The rabbit hole of temporal causation and biological aging

This is part 2 of my series on causation and aging. Last time I introduced the ladder of causation in aging where the bottom step of the ladder was also the most mysterious one that seems to be so intimately linked with all things aging that many people cannot think further: time. Our guiding questions were: How can time play a causal role in bringing about different forms of aging, and in our case, more specifically: can time be factored in as a cause in any conceptual or empirical sense of the diverse processes of biological aging? Here’s the edited slide I presented on this during my PhD seminar talk in Budapest. 

First of all, let’s note that the literature of biological aging research can provide several examples where the linguistic expression used to describe time’s connection to biological aging is suggestive of causality. For instance, Levine et al starts their paper as

Chronological time has been shown to elicit predictable hypo- and hyper-methylation changes at many regions across the genome, and as a result, the first generation of DNAm based biomarkers of aging were developed to predict chronological age.

An epigenetic biomarker of aging for lifespan and healthspan

The term ‘elicit’ is a phrase that can be interpreted as X (chronological time) triggering Y (DNA methylation changes). In the language of necessary and sufficient conditions – a complicated but important language as we will see later – triggering means chronological time being sufficient to cause methylation changes. Please also note that the sentence mentions ‘chronological time’, not the change of chronological time being able to elicit the change of methylation patterns on the DNA. 

This ‘triggering‘ phrasing leads us to the benevolent formulation of our first problem.

Problem #1. Let’s assume that somehow time itself is causing biological aging. Even if this were the case, what kind of explanation would this give us in order to understand biological aging more and design interventions against it? The problem is that it’s hard to think of an actual mechanism in which ‘chronological time’ kicks off biological aging. On the cause/trigger side we have ‘chronological time’, that is pretty much a very abstract concept for a biomedical researcher to think with, while on the other side we have the actual molecular and cellular mechanisms we are quite well acquainted with.   

Second, please note that this most mysterious bottom step of the ladder of causation in aging, is traditionally the domain of the ‘default’, ‘most foundational’, ‘almost complete’ natural science, physics. Can biomedical researchers working on aging research consult physics on this problem successfully? 

Here I formulate another problem.

Problem #2: There’s no dominant temporal theory of time in current physics that can be successfully applied in the context of biological aging that would link time to the onset or changes in biological aging.

There’s 3 theses can be made here, a weaker, a stronger and an even stronger one. The weaker one says that there has been no known (by me at least) successful attempt using physical theories of time in the context of biomedical aging research. This is a factual statement that can be refuted empirically by showing such an example under an agreed upon version of ‘successful’. 

The stronger one is a modal statement saying no existing theories of time in current physics can be successfully applied in this context. And there’s the even stronger one, saying that whatever physics knows about time, it is useless in the context of biological aging and designing clinical interventions to delay or stop it. Am not going to argue for these positions here, only formulate the problem with the intermediate, modal thesis in mind. Also I try to phrase this as a challenge in the hope that it triggers answers on part of actual physicists, still holding some version of reductionism within the natural sciences. More than happy to admit, that as a biologist I lack the necessary skills and knowledge to formulate my problems concerning biological aging and healthy longevity interventions with the help of physics.

In terms of contemporary physical thinking on time I’ve read recently The Order of Time by Carlo Rovelli, the famed quantum loop theorist. It is a popularising account on modern physics’ handling and understanding of time and temporal relations but it does develop its arguments in a philosophically interesting way. What we can learn about time is not too re-assuring though when it comes too linking it up to biomolecular, cellular or organismal level understanding of biological aging. It seems that Rovelli ‘dethrones’ time – he’s using the terms King Time & Father Time (p85-6) whose ordering of the world is not needed anymore by the world – from most of the relevant roles it could play higher up in the system. Already the names of the chapters of Part One of this book, called The Crumbling of Time, are indicative of the many losses the physical concept of time has suffered throughout the development of 20th century physics, the loss of unity, direction, independence …expressing how the concept of global time and global present became inconsistent, how the direction of time is an illusion and how time has been removed from all the relevant equations handlinh physical reality as a variable amongst others.

Eliminating the time parameter from the (largely partial differential) equations of a physical theory might actually become one sort of, ill-advised or not, methodological, albeit negative answer on what to do with the chronological age parameter when modelling biological aging. Get rid of it. Turn chronological age from an input, independent variable, to an outcome, dependent variable in biological aging research.

Half-joking aside, also slightly off the point, biological aging research has still a lot to learn from physical methods, statistical or simulations, but perhaps, not when it comes to handling the time parameter.

Another potential source of physics consultancy in biomedical aging and health might be quantum biology, see picture of one popularising book by legit scientists on the topic on the figure above. Now I remember quite well what my biology MS thesis supervisor told me back in the nineties about the potential fruits of quantum biology. He told me that quantum biochemistry was a hip idea in the 60s but somehow solving the Schrodinger equation to more than a couple hundred caesium atoms is till a no-go. Now am going to do an update on this, but the current situation prompts me to occupy a sceptical position about the usefulness of quantum biology in the short term. Just don’t expect to see it starting popping up as a reference point at the clinics.  

Perhaps by now it’s understandable why I’m talking about the rabbit hole of temporal causation, it is a hard problem for physics, that might try to solve it by eliminating time at all giving a negative answer for its applicability in healthy longevity interventions and this hole deepens when we look into conceptual attempts made in philosophy to make space for temporal causation. Will add a section on the latter, well later.