Aging is agings: towards a recursive definition of biological aging(s); part 2, Explication

In the first part of this study, Aging is agings: towards a recursive definition of biological aging(s); part 1, definition the following definition of biological aging(s) was introduced:

Biological aging is agings underneath, the result of multiple, diverse, separate but malleable processes, eventually compromising normal functions of the organism at different rates and at all levels.

Today it is explication time to build up the argument behind this definition. I have 4 points to offer today in the forms of questions and brief descriptive hints in the titles, here they are.

#1 What is the most confusing thing about biological aging? It’s diversity, plurality and broad-spectrum

#2 Why we need to come up with a good working definition of biological aging? Because current status looks like a prescientific and confusing mess

#3 Why we must come up with a good consensus definition? To acknowledge and further the emerging consensus framework within aging research

#4 What kind of definition we would like to come up with? An explicative one, both stipulative and descriptive, innovative and conservative at the same time

Let’s see the meat of the matter.

#1 What is the most confusing thing about biological aging? It’s diversity, plurality and broad-spectrum

Let’s acknowledge, that the failed attempts to define biological aging properly are mainly due to the hydra-like nature of this phenomenon, namely that it seems to involve most biological, physiological processes, and a plethora of different kind of molecular and cellular damages.

When I was looking into the state of biological aging theories in the nineties as an undergrad student I found and read the following paper by Medvedev that lists as many as 300+ theories of aging.

Medvedev ZA. An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc. 1990 Aug;65(3):375-98. Review. PubMed PMID: 2205304.

This inflated number tells us something about the state of aging research back then, for instance Medvedev lists literature data and ‘theories’ based on 1-2 studies/papers investigating specific processes like ‘Progressive demethylation of proteins’ and ‘Progressive deamination of glutaminyl and asparaginyl residues in proteins’ [1].

Medvedev himself highlight 2 reasons for the sorry state of affairs, please see highlighted section at the end of the abstract by me: i., no single cause ii., different and independent forms of senescence.

#2 Why we need to come up with a good working definition of biological aging? Because current status looks like a prescientific and confusing mess

Here’s a curious thing that anybody who has ever reviewed papers within aging research/biogerontology/geroscience might have experienced, and in case not yet, hereby I invite them to go out and do a search on PubMed or Europe PMC and check themselves.

For some reason almost all scientists feel compelled to come up with their own introductory definitions of aging, usually as the first sentence, or part of the first paragraph, of the introduction of the paper. Not too surprisingly these opinions on what aging is differ a lot. These ‘dictionary entries’ on aging many times find their way into he abstract itself. Another interesting feature is that many of these examples refer back to earlier attempts to establish a sort of ‘authority’ view on what aging is, but nevertheless ending up referring to other highly idiosyncratic definitions that were never accepted as consensus views within the research community.

It’s important to understand that the actual aging/longevity researchers cited below mostly represent top research (myself being one obvious exception, although I do interesting stuff too :)) but they usually (and this applies to most biogerontologists) don’t have the necessary philosophical background (again myself being an exception here :)) to realise a proper definition can be worked out or indeed to understand what can be gained from such a good working consensus definition. I believe this last task, to show the effectiveness and productivity of a good operational consensus definition, can be sufficiently hinted at in this current study too.

After making sure that my study cannot be used to offend researchers within the field, here are some recent examples – quite randomly, frankly – all from papers published this year and studied by me:

Example #1: Aging underlies progressive changes in organ functions and is the primary risk factor for a large number of human diseases refers to Derek Harman’s proposal actually, from 1991. Harman, D. The aging process: major risk factor for disease and death. Proc Natl Acad Sci U S A 88, 5360-5363 (1991). 

In: Lehallier et al: Undulating changes in human plasma proteome across lifespan are linked to disease

Example #2: Aging is characterized by a gradual degeneration of physiological capacity and the diminished ability to cope with environmental stresses, which in turn leads to a heightened susceptibility for age-related diseases referring to Kenyon CJ. The genetics of ageing. Nature. 2010 Mar 25;464(7288):504-12. doi: 10.1038/nature08980. Review. Erratum in: Nature. 2010 Sep 30;467(7315):622. PubMed PMID: 20336132.

In: Wen Bin Goh W, Thalappilly S, Thibault G. Moving beyond the current limits of data analysis in longevity and healthy lifespan studies. Drug Discov Today. 2019 Sep 6. pii: S1359-6446(19)30337-X. doi: 10.1016/j.drudis.2019.08.008. [Epub ahead of print] Review. PubMed PMID: 31499187.

Example #3: Aging is the progressive decline in functional integrity and homeostasis, culminating in death.

In: Singh PP, Demmitt BA, Nath RD, Brunet A. The Genetics of Aging: A Vertebrate Perspective. Cell. 2019 Mar 21;177(1):200-220. doi: 10.1016/j.cell.2019.02.038. Review. PubMed PMID: 30901541.

What is the take-away from these 3 examples?

We read about ‘progressive changes in organ functions’, ‘primary risk factors for human diseases’, ‘gradual degeneration of physiological capacity’, ‘diminished ability to cope with environmental stresses’, ‘progressive decline in functional integrity and homeostasis’ and we see several of these features overlapping and probably being replaceable with each other under some extra conditions but we see no effort to standardise this definition or acknowledging the lack of consensus definition.

 If this is not enough to show the diverse elements and different emphasises provided by different authors in an idiosyncratic manner then here’s 6 more below from earlier years starting with Peter Medawar in 1952. Please note the last one is the first version of the definition I’m proposing here, from 2017 [2].

Compare this with what’s going on with the deepening of our knowledge on the different versions of diabetes and a proposed new classification of it , suggesting acknowledging the heterogeneity of Diabetes Type 2 by turning it into 4 different subgroups.

