**[Note: this XPrize idea follows mainly from the ‘Future of Longevity Impact Roadmap’ Grand Challenge #3 (e.g., Gaps 2 and 3: ‘No accurate models to experiment on’, and, ‘Unclear definition of Aging’), Breakthrough #8 (Aging Understood: A Robust Theory of Aging), and, Grand Challenge #1 (a ‘limited understanding of complexity’); as is the nature of such listings on a complex issue, the main topic here will overlap with several of the Gaps listed for the other Grand Challenges; the same is true for the various sub-components of the noted Breakthrough.]
“Thou hast nor youth nor age
But as it were an after dinner sleep
Dreaming of both.”
― William Shakespeare, Measure for Measure
Shakespeare (in the preceding quote) posited our perception/experience of both youth and (old) age as the product of a well-fed (or food-induced) dream. While partly still apt – certainly good nutrition is essential to health, and now we know that caloric restriction is somehow related to longer life/health span (in mice and worms anyways) – the Bard’s poetic definition is decidedly in need of an update.
Rationale For a Better Definition of Aging** **
As noted in the **Future of Longevity Impact RoadmapGrand%20Challenge%20#3,%20page%2020," title="Expediting Drug Development and Approval Process… We currently have an ‘unclear definition of Aging’, or perhaps, a clear definition of Aging is just starting to emerge. Although this bullet point comes after gap # 2 ('No animal* models to experiment on, I would argue that it should precede the latter gap insofar as developing a “concordant” animal model of Aging (or an anti-aging drug derived from it) must begin with a *useful and precise * definition of Aging (a hypothesis of sorts)… Otherwise we risk developing an ‘unfit’ animal mode and/or drug; any animal model developed from this working definition can then, in turn, be used to test the accuracy of our definition (and perhaps refine it) leading, ideally, to better research outcomes.
*Given the ethical issues surrounding certain types of scientific animal experimentation, and the recent advances in the science of *organoids3D%20collections%20of%20living%20cells%20from%20specific%20tissues%20grown%20on%20scaffolds%20and%20which%20mimic,%20in%20part,%20the%20patient-derived%20organ, the use of the term ‘animal model’ shall include these organoid models and any future improved versions of these, or, any new approaches to bio-medical model development.
This lack of clarity in our definition of Aging is probably due to two factors:
1] On-going but sporadic new research into Aging; what we call our scientific knowledge’ about Aging is in flux (i.e., always being updated, altered),
2] Generally, different takes or views on Aging (e.g., a gradual loss of physiological homeostasis, or, an accumulation of cellular/tissue damage, or, increasing genomic instability) from one researcher or team to another.
And, of course, the individual terms one chooses in constructing a working definition of Aging may themselves be ambiguous, not agreed upon, or both – but that is the reason for this proposed challenge!
Jumping ahead to Breakthrough #8 (page 32)… We recognize that ‘Aging Understood’ requires a ‘robust theory of Aging’. Such a robust theory (i.e., one able to explain a number of cases and tie together disparate research findings, such that accurate predictions can be made) – just like our animal model – will depend on the definition(s) we have constructed to guide us in our Aging research. Definitions and models are the building blocks of theories. In a perfect science world, a valid Theory of Aging would be built on optimal animal (or organoid) model experiments (which are bred or designed to be *representatives *of our definition). The definition we work with guides our theorizing and subsequent research paths (e.g., developing an experimental animal model, a slowed-aging drug, or a repeatable treatment, etc.) and thus sets the framework for what we can predict (i.e., constructing a predictive theory).
Finding Clarity: Formulating a ‘Definition of Aging’ XPrize
‘As complexity rises, meaningful statements lose their precision, precise statement lose their meaning.’ – Lofti Zadeh (inventor of ‘fuzzy logic’)
Going further: our ‘limited understanding of complexity’ (Grand Challenge #1; gap #4, page 17) is also reflective – to some significant extent – of the limitations of our theories which depend on their working definitions. Perhaps one day we will have a purely mathematical formula to describe and control the Aging process but until then, to deal realistically with complex systems (like a single brain cell), we must begin with clear and accurate words; we cannot allow our language to be inexact, imprecise, or unmeaningful. The purpose of a useful / precise definition is to *inject clarity into complexity * – NOT to increase complexity which would cause us to lose the precision and meaningfulness (according to Zadeh’s theorem) that we seek.
The XPrize ‘Definition of Aging’ Challenge:
How do we begin to construct a “working” definition of Aging – deriving its content from the best/current scientific research – such that it provides a CLEAR and useful (powerful) steppingstone to a robust theory, and/or a highly concordant animal model, and/or a better understanding of the complex process that is Aging?
What is your clearest and most useful definition of 'Aging? Why?
Explain how you chose your definition’s terms and why they are best, most accurate, or preferable to others. Cite all relevant research used in constructing your definition. If your definition of Aging is entirely or mostly novel (i.e., not derivative of prior research or other theories/models of of Aging), explain how it was arrived at (i.e., what is its source or inspiration, and, why is it preferable to existing or potential newer definitions) and why it would lead to a better experimental model, and/or Theory of Aging, and/or improve our understanding of biological complexity in the context of health and aging.
Your definition may be as expansive or extensive as you deem necessary (and probably should be).