senescence and aging in GO

[gocentral]

The POC has been working on its terms for senescent stages, and we would like to request changes to the definitions of a several GO terms, in order to make them work better for plants.

GO currently has the following hierarchy:

aging >cell aging >>cellular senescence >multicellular organismal aging >organ senescence >>leaf senescence

Also, there is a term for ripening (GO:0009835), is_a anatomical structure maturation, but it should be a subtype of aging, with the synonym fruit senescence (see more details below).

Suggested changes:

aging (GO:0007568) Current definition: The inherent decline over time, from the optimal fertility and viability of early maturity, that may precede death and may be preceded by other indications, such as sterility.

Proposed definition: A developmental process that is a deterioration and loss of function over time. Comment: 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).

Note: There are many processes that are a deterioration and loss of function over time, but not all of them are aging. However, aging is a subtype of GO:biological process,which states that it is "pertinent to the functioning of integrated living units: cells, tissues, organs, and organisms", and GO:developmental process, which states that it is a "progression of an integrated living unit... over time from an initial condition to a later condition". These inherited properties make the definition of aging more specific.

At the POC, we felt that comment about sterility should probably come out, because sterility is a sign of aging, not something that precedes it, and the comment already says that aging may include a loss of fertility. GO has a term for aging-dependend sterility, a synonym of chromatin silencing at silent mating-type cassette, which is consistent with this.

We also had some discussion of the difference between aging and getting older. I think that "getting older" is more general than aging. Getting older occurs throughout an organism's or cell's entire life, while aging only occurs near the end of one's life, generally (but not always) after maturity. For example, a 6 year old child is getting older, that is, maturing, but is not aging, although some of his/her parts may be aging. Getting older could be a type of synonym for development.

cell aging (GO:0007569)

Current definition: Progression of the cell from its inception to the end of its lifespan. Source: GOC:jh, PMID:12044934

Proposed definition: An aging process that has as participant a cell after a cell has stopped dividing. Comment: Cell aging may occur when a cell has temporarily stopped dividing through cell cycle arrest (GO:0007050) or when a cell has permanently stopped dividing, in which case it is undergoing cellular senescence (GO:0090398). May precede cell death (GO:0008219) and succeed cell maturation (GO:0048469).

Note: The current definition is not consistent with the plant literature on cell aging. Also, the concepts of an inception and lifespan of a cell are a little vague. Does a cell's lifespan end when it divides? Not all cells age before they divide. See my comment above about the different between aging and getting older.

cellular senescence (GO:0090398)

Current definition: A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest. Source: GOC:BHF

proposed definition: A cellular aging process in which a cell permanently loses the ability to participate in the cell cycle (GO:0007049).

Comment: Cellular senescence may be accompanied by other cell aging processes, such as wear and tear or the dismantling of cellular components. Cellular senescence be a response to cellular stress or other stimuli, whereby normal cells lose the ability to divide through irreversible cell cycle arrest (post-mitotic senescence or stress-induced premature senescence, GO:0090400), or it may be intrinsic, in cells that have a finite capacity for division (mitotic senescence or replicative senescence, GO:0090399).

Note: The current definition is problematic, because it defines senescence only as stress-induced, but there is also intrinsic cellular senescence. This is supported by the different subtypes of cellular senescence that have been added to GO (see https://sourceforge.net/tracker/index.php?func=detail&aid=3026338&group\_id=36855&atid=440764).

I would ask that you add the following synonyms: mitotic cellular senescence as a synonym of stress-induced premature senescence (GO:0090400) post-mitotic cellular senescence as a synonym of replicative senescence (GO:0090399)

Also note that the definitions of cell cycle arrest (GO:0007050) is quite general, and could be construed to include cellular senescence. Perhaps it should be clarified with a comment that cell cycle arrest can include temporary suspension of the cell cycle, unlike cellular senescence that is permanent. Perhaps the term cell cycle arrest should only be used for temporary arrest of the cell cycle, reserving senescence for permanent arrest.

multicellular organismal aging (GO:0010259)

Current definition: The inherent decline of a multicellular organism over time, from the optimal fertility and viability of early maturity, that may precede death and may be preceded by other indications, such as sterility. Source: GOC:dph, GOC:isa_complete, GOC:mtg_sensu, GOC:sm

Proposed definition: An aging process that has as participant a whole multicellular organism. Comment: 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. May precede death (GO:0016265) of an organism and may succeed developmental maturation (GO:0021700).

As with aging, we felt that comment about sterility should come out, because sterility is a sign of aging, not something that precedes it.

