785044/sizes/o/in/photostream/
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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
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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
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age-dependent behavioral declineGO: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.
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GO:0035982: age-dependent
behavioral decline
Summarizing: whole (human) organism stages in GO‐PO style
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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_apart_of
P
Acknowledgements
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Gene Ontology (GO)Jane Lomax (EBI)Chris Mungall (Berkeley)
iPlantRamona 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)