What is the philosophy of biological aging research/biogerontology/translational geroscience/? Introduction

So far on the course of Open Lifespan the fact that my number one professional occupation is being an active aging/longevity biologist (working at an aging/longevity startup) remained quite hidden, with a reason. While Open Lifespan is an attempt to formulate ethical, political, metaphysical and psychological questions and answers around our biomedically possible, upper limit healthy longevity trajectory, the following attempt below tries to investigate the science itself, the biological and medical (together: biomedical) problems of aging and longevity. 

I would introduce here the philosophy of biological aging research /biogerontology/translational geroscience as a new, expected sub-discipline within the broadly defined field of philosophy of biology trying to frame conceptual problems and work out solutions concerning our state-of-the-art understanding of biological aging and the interventions designed to counteract it. Please note that while I am aware of the difference between the terms ‘philosophy of biological aging’ and ‘philosophy of biological aging research’, by now I use these terms interchangeably.

This endeavour is a deeply interdisciplinary enterprise that can be built upon an up-to-date knowledge of the incredibly progressing fields of molecular and cellular biogerontology and translational geroscience (discipline #1) and then use the toolset of analytical philosophy (discipline #2) and the concepts of the philosophy of science (discipline #3, mainly as philosophy of biology particularly, but not exclusively), while informed by methods in computational biology/bioinformatics (discipline #4) and rapid advances in machine learning (discipline #5). Quick comment on ‘interdisciplinary’: it is ‘interdisciplinary’ in a sense of relying on existing feedback loops and corrections between the insights of the researchers in the different component disciplines, please see this good explanation on the term (and terms around) by Frances Drachenberg.   

These 5 disciplines can be considered as just 3 in an aggregated manner as philosophy of science and analytical philosophy are on the same argumentative platform and they can be considered continuous, overlapping fields (many consider mainstream philosophy of science as part of mainstream analytical philosophy in English-speaking countries) and computational biology/bioinformatics and machine learning are also heavily overlapping these days.

Let’s see the 5 components detailed a little bit:

First, the 3 majors:

Biological aging research/molecular and cellular biogerontology/translational geroscience

There’s finally an emerging scientific consensus about our understanding of the major molecular and cellular hallmark processes driving biological aging, while there has been ample older evidence for the age-associated disease risks with increasing chronological age. On the other hand there’s statistical evidence on the advancing front of old-age survival supporting the malleability of  biological aging. The new paradigm was introduced [not without previous precedence, think of the SENS ‘seven deadly sins’ damage list by Aubrey de Grey] in 2013 in Cell magazine by 5 well-known European aging researchers where they have mostly used the term aging research to describe this field. The  term ‘translational geroscience’ has been suggested first in 2014 by 2 US researchers, in the journal Aging in a paper entitled: Translational Geroscience: Emphasizing function to achieve optimal longevity. Authors introduce the new interdisciplinary approach as:

 ‘investigators with interests in the biological aspects of aging from model organisms to human epidemiology (population aging) must work together within an interactive process that we describe as translational geroscience.    An essential goal of this new investigational platform should be the optimization and preservation of physiological function throughout the lifespan, including integrative physical and cognitive function, which would serve to increase healthspan, compress morbidity and disability into a shorter period of late‐life, and help achieve optimal longevity. ‘

Translational Geroscience: Emphasizing function to achieve optimal longevity by Douglas R. Seals and Simon Melov

Interestingly this perspective piece was published after the Hallmarks paper was already out and making waves, and although does not reference it, certainly builds upon it as a big enabler in terms of designing interventions counteracting the biological aging process.

Philosophy of science as philosophy of biology

Historically philosophy of science was focusing on  math and physics for most part of the 20th century and those long decades left their traces on the field as a whole, with a lasting effect on the concepts used and questions asked. Some questions can obviously formulated meaningfully for all branches of formal and natural sciences, for instance what constitutes progress in a particular field, what are the basic methods that are considered valid and form the core toolset of discipline or what level of quantification is characteristic of the current stage.

The good news is that in the 21st century finally we have  a proper, stand-alone philosophy of biology emerging, emancipated from a forced reductionism and formalism wanting to ground everything that happens in the natural sciences in the realm of physics. Readers are recommended to read for a starter, Paul Griffiths’ (bit outdated as from 2008) take on current Philosophy of Biology in the Stanford Encyclopedia of Philosophy, from 2008 (time for an update I guess?). There he mentions 3 types of philosophical questions concerning biology.

The first type, already mentioned above, are questions inherited from the existing tradition of (mainly physics-focused) philosophy of science, reformulated in the context of biology. I don’t think that the systematic application of these questions and concepts are going be the most relevant right now concerning the rapidly developing state of aging research/biogerontology/translational geroscience, but certainly can be used and asked and might contribute to a further understanding for the acting life scientists too. In fact, am going to mention one such question in the examples later.

