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Metformin and Brain Aging

Nature news has an interesting piece on this study which examined the impact of metformin on the brain aging of monkeys. Encouraging findings. 

A sample from the news item:

A low-cost diabetes drug slows ageing in male monkeys and is particularly effective at delaying the effects of ageing on the brain, finds a small study that tracked the animals for more than three years1. The results raise the possibility that the widely used medication, metformin, could one day be used to postpone ageing in humans.

Monkeys that received metformin daily showed slower age-associated brain decline than did those not given the drug. Furthermore, their neuronal activity resembled that of monkeys about six years younger (equivalent to around 18 human years) and the animals had enhanced cognition and preserved liver function.

Cheers, 

Colin 

New Book!

 

Feels great to hold the finished product!

Cheers, 

Colin

The Genetics of Reproductive Longevity

Nature news has this interesting piece on two studies on the age of onset of menopause.  Some (rare) genes are implicated in premature menopause.  A sample:

One factor that could trigger that early menopause is the accumulation of DNA mutations in a person’s eggs. Such mutations can trigger the repair of the eggs’ DNA — or they can cause the eggs to self-destruct. The eggs’ response to DNA damage is key in determining egg number, says Murray. “And it’s egg number that determines your reproductive lifespan.”

Mutations can also increase cancer risk, and variants in four of the genes that the team uncovered were linked not only to early menopause but also to a higher risk of cancer.

...The team found that women who carried common DNA variants that previous research had associated with earlier age at menopause were more likely to pass mutations that had arisen in their eggs to their offspring.

The two studies mentioned in the news piece are here and here.

Cheers, 

Colin

Science Piece on the ITP

For 22 years the NIA’s “Interventions Testing Program“ has been assessing the potential for drugs to slow biological aging in mice. Science has a great piece on this fascinating area of science here. A sample:

The ITP “increases the chances that we will have at least one antiaging intervention that has an effect in humans,” says Jennifer Fox, project scientist for the effort. But turning its insights into treatments is difficult. The U.S. Food and Drug Administration (FDA) doesn’t consider aging a disease and won’t accept signs of delayed aging as an endpoint for clinical trials. Miller notes that one proposed trial, headed by geneticist Nir Barzilai of the Albert Einstein College of Medicine, did receive FDA permission to use indicators such as the occurrence of age-related conditions, including cancer and dementia. However, researchers haven’t been able to raise the $50 million needed to launch the trial, which would track 3000 older people taking the diabetes drug metformin for 6 years.

Cheers,

Colin

Reading Group Meeting #2 (Second Look)

This is the second installment of some notes and questions for the autumn reading group on this book (first post is here).

For this meeting we cover Part II- Thinking and Believing and Part III- Health and Safety.

Chapter 5 Creativity 

This chapter focuses on the story of Dick Fosbury, credited with transforming the way high jumpers attempted to clear the bar and who won the gold medal with this new technique in 1968.  Jumping over the bar with this technique is now standard, but it wasn't before Fosbury did it.  The authors note the following key elements of the success story of Fosbury and the "Fosbury-flop":

(1) need:  he was not very good at the forward-facing high jump.  If he excelled in that form of jump, there would have been no incentive to innovate!  So he experienced frustration with the traditional jump techniques.  This is a key element.

(2) ambition:  need is not sufficient (most of us are not accomplished forward-facing jumpers!)  Fosbury also possessed a strong determination to improve with his jumping skills.  

(3) small changes in the environment:  innovative thinking also requires some "nudge"- such as a small change in the environment.  In this case new landing surfaces made of soft foam rubber had replaced saw dust and wood-chip landing surfaces.  This change made it conceivable to innovate from landing on one's feet to one's back.

New environments stimulate flexible thinking.  The author's also note that a large literature also backs the contention that physical activity also boosts creativity. These things "gear the mind for change".

Question:  Reflect on your own experience of "creative thinking":  what things do you think either facilitate, or obstruct, your creativity?  I know for me, when I travel to live somewhere new for a few months of sabbatical I have my most productive research output (though many factors contribute to this).  I certainly observe a correlation between "novelty of experience" and "higher creativity/productivity".  What works to help you get out of a "rut"?

