Medicine Beneath the Surface: Redefining Aging, Disease, and Longevity Medicine

A lot of words and a lot of conference time have been expended on a single question: “Is aging a disease?” Or, to put it in more concrete terms, are doctors specializing in longevity medicine just treating the common “diseases of aging” more assiduously than some of their mainstream medical counterparts, or are they beginning to push back against the aging process itself?

My answer? We’re asking the wrong question. Whether aging is an immutable property of being alive or a pathology that might someday be partially or totally “cured” is a philosophical question that doesn’t yield practicable answers. Not yet anyway. The question that I ask, and it informs my entire longevity medicine, is: when do the common “diseases of aging” begin to take root in the human body?

Where conventional medicine sells us short is by dividing patients into two camps, the healthy and the sick. If, for instance, you have a fasting glucose of 126 mg/dl, you’re diabetic, or an ejection fraction below 40%, you’re considered to be in the first stage of heart failure, or an MMSE under 24, you’ve got dementia. But these thresholds are relatively arbitrary. A disease of aging isn’t a binary proposition, i.e., you have it or you don’t. It’s a continuum and it has a trajectory. If we can identify a disease process beginning to take shape, in what’s called the “prodromal stage,” then we can intervene with more impact, stopping it from reaching the point where it would be even recognized as disease by conventional medicine. In fact, even using the term “disease” can often be misleading. Instead of asking, “has the disease begun?,” longevity medicine doctors want to know how far and how quickly, any of the systems of the body – cardiovascular, neurological, immune, hormonal, metabolic, etc. – have drifted from the peak function of their second or third decade And, working together, how patient and doctor can slow or reverse that decline.

That’s a challenge we can meet because, over the past several decades, in some cases, in the past year or two, we’ve developed a more refined set of assessment tools to capture the physiological erosion that defines aging. We combine functional tests measuring, for instance, cardiovascular, cognitive and pulmonary performance; blood tests that can pick up proteins concerning for Alzheimer’s and cancer; and, at the molecular level, tests that measure epigenetic change. It is, in sum, a “biomarkers of aging” approach to health and sickness.

Picture it this way. A diagnosis of atherosclerosis or early-stage dementia represents the visible portion of an iceberg. But most of the ice mass lies under the waterline. Imagine our diagnostic protocols as the diver who descends to the deeper layers where the ice first began to take shape and then follows the berg to the surface, assessing the damage along the way.

The deepest level where we can effect positive change is the epigenetic. While our genes are set before birth, the chemical messengers that determine which genes are expressed, and when, our epigenome, are very much influenced by our lifestyle choices – exercise, diet, stress management, social engagement. Using tests licensed from major academic centers, we can measure changes in the epigenome that give us an idea, not only of our overall “rate of aging,” but how well, or not so well, individual organ systems are declining in function, in other words, how fast or slow their “biological clocks” are ticking. That helps us tailor lifestyle recommendations to the patient – a healthy lifestyle is still the bedrock of preventive medicine – and helps us determine which supplements and possibly drugs might be added to the therapeutic mix.

As we ascend the sunken berg, the next stratum we encounter are the proteins that our genetics and epigenetics have directed the body to produce. We analyze proteomic signatures, that is patterns of proteins involved in, for instance, enzymatic reactions or cell-to-cell signaling, or inflammatory responses. We’re on the lookout for elevated risk for disease before it manifests, for instance, a test for the pTau217 protein that can predict the likelihood of Alzheimer’s decades before dementia becomes evident. We also make use of new technology with tests like GlycanAge, which measures inflammation at the level of a particular immune system antibody, and SapereX, which analyzes T cell gene expression in order to get a snapshot of cell senescence and autophagy, key aspects of immune system function and aging. Finally, at the cell level and tissue level, we’re approaching the surface and more visible disease.

What I and my likeminded longevity medicine peers are doing every day is learning how best to integrate all of this biomarker data to derive the most accurate and actionable treatment plans for our patients. Given that heart attacks are still the leading cause of death in the Western world, let’s zero in on the cardiovascular system. An epigenetic test that measures the biological age of the heart can give us an early warning about increased cardiovascular disease risk. But it won’t tell us much about the actual mechanisms driving up that risk. (As these epigenetic “clocks” continue to be refined, they’ll likely give us a fuller picture of the early disease process but, to date, they’re still a work in progress.) To assess that, we go beyond the basic LDL/HDL testing to measure lipoprotein (a), a too-often ignored CVD bad actor. We’ll want to see if there’s an atherosclerotic process actually beginning to take shape, with hi-tech imaging diagnostics like the AI-interpreted Cleerly CTA (computed tomography angiogram).  

Finally, at the “surface” functional level, using the Sphygmocor device, we’ll measure the stiffness of the major vessels that carry blood to and from the heart, which gives us a better indication of vascular aging than the standard blood cuff measuring brachial blood pressure. Years before your blood pressure rises to a level that would raise eyebrows at an annual physical, a read-out of mediocre arterial flexibility suggests elevated risk for heart attack as well as heart failure, an increasingly common diagnosis for patients in their elder years. As the old maxim has it, forewarned is forearmed.

In The Prince (1532), Niccolò Machiavelli wrote: "In the beginning, a disease is easy to cure but difficult to diagnose; but as time passes, not having been recognized or treated at the outset, it becomes easy to diagnose but difficult to cure."  What Machiavelli observed in politics applies elegantly to human biology: timing is everything. With the help of sophisticated biomarkers, when we intervene when physiological imbalances are subtle, and the system remains pliable, we can finally prevent disease rather than simply treat it. That, I hope, will become the framework for good medicine, not just longevity medicine. In a very real sense, they’re the same thing. 

What I haven’t talked about here is the possibility of significantly expanding maximal human lifespans. And yes, there is intriguing basic science being done that suggests that someday it may be possible to push beyond a hundred years plus on the planet. I’m certainly interested. But whether that day arrives or not, my goal as a clinician is to give my patients and readers, and, for that matter, me, an expanded “healthspan,” more years of disease-free living. We want to be the most robust 90-year-olds we can possibly be.