The second type are troubling conceptual questions arising from the particular biological research field itself. I think this is where the meat of the matter is going to be concentrated in the emerging field of philosophy of biological aging research. The amount of progress happening in aging research constitutes a number one demand to use philosophical tools to advance understanding and clear out the conceptual skies, so there’s sufficient visibility on muddy roads of actual science. If the bulk of philosophers of biology are thinking in a naturalistic framework arguing for a continuity between science and philosophy then asking internally motivated conceptual questions about biological aging is the way to go and provide further support for this framework.

Third, biological results, analogies can be applied to illuminate traditional philosophical questions. This leads out of the new field am talking about but maintains a connection to traditional problems of philosophy. Non-traditionally speaking, Open Lifespan philosophy is completely motivated by the counterfactual situation in which the successful  counteracting of biological aging process through biomedical means guarantee a much longer healthy lifespan. This leads, in a narrow sense of Open Lifespan, to political philosophy, ethical and metaphysical questions, nevertheless it has nothing to do strictly speaking, methodologically with how the questions can be discussed within the philosophy of translational geroscience. These are standalone and separate investigations even if they are united by the strong motivation to counteract biological aging processes. One can do philosophy of translational geroscience without committing itself to the relevance or desirability of an Open Lifespan scenario. On the other hand am publishing these posts here as in a broader sense and in my person this is a big continuum where the philosophy of longevity can be developed and my rare double-training and experience serves as a guarantee of serious investigation. More on this connection and separation later.

One great sign of continuity of the disciplines and interaction between biologists and philosophers of biology is that they increasingly publish in the same journals, for instance eLIFE has a great collection of articles in philosophy of biology showcasing the diversity and progress in the field, published in 2019, edited by Helga Groll.

Also PNAS published recently an opinion piece on Why science needs philosophy by a coalition of philosophers and scientists (first author is Lucie Laplane), focusing mainly on good examples on how the philosophy of biology can contribute to resolving the conceptual problems of biologists. It is sort of a must read entry to the field.  

In terms of the different subfields within the philosophy of biology eg. philosophy of molecular biology, developmental biology, immunology, bioinformatics it is likely that considering the notoriously broad-spectra nature of biological aging, the majority of these subfields might lend some additional insights to the philosophy of biological aging (research).

Analytical philosophy

This is mainly a methodological point here, the use of the well worked out argumentative tool set involving heavy use of logical reconstruction of arguments using intensional and modal logic, the counterfactual methodology of thought experiments. One example worth mentioning is by the aforementioned Lucie Laplane and Eric Solary on a classification of stem cells. They have ingeniously used well worked out philosophical property concepts like categorical, dispositional, relational to look for the definition of ‘stemness’and articulate conceptual problems with it. As somebody who has started out as a mitochondrial and stem cell biologist and worked with so called mesenchymal stem cells from the bone marrow (at Tulane University in New Orleans amongst others), I can certainly appreciate these efforts. The semantic/conceptual mess around MSCs is so big that some called for dropping the term altogether from the vocabulary of stem cell biologists.

The 2 minor, supporting disciplines

I’m not going to over-emphasise these here, but keep them on the shelf by now (so when they enter the discussion it’ll be a thing).

computational biology/bioinformatics

Present-day biology is as data-heavy as it gets. I can attest to this first-hand as for 9 years between 2010 and 2019 I’ve been working as a bioinformatician and head of the data curator team at the biggest mass spec proteomics database of the world, at the PRIDE Team at the EMBL-EBI. I’ve started with datasets on average 50 GB of size and numbered in the hundreds and throughout the 9 years we have experienced exponential growth routinely handling dataset of several TBs and 10 000, instead of a couple of hundred. At the same time,  the level of complexity of these mass spec proteomics datasets also increased several fold, am thinking about a largely qualitative reporting of peptide and proteins turned into fully quantitative reporting of relative abundances, MS1 and 2 intensities and lot more PTMs have been added as a new dimension, and the search space of mass spectra have been combinatorially blown up. The philosophy of bioinformatics and computational biology is also an emerging field, let just mention Philosophy of Biology: The challenges of big data biology by Sabina Leonelli, published in the aforementioned eLIFE collection.

machine learning

Another field that needs no detailed introduction here as a growingly essential toolset of making sense of biological patterns in the data-heav(enl)y state of current biological research. In fact, I don’t even talk about it more here (just when a particular problem is discussed), or use it by another name to avoid hype.

After all this ‘administration’, let’s substantiate the philosophy of aging research by mentioning several different types of questions and problems that I deem to be crucial for this emerging field. I’ve covered 2 of them during my recent longer talk at Eotvos University Logic/Philosophy of Science seminar in Budapest (slides will come soon, hopefully). However, I took a lot of your time already and it makes sense to dedicate a separate, follow-up post to this. Stay tuned!