Chapter 6:  Lying

The brain habituates to lying.  So you want to prevent yourself or children from slipping from small little lies, which (once your brain habituates to the discomfort of lying) can lead to bigger and more frequent lies. The authors contend this has important political consequences in a "post-truth era".  Exaggerating facts to make one's point more interesting has become the norm.  The authors mention this Ricky Gervais movie- The Invention of Lying. 

Chapter 7:  (Mis)Information

The authors note that when falsehoods are repeated, eventually people come to think they are true.  Our brains habituate, initially being sceptical when we hear something new and/or surprising.  But as it becomes more familiar, this scepticism subsides. The authors argue that we function with a "familiar, truthier" heuristic. To try to incentivize accuracy, the authors suggest we may prompt people to consider just the accuracy of single statements (which could be enough to shift mindsets), or reward reliability by rewarding/punishing people for sharing true or false information online (strikes me as inherently problematic, presupposing that some admin overlord has the "book of truth and falsity" that they can then be impartially applied to steer the ignorant masses straight).

I found the gloss analysis of both lying and misinformation somewhat superficial.  I think lying/distortions/manipulations are much more pervasive and innate in our social nature.  Gossip, for example, is pervasive and serves many functions.  It is not touched on in the book, though I think is more representative of the lying and misinformation we habituate into our social lives.  It is so habituated that perhaps it wasn't something the authors thought to include in the book.  I would have liked to see the authors stretch their focus on habituation, moving away from the more obvious topical political examples.

Question:  Do you see the spread of misinformation online as a distinctive and pressing threat to the health of democracy?  Is it any different than the traditional ways in which misinformation has long been disseminated (e.g. through in-person conversations, radio, TV, etc.)?  Are attempts to police online social media posts for "accuracy" part of the ongoing "culture wars" (with the left and right both trying to suppress the information they feel is "misinformation"), or something the state must be proactive about to ensure modern democracy's can flourish?  

Chapter 8:  Risk

Risk habituation is the focus of this chapter.  People often rely on their feelings to assess risk, the more we habituate to the feelings of risky actions the more frequent and risky our behaviors may become.  We are more alarmed by new and unfamiliar risks (e.g. COVID).  The authors contend that the slogan "scared by the new, bold with the old" is an outgrowth of habituation.

When the Swedes switched from driving on the right side of the road to the left, there were less accidents and fatalities.  Why caused this counterintuitive result?  Risk dishabituation.  Two years latter the accidents and fatalities had returned to the baseline before the change.

A take home prescription the author's make is to "shake things up", by changing the environment, if you want to reduce risk.

Chapter 9: Environment

In this chapter authors explore how past exposure- to air pollution, light pollution, and water pollution- helps us adapt to these strains unconsciously.  

I'll share one personal example of this- in 2018 I lived in Hawaii for 3 months.  I lived in a small room, with only a bed, office desk and chair and bathroom.  There was no air conditioning and it was hot the whole time I lived there.  For the first week or two I would sweat a lot just laying on my bed.  I had to have two fans turned on full blast to feel somewhat comfortable.  And yet after that initial period I stopped perceiving the heat.  This was a real surprise.  After a month I forget that Hawaii was actually a hot place to live!

Question:  Can you think of any unpleasant experiences you have been adle to adapt to?  Or perhaps some things you have found challenging to adapt to?

Cheers, 

Colin

Impact of Lockdown on the Brain Aging of the Young

Even by the non-ideal standards of the pre-2020 world, I would have said it was inconceivable that the circumstances would ever arise where a study could be done on the brains of adolescents to measure the impact prolonged social isolation would have on their brains.  And yet in 2024 the PNAS has this study which examined the accelerated brain aging the COVID-19 lockdown measures had on the brains of boys and girls.  The Guardian covers the study here.

