We in this section offer commentaries on a broad survey of recent articles. Articles are mostly chosen for two reasons: their potential translational value for immediate clinical practice or to help in determining where clinical practice might evolve to. Today’s subjects are of general medical interest but have clear relevance to reproductive medicine.

Unexpected shifts in cell populations are changing the understanding of aging

As we already noted in the short piece on Harvard University’s Professor Sinclair, the question of what human aging really represents has remained highly controversial, with Sinclair likely being the most controversial “expert” for claiming it to represent a reversible disease. Now comes research from the Laboratory of Single Cell Genomics and Population Dynamics of Junyue Cao, PHD at Rockefeller University in NYC which offers important new insights on tracking organ development at the single cell level. Single-cell sequencing is not easy but has become a specialty of the Cao laboratory at Rockefeller. This technology makes visible the genetic expression and molecular dynamics in individual cells, while at the same time showing the exact identity of each cell. Cao recently for this achievement was awarded the Science & SciLifeLab Prize For Young Scientists (2).

The laboratory originally developed the technique for studies of aging in the brain but now expanded it to every single major organ in a mouse (quite an accomplishment!) (1). In a recent Science magazine Essay, Cao started explaining his work by noting that every human, of course, develops from a fertilized egg (i.e., a single cell) which divides into two cells, which then divide over and over again until a complete organism is created, made up of trillions of cells of hundreds of cell types (2). Now scanning in a mouse millions of cells from every organ across five stages of life, he created the world’s largest cellular atlas in a single study and reported amazing observations: Certain cell population undergo the same changes, at the same time, in every organ during very specific stages in life.

In other words, it appears that aging is not – as widely perceived – a gradual linear process, but – based on the timing of certain molecular signals – which affect all organs at the same time. Aging, therefore, appears to happen stepwise and Cao argues that those individual aging steps, therefore, may be delayable or even completely avoidable by reprogramming of those molecular signals.

Using cells from more than 600 female and male mouse samples at above noted five different stages of life, the laboratory discovered 10 main cell types and roughly 200 subtypes which consistently depleted or expanded at certain age. Age 3-12 months (early adults in mice) very specific subtypes, for example, dropped significantly in numbers in fat, muscle, and epithelial tissues, while at 12-23 months (advanced adults) immune cells increased hugely. Especially B lymphocyte subtypes were affected by this expansion, potentially explaining the increase in inflammatory and autoimmune diseases with advancing age.

How important the immune system appears to be in aging was demonstrated in immunodeficient mice that lacked these B lymphocyte subtypes as well as T lymphocytes affected significant changes in other cell types associated with aging.

We would argue that not unexpectedly (others feel differently (1)), the researchers also found significant sex-based differences, in turn potentially explaining why women demonstrate a so much higher prevalence of autoimmune diseases than men (though men, often, have more severe disease).

If these periodic changes in different cell populations are also confirmed in humans, the potential therapeutic applications are, of course, enormous. And, while this periodic aging pattern cannot be considered a disease – and may not be reversible (but who knows?), it would at least appear delayable and, maybe, even preventable to a degree.

REFERENCES

1. Science News. The Rockefeller University. December 11, 2024. https://www.rockefeler.edu/news/36993-study-reveals-how-unexpected-...ell-populations-are-revising-our-understanding-of-the-aging-process/

2. Cao J. Science 2024. https://www.science.org/doi/10.1126/science.abf1686

Did you know that taxi drivers are somewhat protected from Alzheimer’s disease

The only blog we are paying as much attention to as Eric Topol’s Ground Truth, is the Impact Factor, the amazing blog of Yale’s F. Perry Wilson MD, MSCE. In his December 17, 2024, posting he, once again, offers a masterpiece in statistical clarity by explaining the curious reasons why taxi drivers apparently are protected from Alzheimer’s disease. And – yes – this is not a misprint; they really appear protected (1)!

His blog starts with an explanation of how important the hippocampus in the brain is for converting short-term into long-term memories and for forming spatial memory, the basis for our ability to navigate in complex ways. And when Alzheimer’s starts to become clinically apparent, the hippocampus is the first brain region affected and, with it, memory and orientation.

Already in the year 2000 a British study of London cab drivers reported that their hippocampi were much larger than normal and the longer they had been in the profession, the larger they were (2). And the only explanation for this finding was that cab drivers; hippocampi had to work overtime to orient themselves in a city as complex as London (the obvious follow-up study one now would be expect is a determination whether the introduction of computerized navigation systems to the taxi industry may reverse this finding and make taxi drivers again more susceptible to Alzheimer’s).

This figure demonstrates as expected a rise in Alzheimer’s in the general population with advancing age (gray circles); but the low death rate from Alzheimer’s (though at relatively young age) of taxi (blue circle) and ambulance drivers (orange circle) is remarkable

The blog was motivated by a more recent paper that had appeared in the BMJ (3) and assessed disease mortality from Alzheimer’s among taxi and ambulance drivers, which demonstrated – this time in a very large patient population of 8,972,221 – that taxi and ambulance drivers, indeed, demonstrated the lowest death rate from Alzheimer’s among 443 professions during the period of January 1, 2020, and December 31, 20223 (see figures above)

**This figure demonstrates that these two professions demonstrated the lowest adjusted risk for**
**death from Alzheimer’s from among 443 professions.** Source: *Impact Factor*

But this figure demonstrates that both professions do not protect from other than Alzheimer’s Dementia, offering support to the hypothesis that size of the hippocampus has specific Protective effects for Alzheimer’s disease. Source: *Impact Factor*

References

1. Wilson FP. Impact Factor. December 17, 2024. https://www.medscape.com/viewarticle/curious-reason-taxi-drivers-are-protected-alzheimers-2024a1000n9h

2. Maguire et al., Biol Sci 2000;97(8):4398-4403

3. Patel et al., BMJ2024;387:e082194

GENERAL MEDICAL LITERATURE REVIEW

LITERATURE for the INFERTILITY CLINIC

GENERAL MEDICAL LITERATURE REVIEW