Please add the following synonym: multicellular organism senescence (exact), monocarpic senescence (narrow)

organ senescence (GO:0010260)

Current definition: The process that occurs in an organ near the end of its active life that is associated with the dismantling of cell components and membranes, and an overall decline in metabolism. An example of this process is found in Arabidopsis thaliana. Source: GOC:mtg_sensu, GOC:sm

Proposed definition: An aging process that has as participant an organ. Comment: Includes processes such as cellular senescence (GO:0090398) and an overall decline in metabolism (GO:0008152). May succeed organ maturation (GO:0048799) and precede the death of the organ. Occurs in plant organs such as leaves or petals.

I don't know if there is organ senescence in animals.

leaf senescence (GO:0010150)

Current definition: The process that occurs in a leaf near the end of its active life that is associated with the dismantling of cell components and membranes, loss of functional chloroplasts, and an overall decline in metabolism. Source: ISBN:0387987819

Proposed definition: An organ senescence that has as participant a leaf. Comment: Has as participant a leaf (PO:0025034), or, more specifically, a vascular leaf (PO:0009025) or non-vascular leaf (PO:0025075). May succeed maturation and precede death of the leaf. Includes processes such as cellular senescence (GO:0090398) and an overall decline in metabolism (GO:0008152).

Note: Because of the all-some nature of the has_paricipant relation, the GO definition has to say leaf senescence has_participant leaf, but in every individual instance, the relation would be to vascular leaf or non-vascular leaf.

ripening (GO:0009835)

GO has the term ripening, which we suggest renaming "fruit ripening". Ripening is_a anatomical structure maturation, but it should be a subtype of aging, with the synonym "fruit senescence".

Current definition: The series of events causing changes in one or more characteristics of a fruit (color, aroma, flavor, texture, hardness, cell wall structure) to make it more attractive to animals and/or aid in seed dispersal.

Proposed definition: An aging process that has as participant a fruit. Comment: Ripening causes changes in one or more characteristics of a fruit (color, aroma, flavor, texture, hardness, cell wall structure) and may make it more attractive to animals and aid in seed dispersal.

synonym: fruit senescence

This term already has a taxon restriction on parent (for Angiospermae, presumably).

flower senescence (new term)

Note that there is an open tracker for flower senescence (https://sourceforge.net/tracker/index.php?func=detail&aid=3425355&group\_id=36855&atid=440764). I agree that we should add the term, but it is not a type of organ senescence, because a flower is not a plant organ. I will add a comment to that tracker.

All of the above definitions and synonyms could use POC:curators and Gan, 2010, in Senescence Processes in Plants (Annual Plant Reviews), ISBN:9781405139847 as reference.

I have written the definitions in the format the PO uses, with terse definitions and lots of information in the comment. However, if you prefer to put the information from the comments into the definition, that is okay.

Thanks for your consideration. The POC and I welcome discussion on these definitions from the GO curators.

Reported by: rlwalls2008

Original Ticket: geneontology/ontology-requests/9075

[gocentral]

Since aging is a developmental process, organ senescence should also be is_a organ development (GO:0048513) and leaf senescence should also be is_a leaf development (GO:0048366).

If GO were to set up organ development process as an XP of developmental process and has participant organ, then the second is_a parent could be inferred (same for leaf or flower).

Original comment by: rlwalls2008

[gocentral]

At the POC meeting on 1-3-12, we had some additional discussion of cell aging.

The definition needs to say "has principle participant", instead of "has participant". You could have a whole organism that has as participant a cell that is aging, but the whole organism is not going through a cell aging process. Thus, the cell has to be the principle participant.

The clause "after a cell has stopped dividing" should be from the definition, because the comment covers it. Also, we are not sure that aging only occurs when the cell stops dividing. Maybe a cell ages every time it divides, because that is when damage to the telomeres occurs.

A note about the proposed comment "Cell aging may occur when a cell has temporarily stopped dividing through cell cycle arrest (GO:0007050)": Cells can age during very brief periods when they are not dividing, between each division, no matter how short that period is.

It would be great if someone who was actually an expert on cell aging and cell senescence could chip in on this discussion! My proposed definitions are based on what I read in books and a few papers, not on any actual experience.

Original comment by: rlwalls2008

[gocentral]

See also, related SF item: https://sourceforge.net/tracker/?func=detail&aid=3425355&group\_id=36855&atid=440764

Original comment by: rebeccafoulger

[gocentral]

Hi Tanya,

We see you added alot of the previous senesence terms in, so we've assigned this one to you... yell if you object!

thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

• assigned_to: nobody --> tairtb

Original comment by: rebeccafoulger

[gocentral]

I'll have time to think and work on this issue next week.