Using MRI structural data, the study examined the differences in male and female adolescent brain developing during the lockdown.  The study estimates that the brain maturation of girls was accelerated (on average) by 4.2 years, compared to 1.4 years for boys.  So these mitigation measures had a greater impact on the brain development of females.  This study does not get into the details of what that toll amounts to in terms of mental health, etc.  

Here is the abstract:

Adolescence is a period of substantial social–emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain.

Tragically few public health officials were vocal about invoking a precautionary approach to the deleterious effects of the lockdown measures, in terms of the harmful impact on the physical and mental health of children.  Such reasoning was selectively applied only to the potential deleterious effects of getting infected with the virus.        

Cheers, 

Colin 

25 Year Anniversary (Reflections on teaching)

As noted in my previous blog posts (see here and here) on the mark of 25 years of "professing", this post offers a few reflections on teaching.

Prior to teaching my first lecture course, I had approximately 5 years experience as a teaching assistant, which started in my final year as an undergraduate student for a critical thinking course.  I then TA-ed for intro philosophy as an MA student, and political philosophy as a PhD student.  My very first lecture course was in my final year of my PhD at the University of Bristol and it was to teach (on somewhat short notice) a full semester course on the thought of Karl Marx to approximately 40 students in year 2.  Luckily I had TA-ed that course the year before, but getting the lecture notes prepared was very labour intense.  This was back in the times when lecture notes were made on  acetate sheets for the overhead projector.  In the years to come, as I moved first to Aberdeen University, then Birmingham University and then to Manchester University I had to learn how to give lectures to large classes.  At Manchester, for example, I had to give lectures to the large 1st year course (300 students) and 2nd year theory course (200 students).  It was fortunate for me that I had about 3 years to refine my lecturing skills before doing larger classes.  In the first few years of teaching no class was larger than 60 students. 

By the time I was doing the large lecture course at Manchester power point had become a standard tool with large lectures.  I have a memory of using it in my first large class, with the text appearing on the screen  (unbeknownst to me) to the sound of screeching brakes!  I quickly learned the "ins and outs" of the new technology, and the feel for larger lectures, in that year at Manchester.  

I was always over prepared for my lectures (and probably still fall into that category).  I always had lectures prepared weeks in advance, and was prepared for the technology to fail (e.g. power point) so I had a backup plan prepared.  I once had a colleague who told me they would just scribble a few points on a napkin before their lectures, and then ad-lib the rest.  A stark contrast to my planning the content for each topic in the lecture, with critical quotations to cite, plus anticipating  various lines of questions students might ask (but rarely did).

Ironically the best thing to happen in a few large lecture courses was for the power point to fail, which first happened in a class of 200 students about 20 years ago.  I had to improvise, the room had a dated chalk board, and I managed to give a great lecture by relying on memory and jotting a few points on the board for all to see.  Once that happened my anxiety about the technology failing subsided as I knew I could manage if I had to.  In 2018 I actually went back to using chalkboard in a smaller lecture course of 60 students, and found it liberating.  But now my lecture courses are all large (close to 300 students), so I use power point exclusively.

I feel I really found my stride in teaching after around a decade of teaching.  I always enjoyed teaching from the beginning of my career, but once I felt my competence with the craft was more firmly established, my love for teaching flourished.  I enjoy teaching more now than at any other time in my career.  I see this as a blessing as I know this is not the experience of everyone in the teaching profession.  It is confirmation that I made the right decision in going into higher education as my vocation. 

I also attribute my love of teaching to my belief that research and teaching are intricately linked.  Over my career I have published 3 textbooks- here, here and (most recently) here.  I have never considered teaching as something that detracts from my research, but instead see it as integral to it.  On my sabbaticals in UCLA and Bilkent University I actually taught classes instead of taking the time away from all teaching.  And for over a decade at Queen's I taught an overload of courses, beyond what I was expected to teach.  I really benefit from the structure of having to be prepared to teach specific material at specific days and times during the fall and autumn teaching terms.  I continue doing research year round, but am always eager to get back to teaching after the summer term.  I enjoy engaging with students, their curiosity and enthusiasm fuels mine. 

