Why do some people stay healthy throughout their lives and others don’t?
While we all age, we don’t all age in the same ways or at the same rate. Epigenetic modifications are largely responsible for this phenomenon, with DNA methylation being the most studied modification.
An Epigenetic Clock is a sophisticated way of tracking our “real” age by measuring methylation or demethylation at particular DNA sites (Kanherkar, 2014). The uses for epigenetic clocks are manifold. The most obvious use comes as a diagnostic tool, one that is already being offered by some companies as a direct-to-consumer test. The second is as an in vitro screening method, something to inspect the effects of pharmaceuticals on cells in a petri dish. This lets researchers analyze subtle molecular signs of aging, paving the way for the rapid discovery of potential anti-aging therapeutics (Lujan, 2019).
“In geriatric medicine, we are always struck by the difference between our patients’ chronological age and how old they appear physiologically.”- Douglas, Kiel, HMS professor of medicine at Beth Israel
Accurately estimating biological age has tremendous value. This is because aging has a negative effect on every aspect of our health. It’s not a substitute for more specific tests, like fasting glucose levels, but paints a big picture. Like any other biomarker, it does not stand alone, but it is complementary to the growing ensemble of tests modern medicine now has at its disposal. Epigenetic clocks made headlines with the publication of a paper that found all-cause mortality could be predicted based on methylation patterns in blood (Marioni et. al, 2015).
In other words, the team found they could guess when someone was going to die from any number of natural causes.
However, the title of MIT’s article, Want to know when you’re going to die? is sensationalistic and misleading. Even if our initial reading is not spectacular, we can take steps to change it. Some epigenetic modifications are well-entrenched, but not all are set in stone (Kanherkar, 2014). The sands of time flow downwards for us all, but the pace varies. In other words, what is not completely reversible can still be influenced by our choices, if not through lifestyle changes, then through future therapeutics meant to produce specific changes in the epigenome.
While the usefulness of epigenetic clocks is not questioned, it is not clear why they work. It’s also not obvious as to whether changes in DNA methylation are the cause or result of aging (Eckler, 2019). Despite this fact, the literature about their current and potential applications continues to grow. A deeper understanding of exactly what’s going on behind the scenes will help us develop more precise therapeutics. Steve Horvath, a pioneer in the field, envisions a future where you can go to your doctor, get your clock checked, get a prescription, then return a few months later, significantly “younger” than before.
Smoking, drinking, stress, chronic infection, and major depression can all measurably accelerate the aging process as gauged by the epigenetic clock (Gao, 2016; Gassen, 2017; Horvath, 2015; Rosen, 2018; Han, 2018). There is also an intrinsic rate of aging, which appears to vary between individuals and populations. Certain groups, like the Tsimane of Bolivia, age slowly compared to other ethnicities (Horvath, 2016).
Direct-to-consumer kits are proliferating, like BioViva’s TimeKeeper™ and Elysium’s Index. Discouraging readings shouldn’t be cause for panic or despair, but they can serve as wake up calls. A bad reading can be a cause for further investigation – maybe it’s an issue with your telomeres or mitochondria. Maybe it’s a Klotho deficiency.
Whether it’s prognostics, diagnostics, precision medicine, drug discovery, or basic research in gerontology, there is no doubt that the use of and uses for epigenetic clocks will continue to explode.
References and Works Cited
Horvath S, et al. (2018). “Epigenetic Clock Can Calculate Biological Age, Predict Lifespan.” Medical News Today, MediLexicon International.
Ecker S, Beck S. (2019). “The epigenetic clock: a molecular crystal ball for human aging?.” Aging (Albany NY) 11 (2): 833-835.
Han, Laura KM, et al. (2018). “Epigenetic aging in major depressive disorder.” American Journal of Psychiatry 175. (8). 774-782.
Horvath S, Raj K. (2018) “DNA methylation-based biomarkers and the epigenetic clock theory of ageing.” Nature Reviews Genetics. 19.371-384.
Horvath S et al. (2016). “An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease.” Genome biology 17 (1) 171.
Horvath S, Levine AJ. “HIV-1 infection accelerates age according to the epigenetic clock.” J Infect Dis. 212(10):1563‐1573.
Kanherkar RR, Bhatia-Dey N, Csoka AB. (2014). “Epigenetics across the human lifespan.” Front Cell Dev Biol 2. 49.
Lujan C, Tyler EJ, Ecker S, et al. (2019). “A CellAge epigenetic clock for expedited discovery of anti-ageing compounds in vitro.” bioRxiv.
Marioni RE, Shah S, McRae AF, et al. (2015). “DNA methylation age of blood predicts all-cause mortality in later life.” Genome Biol. 16(1): 25.
Weintraub, Karen. “Want to Know When You’re Going to Die?” MIT Technology Review, MIT Technology Review, 2 Apr. 2020. Web.