Is biologic aging more accurate than chronologic aging?
A number of newer tests available online allow a person to get an estimation of their “biologic” aging (TruDiagnostic, Generation Lab, and MyAgingTests), ranging in price from $300 to over $1,600! The basis for many of these “biologic” aging tests hinges upon presumed changes in epigenetic markers that are thought to occur over the life of an individual. A really excellent review article published in Nature by Horvath and Raj provides a thorough overview of the evidence behind DNA methylation (called “DNAm”) based biomarkers and the epigenetic clock theory of aging. As an example, the addition of a methyl group (CH3) to parts of your DNA can “silence” the area so it is no longer active (“silences” the genes), one of the primary and most well-studied epigenetic mechanisms, and the pattern of methylation can shift with age.
The assumption of these tests of biologic aging is that there are common epigenetic patterns that occur over time and can therefore be a better predictor of cellular aging than simply measuring the number of years a person has existed on Earth (chronologic aging).
While this sounds very interesting, and perhaps even promising, there are a number of potential pitfalls with this approach to measuring age:
An excellent and very thought provoking article just published in the journal Science analyzed gene expression patterns in 335 female twins (could you get a better control group in terms of DNA and age match??!), measuring 5061 genes and 181 metabolites using whole-blood RNA sequencing and serum metabolomic profiling at three or more time points over 8 years. What the researchers found was that gene and metabolite expression changed over time and was affected by both intrinsic factors (host genetics and cell type), as well as external factors (circadian timing, seasonality, and environmental exposures). This variability would most certainly call into question the accuracy of epigenetic markers as somehow representing a definitive, time-stamped, linear progression of cellular aging for a single individual when collected from their blood or saliva at a specific point in their life.
While gene silencing (increased DNA methylation) is certainly a part of the differentiation of cells, there is often a progressive loss of gene silencing in aging cells. An excellent review article about this “heterochromatin loss model of aging” highlights that, “…age-related dysregulation of chromatin organization can lead to cellular malfunctions and exacerbate the aging process.” This important finding highlights the importance of knowing which genes are getting more silenced as we age vs. those that are getting less silenced, and comparing the two over the lifespan.
The American Medical Association Journal of Ethics has expressed significant concerns about these direct-to-consumer biologic aging tests: “Experts outside of the commercial venture are prevented from impartially analyzing the algorithms via a peer-review process, and other independent developers are not allowed to dig into the code to check for flaws and biases. Not only does this secrecy make monopolies more likely and innovation less likely, but many potential users will also find it difficult to trust a technology that is largely protected from public scrutiny, and rightly so. The lack of transparency makes it easier for commercial companies offering epigenetic testing to manipulate the results and provide false positives to sell products that might or might not work.”
Hopefully, with greater research, transparency, and knowledge distribution, we can generate models that accurately reflect the true aging process within the human body. Extensive research has shown that modifications in our lifestyle can impact aging biomarkers through epigenetic modifications, so it would be very useful indeed to determine whether we are besting our age in years by monitoring those markers. As physicians, we often see individuals of the same chronologic age demonstrating very different “phenotypic” age, so understanding the many variables affecting these variations in human health and wellbeing is absolutely essential. I explore the epigenetic impacts of many lifestyle factors, in detail, in my book Optimized. Check it out.