Without a doubt the biggest challenge in the classroom for me over the past 25 years was the school closures during the pandemic.  I had to move all my classes fully online in 2020-2021, and ended up making over a hundred online lecture videos.  At first this was a really stressful process.  But then I became determined to make it the best experience possible for the students, to minimize the disruption to their education, and came to really enjoy the experience (though would prefer to always have the option of in-person instruction which I think is much better for both student and instructor).

Because I love teaching, I have no retirement plans on the foreseeable horizon.  I have taught thousands of students at 7 different universities in 5 different countries in departments of philosophy, political science and public policy.  And I look forward to making the most of all the future opportunities I get to play some small role in the intellectual development of more students, which in return helps ensure that I myself continue to grow and develop as both a scholar and teacher.  

Cheers, 

Colin

25 Year Anniversary (Research, post-PhD)

As noted in a previous post, this year marks 25 years in my academic career.  In this post I offer some reflections on a quarter of a century of research beyond the PhD.

25 years ago I had just defended my PhD thesis, a defence of Rawlsian justice that resulted in the following 4 journal articles:  

• Public Reason, Neutrality and Civic Virtues
• Justice and a Citizens' Basic Income
• Incentives and the Natural Duties of Justice
• Does Rawls Support the Procedural Republic?

As you can see from the focus of each of those articles, the central concern which preoccupied my research at that time was critically assessing the various lines of objection raised against John Rawls's theory of justice.  

Now let's fast forward 25 years and these are the last 4 publications from this year:  

• Classics of Political Thought for Today:  An Introduction
• The Role of Science Communication in Advancing Translational Gerontology
• Navigating the Landscape of Translational Geroscience in Canada:  A Comprehensive Evaluation of Current Progress and Future Directions
• Imagination and Idealism after the COVID-19 Pandemic:  The Science of Healthy Ageing

Looking at my most recent publications there would appear to be little, if any, continuity in my research interests over 25 years.  I will try to connect some of the dots here, reflecting on what I saw as key developments which shaped both my interests and the methodologies I utilize. I divide things into 4 distinct (though related) developments:

(1) My transition to non-ideal theory 

(2) The Genetic Revolution

(3) The Biology of Aging and Science Communication

(4) Side Burner Projects

(1) My transition to non-ideal theory 

I detail my transition from ideal to non-ideal theory in my book Justice, Democracy and Reasonable Agreement.  These included things like the terrorist attacks on Sept 11th 2001 and my switching from teaching in a philosophy department to political science departments.  And my research interests in the biomedical sciences was really pivotal as I will detail below in (2).  

Shortly after my PhD I can recall a few important conversations with senior figures in the field that compelled me to re-think my research plans after the PhD.  One comment was something a prominent figure in the field asked me during a job interview I was giving at their department (a job I was not successful in getting).  During the interview this person said:  "I have read your articles defending Rawls against communitarian critiques, and the Rawlsian position on basic income, but when are we going to hear about what Farrelly's position is on issues?"  This question stuck with me over 25 years later because at that time I did not have the self-awareness to consciously reflect on my own intellectual development with much depth.  Indeed, looking back to the state of the discipline in the 1990s I do not think analytical political philosophy encouraged much internal critical reflection.  It was mostly a "puzzle solving" endeavor, with distinct "camps" and most scholars simply aligned themselves with their favorite camp and then worked on the puzzles that camp was interested in solving (e.g. equality of what?  liberal vs communitarian?  deliberative democracy ? etc.).

In my second academic appointment in my second year post-PhD a senior colleague had recommended I publish my thesis as a book, that this was the most straightforward and obvious route to career advancement.  But I told him hat I did not think my thesis was "book worthy", and that instead I was undertaking the process of writing a textbook on contemporary political theory.  Looking back I realize how risky my decision was (fortunately it paid off for me, but I would not advise recent PhDs to follow my strategy!).  My gamble paid off in that by undertaking the research necessary to write a textbook I acquired a breadth of understanding and perspective that I was previously lacking.  Once I had expanded my intellectual horizons by just a little bit, the chinks in the armor of Rawlsian liberalism had, for me, become insurmountable.  I ended up publishing my first research monograph, what I call my "anti-thesis", Justice, Democracy and Reasonable Agreement (this book appeared in print 8 years after my PhD). 

