Why do some people stay healthy throughout their lives and others dont?
Whilewe all age, we dont all age in the same ways or at the same rate. Epigeneticmodifications are largely responsible for this phenomenon, with DNAmethylation being the most studied modification.
An EpigeneticClock is a sophisticated way of tracking our real age by measuring methylationor demethylation at particular DNA sites (Kanherkar, 2014). The uses forepigenetic clocks are manifold. The most obvious use comes as a diagnostictool, one that is already being offered by some companies as adirect-to-consumer test. The second is as an in vitro screening method, something to inspect the effects ofpharmaceuticals on cells in a petri dish. This lets researchers analyze subtlemolecular signs of aging, paving the way for the rapid discovery of potentialanti-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
Accuratelyestimating biologicalage has tremendous value. This is because aging has a negative effect onevery aspect of our health. Its not a substitute for more specific tests, likefasting glucose levels, but paints a big picture. Like any other biomarker, itdoes not stand alone, but it is complementary to the growing ensemble of testsmodern medicine now has at its disposal. Epigenetic clocks made headlines withthe publication of a paper that found all-cause mortality could be predictedbased on methylation patterns in blood (Marioni et. al, 2015).
Inother words, the team found they could guess when someone was going to die fromany number of natural causes.
However,the title of MITs article, Want to knowwhen youre going to die? is sensationalistic and misleading. Even if ourinitial reading is not spectacular, we can take steps to change it. Someepigenetic 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 otherwords, what is not completely reversible can still be influenced by ourchoices, if not through lifestyle changes, then through future therapeuticsmeant to produce specific changes in the epigenome.
Whilethe usefulness of epigenetic clocks is not questioned, it is not clear why they work. Its also not obvious asto whether changes in DNA methylation are the cause or result of aging (Eckler,2019). Despite this fact, the literatureabout their current and potential applications continues to grow. A deeperunderstanding of exactly whats going on behind the scenes will help us developmore precise therapeutics. Steve Horvath, a pioneer in the field, envisions afuture where you can go to your doctor, get your clock checked, get aprescription, then return a few months later, significantly younger thanbefore.
Smoking,drinking, stress,chronic infection, and majordepression can all measurably accelerate the aging process as gauged by theepigenetic clock (Gao, 2016; Gassen, 2017; Horvath, 2015; Rosen, 2018; Han,2018). There is also an intrinsic rate ofaging, which appears to vary between individuals and populations. Certaingroups, like the Tsimane of Bolivia, age slowly compared to other ethnicities (Horvath,2016).
Direct-to-consumerkits are proliferating, like BioVivasTimeKeeper and Elysiums Index.Discouraging readings shouldnt be cause for panic or despair, but they canserve as wake up calls. A bad reading can be a cause for further investigation maybe its an issue with your telomeres or mitochondria. Maybe its a Klothodeficiency.
Whetherits prognostics, diagnostics, precision medicine, drug discovery, or basicresearch in gerontology, there is no doubt that the use of and uses forepigenetic clocks will continue to explode.
Referencesand 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):15631573.
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 Youre Going to Die? MIT Technology Review, MIT Technology Review, 2 Apr. 2020. Web.
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Gauge Your Age: Epigenetics and the Future of Medicine - WhatIsEpigenetics.com
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