This week, I am attending, and presenting at, two major conferences held at the Buck Institute, the nation’s leading center for longevity research. The topic – biomarkers of aging. So, this is a good time for me to reflect on how aging biomarkers became so central to my work and how, in the longevity world, this approach has evolved so dramatically over the past few years. And perhaps most importantly – why you should care.
Let’s begin with some ancient history. Twenty-five years ago, I began to build my longevity clinic practice on the foundation of biomarkers of aging. I rejected the premise that the best way to treat patients was to give them a battery of standard tests (blood pressure, cholesterol, etc.), pat them on the back if their results fell within the normal range, pull out the prescription pad if they didn’t. Instead, I, and a handful of other pioneers like Dean Ward and Richard Hochschild, conceived of the health of each major physiological system as a continuum, stretching from the optimal function of a fit person in their twenties to that of the older patient whose poor lifestyle choices (exercise, diet, sleep, stress, etc.) were doing nothing to slow down the march of age-related decline. The overarching mission was not to divide my patients into two camps, the sick and the well, but rather to work with each patient to maximize their strengths and shore up their weaknesses.
Then as now, our functional tests generate results that are couched in terms of biological age, for instance CardioAge, a measure of arterial stiffness, and PulmoAge, a measure of maximum breath exhalation. My patients are sometimes, to put it mildly, confused: “This is nuts! How can my cardiovascular system be 50, and my lungs 55?” (Or, as I titled an Instagram post from last year: “It’s raining Biomarkers of Aging, but none of them agree!”) The explanation isn’t complicated. Each biomarker measures a specific system – brain, cardiovascular, pulmonary, immune, hormonal, and so on. While the health of one system often influences the others, they all still age at different rates. (A recent paper in Nature Aging dove into some complex molecular biology to illustrate that point: “The genetic architecture of biological age in nine different organ systems.”) The age of each system reflects your genetic inheritance (maybe you were born with a barrel chest and big lungs) as well as how your life and lifestyle has modified the genetic cards you were dealt (maybe you’re a recreational runner or, heaven forbid, a pack-a-day smoker).
This biomarkers approach to a more personalized medicine allows us to catch any slippage (meaning, a concerning increase in “age”) before it becomes a threat to health or life. And, correspondingly, the efficacy of any lifestyle change or therapeutic intervention (hormone replacement or supplementation being, in my view, the most potent) can be measured by how much it moves the needle, how effectively it lowers our various system-specific “ages.”
These are important concepts but, frankly, not brand-new. What has breathed fresh excitement into the field, and spawned scores of lively scientific conferences, is the development of fancier hi-tech bio-markers of aging, or, to use the more up-to-date lingo, “clocks.” About a decade ago, UCLA researcher Steve Horvath introduced a novel way to measure biological age, by measuring the predictable changes in the epigenetic markers that turn our genes on and off, over the course of the human lifespan. We, in the field, were initially enthralled by this idea of a biochemical “clock.” Seemingly, we could “watch” aging like the moving hands of a clock. But because this clock was “trained” on chronological age -- Horvath sought out methylation patterns that corresponded to actual years on the planet -- it produced an epigenetic age that was extremely close to chronological age. That was its downfall, so tightly bound to chronological age, it didn’t provide much in the way of useful or actionable information. (After all, we already know our chronological age!)
But Horvath’s clock gave rise to later generations of clocks, trained on real, malleable physiological processes. Clocks like PhenoAge and SymphonyAge derive epigenetic read-outs from the body’s major physiological systems. Consequently, they produce system-specific “ages” that reflect chronological aging, but only roughly. It is the distance between the biological ages they produce and actual chronological age that is the space that the longevity clinician works in, upgrading lifestyle habits and, when appropriate, trying out therapeutic interventions. Were these changes successful? These epigenetic ages will tell us, or at least, strongly suggest.
Yes, the evolution of aging clocks has been circular, bringing us back to the original conception that launched my practice, measuring the function of different body systems at a more macro level. So, these days, I integrate both the physiological biomarkers and the best of newer clocks into my practice. While science still hasn’t come up with a “grand unified theory” of aging, and may never do so, thanks to our biomarkers/clocks, we’re getting better and better at identifying and treating its effects.
Mahdi Moqri, et al. Biomarkers for the Identification and Evaluation of Longevity Interventions Interventions. Cell. 2023 Aug 31;186(18):3758-3775. doi:10.1016/j.cell.2023.08.003
Wen,J., Tian, Y.E., Skampardoni, I. et al. The genetic architecture of biological age in nine human organ systems. Nat Aging 4, 1290-1307 (2024). https://doi.org/10.1038/s43587-024-00662-8
Comments