Chapter 175
Changing Aging — 12
We’re at a time when thousands of plasma proteins can be assayed in thousands of people at different ages, enabling proteomic clocks and, as we’ll get into momentarily, organ clocks. When this was done to elucidate the aging proteome, three distinct peaks were found (fig. 12.3) across the human lifespan, each with different sets of proteins. The second peak at middle age was predictive of cardiovascular disease and Alzheimer’s. I think of Ernest Hemingway’s character Mike’s line in response to how he went bankrupt in The Sun Also Rises: “Gradually, then suddenly.” Aging proteins in contrast speed up and slow down at certain points. These clocks may be providing the vital warning signs to head off the later, sudden demise.
But do these biologic omic clocks, beyond the second-generation epigenetic clocks, provide unique or complementary information about the aging process? That’s uncertain. A study that assessed genomics, proteomics, and metabolomics, but not epigenetics, in more than thirty-five hundred individuals missed the opportunity to shed light on this uncertainty. The various clocks have been developed from populations and have questionable relevance and specificity at the individual level. Beyond these unknowns, we really don’t know what “biological age” means, especially for a given individual. While it’s gratifying to get a report that your biological age is ten years younger than your chronological age, it doesn’t have adequate anchoring from prospective clinical trials. For example, if the biologic age was accurately determined for a person to be several years greater than the chronological age, would knowledge of the clock result change lifestyle factors that have been associated with improvement? Or shouldn’t that person be adapting the healthiest known lifestyle factors anyway? Curiosity is one thing, but right now all we have to offer are the lifestyle+ factors reviewed in chapter 3.
Figure 12.3. The three distinct plasma protein peaks across the human lifespan. Adapted from Valur Emilsson et al., “Predicting health and life span with the deep plasma proteome,” Nature Medicine 25, no. 12 (December 2019): 1815–16, https://doi.org/10.1038/s41591-019-0677-y.
That hasn’t held back commercial offering for aging clocks, such as the TruDiagnostic that provides the DunedinPACE result and metrics for immune cell function, “fitness,” telomere length, and other reports; GlycanAge ($348 for one test, $599 for two); Generation Lab (four biological age tests for $149 per month and a VIP program for $3,499 per year). Companies including Tally Health, Elysium Health, and Novos Labs offer aging clocks and supplements to pair with them. I don’t recommend any of these tests (or supplements), including telomere length and epigenetic clocks. They are useful in research studies, but there is lack of clinical validation from rigorous randomized trials that having some body clock information leads to improvement in metrics or health outcomes.