A recurring theme in those early years was intellectual risk-taking:  taking the risk of moving from philosophy to political science, taking the risk of writing my first book as a textbook, and taking the risk of turning against the theory I defended in my PhD, and arguing for non-ideal theory which, at at the time around 2005, was still virtually unheard of.   

(2) The Genetic Revolution

Another big shift in my thinking was taking place in the early 2000s, a result of my growing interest in the sequencing of the human gnome and the development of new gene therapies for rare, but devastating, genetic disorders.  Initially I approached this topic from a standard Rawlsian perspective-- "The natural lottery of life is the result of brute luck, so as science innovation makes it more feasible to ameliorate these "natural inequalities", justice will require a fair distribution of natural endowments".  This article, written over a long Easter weekend in 2000, was my initial foray into this area. This excellent book was also published, by the most prominent scholars in the field, and proved the perfect assigned reading for the new course I designed on that topic.  

The first year I taught the course "Genetics and Justice" was with my excellent colleague at Manchester. Sadly we only co-taught the course for one year, as I took up a position back in Canada.  But that course remains my favorite course to teach and I have been offering it every year since 2002.  As I began to follow the science closely, I realized that ideal theory was ill-equipped to address the issues.  There were complexities like the causes of disease (genes, environment, and the interaction between the two), and uncertainties about both the safety and efficacy of new biomedical innovations like gene therapy (and later genome editing).  There were also issues like the amount of funding to bring new drugs to development, and intellectual properties rights.  To invoke an ideal theory analysis would mean circumventing all these nuances of the real world, which struck me as just a lazy and pointless route to take.  So instead I devoted more than a decade to undertaking the interdisciplinary research necessary to competently integrate normative analyses of the issues with the science. 

While I eventually became a critic of Rawlsian justice, the dominance of his theory in the field proved a useful frame to enable me to develop my ideas around "well-ordered" science, pivoting between political philosophy and bioethics, the culmination of which was this research monograph and a textbook.  However, about 4 years into the research monograph I realized the issues I was grappling with could not be meaningfully resolved by appeals to ideal theory.  I recall a prominent scholar was giving a talk on the issue of biomedical enhancements, and a premise of their argument was that these interventions had to be (immediately?) available to everyone in order to be permissible to develop.  When I asked a question about what their view was for the real-life situation, where no scientific innovation comes into existence being accessible to all of the world's population, they just replied that they were analyzing the issue from the perspective of ideal theory.  The old Colin may have been content with such a reply, when it would have functioned like a secret society's handshake (e.g. aren't you a member of the Rawlsian ideal theory club?).  But to me the comment was not only unhelpful, I felt it was disingenuous.  Theorizing about technologies developed in a fantasy utopia seemed counterproductive to the whole exercise.  If one is functioning with utopic presumptions at play, why not simply assume humans were already enhanced, making any biomedical innovations obsolete.  Alas, that was precisely the predicament that Rawlsian ideal justice had created, as very few political philosophers took (or still take) seriously disease, aging and biomedical science.  

(3) The Biology of Aging and Science Communication

The most significant development in my research interests during this time came from learning about advances in the biology of aging.  This topic has driven most of my journal publications in the last 15 years, in journals in science, medicine and bioethics.  This topic excited my intellectual curiosity like no other.  It raised fascinating questions like "Why do we age?" and "Is it possible to alter the rate of aging?" and "What would the societal implications of translational gerontology be?"  My initial knee-jerk reaction to the prospect of altering aging was that claiming it was an imperative was analogous to claiming that it was a priority to cut taxes for millionaires.  Luckily around 2006, I had become much more interdisciplinary about my research interests, and rather than contemplating the issue of longevity science within the scant discussions developed by philosophers, I emersed myself in both the literature on the growing field of geroscience, as well as the intellectual history of medical science.  And this proved to have significant and far-reaching impacts on my research over nearly 20 years.

