Philosophers have been debating the concepts of fate and free will for thousands of years, arguing whether we have agency over our own outcomes or are fated to fulfill our destiny—but, fortunately, the answer is much clearer when it comes to our biology. Despite everything we might hear about inherited risks and genetic dispositions, our bodies are not Greek tragedies that doom us to inevitable developments of obesity, type 2 diabetes or heart disease.

In fact, our inherited genes have—at best—only around 5 to 10 percent to do with our risk of developing the vast majority of diseases such as cancer, diabetes and Alzheimer’s [1].

What great news this is being that much of the control over our health is in our hands. At the minimum, 90 percent of our health and potential for longevity results not from our inherited genetics but from our epigenetics, the modifiable behaviors and environments that determine how our genes are expressed.

A brief history of epigenetics

Our genes are fixed. We inherit them from our parents and can’t change them (at least, not without gene editing technologies like CRISPR, which are on the horizon but still in clinical trials). But there’s something more powerful—and, crucially, more modifiable—than our genes. That’s our epigenetics, which literally means “above genetics.”

The term was first coined in 1942 by Conrad Waddington, a British biologist who discovered the existence of mechanisms that preside “above” our genes to determine the path of our genetic outcomes [2]. Essentially, he found that there were “forks” or decisions in our hardwired genetic coding that allowed for different biological paths: a plasticity that allowed individual genes to follow a different set of blueprints.

His landmark discovery was that he could alter the thorax and wing structures of fruit flies by modifying the environmental temperature and chemical stimuli they were exposed to as embryos. Instead of selectively breeding flies to control the genes they inherited from their parents, as Darwin might have done, Waddington instead controlled how the genes acted, i.e., whether they were expressed or not. The physical traits these flies went on to develop in adulthood, then weren’t predetermined by inheritance but driven by modifications to the flies’ environments [3].

So, Waddington essentially discovered that our genes, though hardwired and inherited, don’t represent our predetermined fate. Rather, they give us “forks in the road” or different paths we can take depending on inputs from our behaviours and environment.

He used the metaphor of forks, but we think of our genes as keys on a keyboard because they’re a lot more complex. Like the keys on a keyboard, our genes are fixed hardware. But our epigenetics is the software that determines the coding: the decisions that determine how these keys are expressed. The same physical keyboard can therefore have very different outcomes as the outcome isn’t determined by the hardware (our genes) but by the software (our epigenetic inputs).

We might not be able to grow wings like Waddington’s fruit flies, but we can activate the genes that keep us healthy and silence the genes that make us sick through a process called DNA methylation.

Expressing genes

If we think of our genes as a keyboard and our epigenetics as the environmental and behavioral cues that determine our story, we can think of DNA methylation as the process behind each actual keystroke.

DNA methylation literally controls the function of our DNA by telling our body to either activate or silence a gene. It works by adding or removing methyl groups (CH3) that wrap around our DNA. Add a methyl group, and the genes are silenced or turned off. Remove a methyl group, and the genes are activated or turned on [4].

This process is highly influenced by our diet, exercise patterns, stress levels, relationships, sleep patterns, nutritional status and just about everything washing over us as we live our lives (collectively referred to as the epigenome, the chemical changes that happen to our DNA, expressing it not expressing a gene as the result of external influences). Even cuddling impacts our DNA methylation! Studies have found that infants who don’t get enough love and affection are associated with higher methylation in regions of the DNA that correspond to brain development, resulting in vulnerable brain structures associated with cognition and psychiatric symptoms [5,6].

Like hard genes, these epigenetic influences can also be “softly” inherited and passed down over generations [3]. For example, children whose parents have experienced acute or chronic stress can literally inherit their parents’ emotional trauma. Descendants of Holocaust survivors have inherited increased methylation in gene segments related to cortisol, resulting in increased vulnerability to stress and similar findings appear in children whose mothers were pregnant during 9/11 [7].