Tanya

Original comment by: tberardini

[gocentral]

Lots of stuff to tackle here. Let's start with the easy things.

Agree on adding the following:

organ development --[i] organ senescence

leaf development --[i] leaf senescence

floral organ development --[i] floral organ senescence

Agree on renaming 'ripening' to 'fruit ripening'.

Agree on need for improvement of definition of cell aging (GO:0007569). The old one is to vague and could easily be confused with cell development, cell maturation or cell differentiation or all of those!

Original comment by: tberardini

[gocentral]

Re: fruit ripening/maturation/senescence

I think your suggestions are fine.

One thing that I think is happening is that in plants, fruit maturation and fruit senescence are synonymous. Please correct me if I'm wrong. That being the case, it makes sense to have fruit maturation/fruit ripening/fruit senescence as a child of aging. However, in other systems, maturation processes are most definitely NOT considered aging, whereas senescence is considered aging. I think that as long as we don't put anatomical structure maturation under aging, everything will still work out well.

Original comment by: tberardini

[gocentral]

Re: cellular senescence

All the kids of this term are stress-related. What you are thinking of as intrinsic cellular senescence is, I think, represented by the term 'chronological cell aging' which is a sibling of 'cellular senescence'.

Could you please provide sources for the synonyms suggested?

mitotic cellular senescence as a synonym of stress-induced premature senescence (GO:0090400) post-mitotic cellular senescence as a synonym of replicative senescence (GO:0090399)

Original comment by: tberardini

[gocentral]

I think that covers most of the issues. I don't have a problem with removing the references to sterility from the definitions of 'aging' and 'multicellular organismal aging'.

Original comment by: tberardini

[gocentral]

Thanks for looking into these, Tanya.

Re. fruit ripening: Although it makes more sense to me to say that fruit maturation is what happens up until senescence (ripening) begins, I agree that ripening and maturation are used synonymously by most people (and even in the PO). Therefore, I agree that it makes sense to have fruit maturation/fruit ripening/fruit senescence as a child of aging.

Re. cellular senescence: The references I have for these terms are on my desk in the city, so I will post more on this tomorrow.

Original comment by: rlwalls2008

[gocentral]

Most changes done. Still need to add synonyms with references.

Original comment by: tberardini

[gocentral]

Re. cellular senescence: I agree that chronological cell aging (GO:0001300, "The process associated with progression of the cell from its inception to the end of its lifespan that occurs when the cell is in a non-dividing, or quiescent, state.") could cover intrinsic cellular senescence, but I think it is more broad than that. It seems like chronological cell aging could also be a parent to replicative senescence, which I think of as a type of intrinsic senescence.

I am still not sure that cellular senescence should be defined only in terms of being stress induced. For example, I don't think replicative senescence (GO:0090399 'A cellular senescence process associated with the dismantling of a cell as a response to telomere shortening and/or cellular aging."), which is a subtype of cellular senescence, is induced by stress (see, for example, PMID:9282108: "The biology of replicative senescence" or http://en.wikipedia.org/wiki/Senescence), although I suppose one could argue that dna breakage and telomere shortening were a type of stress. I think of stress as something that is induced by external factors, but maybe that is not how the GO defines it.

Anyway, as I said, I am not an expert on cellular senescence, so I can go along with whatever the GO community decides. It was just that the definitions seemed inconsistent with my reading of the literature, not that there is a problem for using them the PO at this point.

Re. the synonyms: I just re-read the source ( Gan, 2010, first chapter in "Senescence Processes in Plants", Annual Plant Reviews, ISBN:9781405139847), and I think I mixed up the synonyms in my original comment. In fact, it turns out to be more complicated that I originally thought, so the synonyms don't really match up so well with the current GO terms. I would suggest that you not add the synonyms at this point. When someone who is really an expert in senescence decides they want to annotate plant genes for different types of plant cellular senescence, they can contribute new terms or synonyms as needed.

Original comment by: rlwalls2008

[gocentral]

OK. After doing some more reading myself, I've decided to take 'replicative senescence' up one level and make it a direct child of 'cell aging' and a sibling of 'cellular senescence'. This will be in keeping with the definition which mentions telomere shortening and cell aging - with no specific mention of stress. If we decide to review this entire slice of the ontology with the help of a cell aging expert, the term can be placed further down in the tree, if appropriate.

Will not add synonyms right now.

With that, I will close this issue.

Original comment by: tberardini

[gocentral]

• status: open --> closed-accepted

Original comment by: tberardini

[gocentral]

• Group: TAIR --> Plant Ontology

Original comment by: cooperl09