#3 Why we must come up with a good consensus definition? To acknowledge and further the emerging consensus framework within aging research

As I wrote in What is the philosophy of biological aging research/biogerontology/translational geroscience/? Introduction

There’s finally an emerging scientific consensus about our understanding of the major molecular and cellular hallmark processes driving biological aging.

Curiously the 5 authors of the Hallmark framework had their own version of defining biological aging, please see the 4th definition in the figure above, but they are not realising that the proposed 9 hallmark processes might actually serve as a foundation for an actual consensus definition!

But we are at a point within aging research when there’s most of the elements are given that can be pulled into a consensus definition and it is a must for achieving some consolidation and long due conceptual clarity in the field. Imagine all the aging paper reviews to start by referencing this consensus definition and build up their arguments along the line of the particular component their study is relating to, instead of starting with idiosyncratic, journalistic like introduction (borderline op-ed pieces). In short, there’s a need and a must for a handbook definition to acknowledge, stabilise and develop further the existing consensus framework.

#4 What kind of definition we would like to come up with? An explicative one, both stipulative and descriptive, innovative and conservative at the same time

Formally and philosophically speaking there are many kinds of definitions we can consider when looking for one for biological aging, and I refer here to the Definitions entry by Anil Gupta in SEP, but what is worth considering here is what kind of definitions are out there that are used within science and what kind of definitions might be used within the biomedical sciences [3].

The type of definition we are looking for to capture biological aging scientifically are productive and innovative in a way triggering further questions and offering ways to answer them, and conservative in a way as to establish and stabilise already existing knowledge [4].

For instance for thousands of years cancer has already been known as a disease that kills people but that it is an uncontrolled division of abnormal cells as a mechanism behind was only established in the 20th century.

Going back now to productive mixed innovative/conservative definitions.

On the one hand we have so called descriptive definitions, these are conservative attempts to to fix already existing usage of the terms defined. On the other hand there are stipulative definitions claiming new grounds by generating meaning without the establishment of previous use.

Luckily we have so called explicative definitions, capturing the best of both worlds (of descriptive and stipulative def-s), a definition that ‘respects some central uses of a term but is stipulative on others’ according to Gupta [5].

My hypothesis is that most productive scientific and biomedical definitions are of the explicative kind, but am not going to substantiate this claim here further, only to show through the proposed definition of biological aging separate elements involved in the explicative definition.

But first let’s see what is meant exactly by the explication process involved here by introducing the theory and some examples of explication as it was proposed within the philosophy of science by Rudolf Carnap back in 1950, in the first chapter, called On Explication, of the book Logical foundations of probability [6].

According to Carnap, the process of explication is the transformation of an inexact prescientific concept, the explicandum, into an exact, scientific concept, the explicatum. 

The best worked out example used by Carnap is our common heat sensation related to warm things. Carnap shows 3 different kind of scientific explicatum-s that were introduced as an actual sequence transforming the original concept/content into a more scientific one at every step. Our common heat sensation was captured by the first explicatum, Warm, a classificatory concept, a property, followed by a comparative concept, Warmer, a dyadic relation. Since we are talking about concept-making in the natural sciences and we are talking about Carnap, the most scientific explication in this series is the quantitive one, Temperature, establishing our growing practical knowledge related to the higher discriminating power of the thermometer. A stipulative element here is that in an everyday situation and language we can think of a moderately heated room as Warm, but also as Cold depending on whether we have entered it from outside or after a hot shower. But the temperature of the room stays the same and the scientific concept overwrites (Carnap is using the term ‘overrule’) the prescientific heat assessment.    

Now let’s think about Aging and our mixed and super-complex common sense baggage related to it. We have the classificatory looking concept of Young and Old, used by most of us all the time to label people by just looking. In order to start to use the term Middle-aged we need to have a comparative concept that is able to order young, middle-aged and old, just like applying the concepts Younger and Older is a comparative operation. And we have our DOB related simple arithmetical, yet definitely quantitative concept of chronological age. Still we have not stated anything scientific about biological aging, yet in our definition of biological aging, somehow all of these concepts should be accounted for or overruled. Most importantly our concept of biological aging should not just catch correlation with chronological age but the disconnect from it as well, to explain accelerated or decelerated phenotypes too.

Carnap lists 4 criteria a good scientific explicatum should meet: 

i., similarity to the explicandum, 

ii., exactness to introduce the explicatum ‘into a well-connected system of scientific concepts’,

iii., fruitfulness to be useful in formulating empirical laws or logical theorems, I take this feature roughly the same as scientific ‘applicability’ or ‘productivity’ and

iv., simplicity as simple as possible and allowed by the above 3 criteria.

Before I can tell why and how my proposed definition of biological aging is an explicative one and how are these criteria, or the modified forms are met by this definition, we need to actually explain what makes it a formally correct recursive definition, which is the crucial insight of the proposition, in the next part of our study. Stay tuned!

Notes

[1] Another good and classical philosophy of science question that can be asked here is what can be called a scientific theory and what does the smallest amount of viable scientific theory in a particular discipline consist of?

[2] I published that table originally here, in 2017.

[3] Then we can also ask what kind of definitions might fit disease definitions. Would appreciate any work done by philosophers of medicine pointing towards this direction.

[4] Please note that we also use definitions as shorthands, for instance see PCM triangle example, and these definitions are for convenience’s sake, and obviously not something we are after in case of biological aging.

[5] Gupta is using the mathematical example of the definition of ordered pair in set theory for an explicative definition.

[6] Kant also had a method of Explication, please see some differences between the 2 kinds of Explication discussed in the context of philosophical methodology by Giovanni Boniolo in Kant’s Explication and Carnap’s Explication: The Redde Rationem.