Other epigenetic changes can be made through a process called histone modification. Histones are the structural proteins that give chromosomes their shape; our DNA literally wraps around them. However, when our histones and DNA are packed too tightly, it can obscure our genes from being read and silenced. Think of a fist tightly closed around a folded piece of paper—you can’t see in to read the paper. Yet, similar to DNA methylation, adding and removing certain chemical groups can change how tightly our DNA and histones are packed, expressing or silencing genes by providing access to read them.

Activating longevity pathways

Both DNA methylation and histone modification can be positively influenced at any stage of our lives. This is great news because it means we can modify our gene expression—which genes get expressed —and control the keystrokes that determine the story of our health. The key is learning what optimises our gene expression for health and longevity and what shuts down disease. For example, you want the genes for inflammation turned off and the genes that suppress tumors turned on.

We’ve long known that exercise has physical benefits that significantly reduce our risk of disease—but it turns out that it also has epigenetic benefits!

In fact, just a single bout of exercise can increase the gene expression of SIRT1, a longevity gene that protects cells against oxidative stress, regulates glucose and lipid metabolism, reduces inflammation and promotes healthy aging. You read that right: exercising just one time can literally modify the expression of our inherited genes. That said, repeated exercise compounds this effect [8,9]. Factors as simple as taking the right vitamins or eating fresh fruits and vegetables can have similar impacts. For example, studies show that deficiencies in folate, vitamin B6 and vitamin B12 can impede DNA methylation, which has been linked to the development of certain cancers, cognitive impairment, and Alzheimer’s disease [10-12].

Here are some simple steps you can take to upgrade your biological software:

Eat for your genes:

Increasing your intake of specific nutrients and bioactive food compounds can positively influence the expression of genes involved in metabolism, disease prevention, and overall health.
– Focus on phytochemicals by eating foods rich in sulforaphane (found in cruciferous vegetables like broccoli), fisetin (found in strawberries, apples, and persimmons) and catechins (found in green tea)
– Boost your methylation vitamins (B12, B6, folate) with foods such as meat, fish, leafy greens, lentils, nuts, liver and sunflower seeds
Supplement for your epigenome
Getting all your nutrients and phytochemicals from diet alone can be difficult, even with the perfect diet, so consider supplementing to fill in any nutritional gaps.
– Take a B complex or methylation cocktail (specifically looking for methyl-folate, methyl B12 and the methylated form of B6, pyridoxal-5-phosphate to support methylation)

Avoid environmental toxins

Exposure to environmental toxins can influence the patterns of DNA methylation, potentially leading to abnormal gene expression, which impacts various biological processes and has been linked to diseases such as cancer.

– Eliminate plastics, pesticides, herbicides, phthalates, PFAS chemicals, and heavy metals from your environment. Check out www.ewg.org for guides on how to reduce toxins in food, household cleaning products and skincare products.

– Consider a water filter and an air filter to address water contaminants and air pollution at home.

Our tips for detoxifying your life in Amsterdam you can find here.

Increase your exercise intake

Introducing the body to good stress through physical exercise increases NAD, which activates sirtuins and helps repair DNA and improve epigenetic expression.
– Aim for a foundation of 150 minutes per week of a combination of cardio and strength training practices such as jogging, biking, tennis, dancing, rowing, weightlifting, resistance bands and bodyweight exercises
– Consider adding yoga practice, which has been shown to influence gene expression and epigenetic modifications such as down-regulating inflammatory cytokines and enhancing the expression of genes involved in energy metabolism [13]

Address stress and engage in active relaxation

Reducing stress has been associated with dramatic reductions in disease and increased longevity and addressing the connection between mind and body plays a key role in optimising our genetic expression and biological functions.
– Supplement with magnesium, a relaxation mineral involved in hundreds of enzymatic reactions, including many involved in DNA replication, repair and transcription (magnesium glycinate) is highly bioavailable and supports sleep and relaxation in addition to many other benefits)
– Make time for mindfulness by prioritising relationships and practicing activities such as meditation and activities that calm you (drawing, puzzles, journaling), which has been shown to reduce biomarkers associated with inflammation [14].

