The Best-Laid Schemes of Mice and Medical Researchers…

This is Dr. Ellen Heber-Katz. She’s an internationally-renowned immunologist and regeneration biologist, but her perhaps greatest discovery was accidental.

Unlike in Robert Burns’ famous poem, this one has a happy ending!

But it did involve the best-laid schemes of mice and medical researchers, and how they did indeed “gang gagly“ (or in the English translation, “go awry”).

How it started…

Back in 1995, she was conducting autoimmune research, and doing a mouse study. Her post-doc assistant was assigned to punch holes in the ears of mice that had received an experimental treatment, to distinguish them from the control group.

However, when the mice were later checked, none of them had holes (nor even any indication there ever had been holes punched)—the experiment was ruined, though the post-doc swore she did her job correctly.

So, they had to start from scratch in the new year, but again, a second batch of mice repeated the trick. No holes, no wounds, no scarring, not disruption to their fur, no damage to the cartilage that had been punched through.

In a turn of events worthy of a superhero origin story, they discovered that their laboratory-made autoimmune disease had accidentally given the mice super-healing powers of regeneration.

In the animal kingdom, this is akin to a salamander growing a new tail, but it’s not something usually found in mammals.

Read: A New Murine Model for Mammalian Wound Repair and Regeneration

How it’s going…

Dr. Heber-Katz and colleagues took another 20 years of work to isolate hypoxia-inducible factor-1a (HIF-1a) as a critical molecule that, if blocked, would eliminate the regenerative response.

Further, a drug (which they went on to patent), 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), chemically induced this regenerative power:

See: Drug-induced regeneration in adult mice

Another 5 years later, they found that this same drug can be used to stimulate the regrowth of bones, too:

An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during resolution of experimental periodontitis

And now…

The research is continuing. Here’s the latest, a little over a month ago:

Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration

Regrowing nerves has also been added into the list of things the drug can do.

What about humans?

Superpowered mice are all very well and good, but when can we expect this in humans?

The next step is testing the drug in larger animals, which she hopes to do next year, followed eventually by studies in humans.

Read the latest:

Regrowing nerves and healing without scars? A scientist’s career-long quest comes closer to fruition

Very promising!

The Best Brains Bar Nun?

This is Dr. David Snowdon. He’s an epidemiologist, and one of the world’s foremost experts on Alzheimer’s disease. He was also, most famously, the lead researcher of what has become known as “The Nun Study”.

We recently reviewed his book about this study:

Aging with Grace: What the Nun Study Teaches Us About Leading Longer, Healthier, and More Meaningful Lives – by Dr. David Snowdon

…which we definitely encourage you to check out, but we’ll do our best to summarize its key points today!

Reassurance up-front: no, you don’t have to become a nun

The Nun Study

In 1991, a large number (678) of nuns were recruited for what was to be (and until now, remains) the largest study of its kind into the impact of a wide variety of factors on aging, and in particular, Alzheimer’s disease.

Why it was so important: because the nuns were all from the same Order, had the same occupation (it’s a teaching Order), with very similar lifestyles, schedules, socioeconomic status, general background, access to healthcare, similar diets, same relationship status (celibate), same sex (female), and many other factors also similar, this meant that most of the confounding variables that confound other studies were already controlled-for here.

Enrollment in the study also required consenting to donating one’s brain for study post-mortem—and of those who have since died, indeed 98% of them have been donated (the other 2%, we presume, may have run into technical administrative issues with the donation process, due to the circumstances of death and/or delays in processing the donation).

How the study was undertaken

We don’t have enough space to describe the entire methodology here, but the gist of it is:

• Genetic testing for relevant genetic factors
• Data gathered about lives so far, including not just medical records but also autobiographies that the nuns wrote when they took their vows (at ages 19–21)
• Extensive ongoing personal interviews about habits, life choices, and attitudes
• Yearly evaluations including memory tests and physical function tests
• Brain donation upon death

What they found

Technically, The Nun Study is still ongoing. Of the original 678 nuns (aged 75–106), three are still alive (based on the latest report, at least).

However, lots of results have already been gained, including…

Genes

A year into the study, in 1992, the “apolipoprotein E” (APOE) gene was established as a likely causative factor in Alzheimer’s disease. This is probably not new to our readers in 2024, but there are interesting things being learned even now, for example:

The Alzheimer’s Gene That Varies By Race & Sex

…but watch out! Because also:

Alzheimer’s Sex Differences May Not Be What They Appear

Words

Based on the autobiographies written by the nuns in their youth upon taking their vows, there were two factors that were later correlated with not getting dementia:

• Longer sentences
• Positive outlook
• “Idea density”

That latter item means the relative linguistic density of ideas and complexity thereof, and the fluency and vivacity with which they were expressed (this was not a wishy-washy assessment; there was a hard-science analysis to determine numbers).

Want to spruce up yours? You might like to check out:

Reading, Better: Reading As A Cognitive Exercise

…for specific, evidence-based ways to tweak your reading to fight cognitive decline.

Food

While the dietary habits of the nuns were fairly homogenous, those who favored eating more and cooked greens, beans, and tomatoes, lived longer and with healthier brains.

See also: Brain Food? The Eyes Have It!

Other aspects of brain health & mental health

The study also found that nuns who avoided stroke and depression, were also less likely to get dementia.

For tending to these, check out:

• Two Things You Can Do To Improve Stroke Survival Chances
• Depression, And The Mental Health First-Aid That You’ll Hopefully Never Need
• Behavioral Activation Against Depression & Anxiety

Community & Faith

Obviously, in this matter the nuns were quite a homogenous group, scoring heavily in community and faith. What’s relevant here is the difference between the nuns, and other epidemiological studies in other groups (invariably not scoring so highly).

Community & faith are considered, separately and together, to be protective factors against dementia.

Faith may be something that “you have it or you don’t” (we’re a health science newsletter, not a theological publication, but for the interested, philosopher John Stuart Mill’s 1859 essay “On Liberty“ makes a good argument for it not being something one can choose, prompting him to argue for religious tolerance, on the grounds that religious coercion is a futile effort precisely because a person cannot choose to dis/believe something)

…but community can definitely be chosen, nurtured, and grown. We’ve written about this a bit before:

• How To Beat Loneliness & Isolation
• Make Social Media Work For Your Mental Health

You might also like to check out this great book on the topic:

Purpose: Design A Community And Change Your Life – by Gina Bianchini

Want more?

We gave a ground-up primer on avoiding Alzheimer’s and other dementias; check it out:

How To Reduce Your Alzheimer’s Risk

Take care!