20 years ago I would aspire to publish in mainstream political philosopher journals, like these two that have recently folded (though they could be revived).  Now I conceive of my potential readership much more broadly, covering researchers in both the natural sciences and humanities/social sciences, as well as policy makers.    

One of the truly rewarding (though also burdensome and at times frustrating!) features of undertaking interdisciplinary research is you receive feedback from scholars in diverse disciplines.  I have received dozens of referee reports from experts in different areas of science, which has helped me to further refine my understanding of the issues and my broader intellectual development.  One quickly learns that there are distinct "camps" within all fields of research, and learning what divides those camps (e.g. different empirical assumptions or communicative frames) can facilitate better understanding (and success with publishing).  

The latest substantive research interest of mine, which has emerged from communicating the social significant of translational gerontology, is the role of science communication (more broadly construed) within democracy.  I feel that this topic alone could sustain my research interests for the next quarter of a century.  

(4) Side Burner Projects

The core research areas of mine of the past 25 years fall into:  non-ideal theory, genetics and justice/ethics, play (still ongoing, though on the back burner for now), geroscience, and the contemporary relevance of the history of political thought.

But I also have smaller, side projects, that I have kept burning over the years that enable me to satisfy other intellectual curiosities I have.  So taken together these projects easily equal any one of the large projects in terms of providing intrinsic rewards from research.  These are the side-burner projects:

1. Marx's theory of history (here and here)
2. Legal theory (here, here, here and here)
3. Virtue epistemology (here, here and here)

The great thing about side-burner research projects is that (a) they compel you to keep some breadth in your research interests vs becoming overly specialized in just one scholarly niche; (b) they are purely motivated by the intrinsic rewards of satisfying your curiosity (vs one's main research projects for getting tenure and promotion); (c) you never know when side projects might turn into "main projects".  I never would have predicted, after my PhD defence,  any of the 3 main research projects  that came to subsume most of my research over the following 25 years.  

Side-burner projects help remind me what a privilege it is to be employed as a scholar.  Indulging my side-burner research interests feels more like undertaking an eccentric hobby I don't have much time for vs part of my paid employment.  So I have been extremely fortunate in that my love for research and writing is higher now than at any other point in my career.  I could not envision a meaningful life for me that did not entail many hours of intense study and writing most weeks of the year.  The life of a scholar is one of immense responsibility and privilege.  I have been able to pursue my intellectual development and curiosity, in exchange for disseminating that knowledge through academic publications and teaching and mentoring of students.  

One final point about a key (and conscious) decision that I made over a decade ago that I think has served me well research-wise-  I do not let the frenzied, and often combative, domain of social media play any substantive role in shaping either my research interests or the substantive positions I take on important issues.  I have been running this blog, with comments off, for 18 years.  It is really just an opportunity for me to "float ideas" I'm working on by thinking out load, note scientific studies I may want to keep track of etc.  But I do not engage in protracted debates or arguments with scholars on social media.  I think those things are best approached through the forum of peer review publications.  

A low profile on social media has not only been beneficial to my mental health, but I believe it has positively impacted my research agenda.  Avoiding the constant distraction, and echo chamber effect, of social media has probably helped me stay focused on the intrinsic rewards of satisfying my intellectual curiosity. It does come with some cost given that a strong online presence with many followers can build some social capital within academia.  But for me I am ok with that.  Having started my career before social media was a thing, I have enjoyed staying more oriented towards the "pre-social media" mentality.  An orientation that intentionally seeks to cultivate a practice of interdisciplinary "deep thinking" working towards the goal of peer reviewed publications (with the occasional blog post reflection).  Engaging in daily debates on social media about the "hot topics" of the week has never held any appeal for me, and runs counter to what I take to be the spirit of a serious scholar to be (e.g. curious and civil, committed to raising the quality of dialogue and debate).    

In my next follow up post I will offer some reflections on 25 years of teaching.

Cheers, 

Colin