MIKE MAGEE
In the final summary of the landmark paper, published last month in Nature, the authors said: “This study highlights the highly personalized nature of thymic health and highlights the previously unrecognized critical role of maintaining thymic health to preserve agile and adaptive immune responses that will accommodate long-term well-being and longevity.”
The clinical significance of the article was quickly rebroadcast through various popular science publications, such as Scientific American. A March 18 headline read: “This overlooked organ may be more important for longevity than scientists realize.” A Mass General publication touted, “Adult health has been neglected for so long that the thymus may be important for longevity and cancer treatment.” And the global outlet goes further, stating, “The thymus, once thought to be biologically useless after puberty, is now being reclassified as a key regulator of immune aging, with new evidence linking thymic health and survival, cancer resistance, and the body’s aging process.”
The authors of the Nature publication were a bit more cautious in their abstract, but the message is still surprisingly important. “These findings reposition the thymus as a central regulator of immune-mediated aging and disease susceptibility in adulthood, highlighting its potential as a target for preventive and regenerative strategies to promote healthy aging and longevity,” they wrote.
But what I found interesting about the above case was something that the reviewers, who were very excited about the primary clinical results, barely mentioned. My question was, “How did you measure thymus function?” The short answer is that it was measured with the help of an AI deep learning system.
The authors write, “In this study, we investigated the impact of thymic function, termed thymic health, in adults… To quantify thymic health, we developed a deep learning system using an independent data set of 5,674 individuals to determine the compositional radiomic properties of the thymus as a proxy for function. The system uses CT scans as input and provides automated continuous thymic health estimates as output… We modeled the system on prospectively collected data from a total of 5,674 individuals. We applied 27,612 participants from two cohorts, including 2,581 FHS participants and 25,031 NLST participants… For outcome analysis, participants were classified as having low, average, or high thymic health based on the bottom 25%, middle 50%, and top 25% of the population.”
This new methodology for demonstrating different levels of thymic function proved groundbreaking when cross-referenced with a longitudinal database spanning several decades. Association with cardiovascular disease and lung cancer; History of smoking, obesity, and high HDL levels; disability, disease and mortality; Both gender and age reinforced the finding that long-term function of the thymus is associated with health and longevity.
For example, they said, “As expected, thymus health was higher in women than in male participants and decreased significantly with age.” But beyond that, the authors delve deeper into the link “between metabolism and thymic health,” concluding, “These findings suggest a profound impact of actionable lifestyle choices on thymic health and may further clarify why healthy behaviors improve well-being and longevity.”
Finally, calculations using several chemical markers of inflammation showed that “lower thymic health was indeed associated with pro-inflammatory alterations in plasma protein levels consistent with the presence of chronic inflammation. The pro-inflammatory pattern included increased levels of the cytokines IL-6, IL-18, and OSM, as well as several CXCL chemokines, all of which are associated with atherosclerosis, age-related diseases such as arthritis, and cancer.”
In the final summary, the authors get to the gold ring when they say, “This study highlights the highly individualized nature of thymic health and highlights the previously unrecognized critical role of maintaining thymic health to preserve agile and adaptive immune responses that will accommodate long-term well-being and longevity.”
And it’s understandable that you’ll end up with such a “good news” clinical record. But we must be careful not to bury clues here. Generative AI, which assists researchers in creating methodologies that can more accurately measure what was previously unmeasurable, has reset what is “possible” in the pursuit of health and longevity. But more importantly, the paper suggests that using “deep learning systems” to extend functional measurements beyond what we see, feel, or have always believed to be true could accelerate discovery at a previously unimaginable rate.
Mike Magee MD is a medical historian and regular contributor to THCB. He is the author of: Code Blue: Inside America’s Healthcare Industrial Complex. (Grove/2020)