In summary, the impact of this on longevity can’t be overstated. Our genes have put the control of our health in our hands. Something as simple as going for a long walk or eating broccoli can literally alter the expression of our genes—and, in doing so, allow us to rewrite the story of our own health.

References

1. Patron J, Serra-Cayuela A, Han B, Li C, Wishart DS. Assessing the performance of genome-wide association studies for predicting disease risk. PLoS One. 2019;14(12):e0220215. Published 2019 Dec 5. doi:10.1371/journal.pone.0220215
   
   2. Saavedra LPJ, Piovan S, Moreira VM, et al. Epigenetic programming for obesity and noncommunicable disease: From womb to tomb. Rev Endocr Metab Disord. Published online December 2, 2023. doi:10.1007/s11154-023-09854-w
   
   3. Denis Noble; Conrad Waddington and the origin of epigenetics. J Exp Biol 15 March 2015; 218 (6): 816–818. doi: https://doi.org/10.1242/jeb.120071
   
   4. Gujral, P., Mahajan, V., Lissaman, A.C. et al. Histone acetylation and the role of histone deacetylases in normal cyclic endometrium. Reprod Biol Endocrinol 18, 84 (2020). https://doi.org/10.1186/s12958-020-00637-5
   
   5. Moore SR, McEwen LM, Quirt J, Morin A, Mah SM, Barr RG, Boyce WT, Kobor MS. Epigenetic correlates of neonatal contact in humans. Dev Psychopathol. 2017 Dec;29(5):1517-1538. doi: 10.1017/S0954579417001213. PMID: 29162165.
   
   6. Fujisawa TX, Nishitani S, Takiguchi S, Shimada K, Smith AK, Tomoda A. Oxytocin receptor DNA methylation and alterations of brain volumes in maltreated children. Neuropsychopharmacology. 2019 Nov;44(12):2045-2053. doi: 10.1038/s41386-019-0414-8. Epub 2019 May 9. PMID: 31071720; PMCID: PMC6898679.
   
   7. Dashorst P, Mooren TM, Kleber RJ, de Jong PJ, Huntjens RJC. Intergenerational consequences of the Holocaust on offspring mental health: a systematic review of associated factors and mechanisms. Eur J Psychotraumatol. 2019;10(1):1654065. Published 2019 Aug 30.doi:10.1080/20008198.2019.1654065
   
   8. Kilic U, Gok O, Erenberk U, Dundaroz MR, Torun E, et al. (2015) A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human. PLOS ONE 10(3): e0117954. https://doi.org/10.1371/journal.pone.0117954
   
   9. Juan, C.G., Matchett, K.B. & Davison, G.W. A systematic review and meta-analysis of the SIRT1 response to exercise. Sci Rep 13, 14752 (2023). https://doi.org/10.1038/s41598-023-38843-x
   
   10. Tiffon C. The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease. Int J Mol Sci. 2018;19(11):3425. Published 2018 Nov 1. doi:10.3390/ijms19113425
   
   11. Agarwal D, Kumari R, Ilyas A, Tyagi S, Kumar R, Poddar NK. Crosstalk between epigenetics and mTOR as a gateway to new insights in pathophysiology and treatment of Alzheimer’s disease. Int J Biol Macromol. 2021;192:895-903. doi:10.1016/j.ijbiomac.2021.10.026
   
   12. An, Y., Feng, L., Zhang, X. et al. Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1. Clin Epigenet 11, 139 (2019). https://doi.org/10.1186/s13148-019-0741-y

13. Giridharan S. Beyond the Mat: Exploring the Potential Clinical Benefits of Yoga on Epigenetics and Gene Expression: A Narrative Review of the Current Scientific Evidence. Int J Yoga. 2023;16(2):64-71. doi:10.4103/ijoy.ijoy_141_23 

14. Redwine LS, Henry BL, Pung MA, et al. Pilot Randomized Study of a Gratitude Journaling Intervention on Heart Rate Variability and Inflammatory Biomarkers in Patients With Stage B Heart Failure. Psychosom Med. 2016;78(6):667-676. doi:10.1097/PSY.0000000000000316