Why do we all age at such different rates?

Among the many acquired skills possessed by nightclub bouncers is that of accurately guessing someone’s age from nothing but their external appearance. An even more rarefied skill would be to be able to guess how long their patrons might continue to live. To do that some kind of internal measure of aging, an internal ‘biological age’ meter is probably needed. In a paper just published in PNAS, researchers have attempted to do just that. By pooling several quantitative biomarkers they were able to predict the physical and mental performance of test subjects on tasks designed to assess their actual biological age.

Provided you are willing to chop down a tree, it is easy enough to determine its age by simply counting the annual rings it grows. The same can be done for fish by counting the layers on the otoliths they use for balance, hearing, and buoyant control. These are the finely suspended calcium carbonate creations beneath their brains that are somewhat analogous to our own middle and inner ear structures. Remarkably, researchers have been completely unable to come up with any kind of natural, seasonal, or otherwise regular indicator of human age.

One might imagine that if we look hard enough, or pool enough rough indicators we might be able to make a decent guess. For example, variances in cosmic ray mutational events as Earth makes its regular transits, or climate-driven irregularities in absorption of signature atomic fallout events might theoretically do the trick. But those are generally hard things to try to measure. The authors of the recent PNAS paper instead looked at a diverse panel of biomarkers across multiple organ systems to asses their health.

This included variables that reflect state and performance in things like pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function. For example, things that are generally known to deprecate with advancing age — measurables like leukocyte telomere length, creatinine clearance, and high density lipoprotein cholesterol. The researchers were not as interested in looking at already aged people as they were in looking at actively aging folks, so they assessed their subjects at age 26, 32, and 38.

One particularly useful aging algorithm that has emerged is the 10-biomarker National Health and Nutrition Survey (NHANES) measure of biological age. In one study with almost 10,000 participants, it was found that biological age outperformed chronological age in predicting mortality over a two-decade follow-up. But predicting mortality is something altogether different from being able to tell someone who walks into the hospital how old they are. In the absence of any ability to that, how much trust can an individual actually put in any group-derived algorithm?

One other thing the researchers considered, was assessing high resolution 2D photographs of the retina. The idea is that the condition of the small blood vessels there are a proxy for the integrity of the microvasculature of the brain, and therefore presumably of our ability to continue to do well on fine motor control or memory tasks. The metric used here is that narrower arterioles are associated with stroke risk, while wider venules are associated with hypoxia and dementia risk.

Perhaps a more fundamental indicator of aging can be gained by looking a little deeper into cell, into the primal sources of power for everything they do. In other words, coming up with a reliable indicator of the general status of mitochondria. Although this is a relatively new field of inquiry for aging, a few things have emerged. For one, their role in the metabolic reprogramming that has been associated with cancer is now coming to the fore. Although the use of mitochondrial DNA as a mutational clock on evolutionary scales has a long history, the technique is not without its pitfalls. Coming up with similar clocks for the timescale of a single organism may be even more challenging.

However, with the powerful new genetic sequencing capabilities that are now available to just about anyone enterprising enough to try them, it is just about practical to start looking for mutations on a regular basis in various kinds of cells in the body. The mitochondria arguably deliver the most important 16,000 base pair sequence in the cell, and they do it at a high level of redundancy. Compared to the much larger nuclear sequence, it may be a no-brainer to check the mitochondria inside various kinds of circulating blood cells first.

In looking across the range of primate sense and sensibilities, standard metrics of aging are not always as constant as we might at first presume. For example, the grey hair of the silver fox business exec might reflect acquired wisdom, but it would hardly intimidate on an NBA basketball court. On the other hand the grey hair of a silverback male gorilla reflects the apex of of physical prowess. In the same way baldness, is in many taken as a reliable harbinger of aging. Yet when coupled with ample facial hair, a thick short neck, and perhaps a few tattoos, the same baldness can also say ‘I’m a tough guy’ in a way little else can.