As stated in the previous article, epigenetic alterations are the key hallmark of aging. Indeed, multiple studies point to the fact that dysregulation of epigenetic mechanisms induces changes of gene expression that underlie the aging process in different tissues. These epigenetic mechanisms are: DNA methylation, histone acetylation and non-coding RNAs.

Dr. David Sinclair, Professor of Genetics at Harvard Medical School, claims in his acclaimed book, “Lifespan: Why We Age and Why We Don´t Have To”, that “epigenetic drift/noise, which are alterations to the epigenome [1] that take place with age due to changes in methylation, often related to an individual´s exposure to environmental factors, may be a key driver of aging in all species” [2].

In this article, we will explore the factors that affect these epigenetic alterations and that hence contribute to epigenetic “drift/noise”. Various factors are being shown to impact the aforementioned epigenetic mechanisms, such as: nutrition, smoking, alcohol consumption and physical activity.

There is emerging evidence that physical activity can regulate epigenetic mechanisms, many of which are associated with an array of human diseases. Summatively, and without getting into complex molecular mechanisms, a study conducted by Graziolo et al. found that moderate physical activity has the capacity to preserve and/or recover “positive” epigenetic markers that are known to be modified in important chronic diseases, including cardiovascular and neurodegenerative diseases. [3]

With regards to alcohol consumption, Van Engeland et al postulate that alcohol intake was associated with changes in methylation of tumour suppressor and DNA repair genes in colorectal cancer tissues [4]. Overall, exposure to alcohol has been shown to alter gene expression through epigenetic mechanisms.  The alcohol-mediated chromatin remodelling in the brain promotes the transition from use to abuse and addiction [5].

Moving on to nutrition, there are a number of natural compounds that have been shown to affect (positively and negatively) epigenetic alterations. On one hand, compounds such as polyphenols (found in foods such as berries, herbs and spices, tea, vegetables, nuts and soybeans) have  been shown to reverse in-vitro models some of the epigenetic aberrations associated with malignant transformation.[6] On the other hand, a Western Diet (which tends to be high in saturated fats, red meats, simple carbohydrates and low in fruits and vegetables, whole grains, etc.) has a well-established negative impact on the human body, and epigenetics, such as DNA methylation, may play a role in this process.[7]

Lastly, cigarette smoking is considered one of the most powerful environmental modifiers of DNA methylation.[1] As you´ll recall, DNA methylation is one of the key epigenetic mechanisms. Cigarette smoke induces DNA double-strand breaks, which causes recruitment of DNA methyltransferases (the enzymes that catalyze DNA methylation) and thus contributes to epigenetic drift/noise. Furthermore, according to Zong et al.  transcription regulation by NF–κB, a key pro-inflammatory molecule, appears to have a main function in cigarette smoking-induced epigenetic changes in the mediation of inflammation.

We can hence conclude that all forms of toxicity, including smoking, diet and heavy metals, alcohol consumption, etc. trigger epigenetic alterations that contribute to the so-called epigenetic noise, as coined by Dr. David Sinclair. This in turn, as we discussed previously, is the crucial hallmark of aging.

The combined epigenetic noise in our bodies generate chronic inflammation and cellular ageing. At Longevity, we provide various personalised, preventive, integrative and regenerative medical wellness solutions to combat these negative effects.

[1] Refers to changes to a cell´s gene expression that do not involve altering its DNA code. Sinclair, D. and LaPlante, M.D. (2021) Lifespan: Why we age and why we don’t have to. London: Harper Thorsons.

[2] Sinclair, D. and LaPlante, M.D. (2021) Lifespan: Why we age and why we don’t have to. London: Harper Thorsons.

[3] https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-4193-5

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752894/

[5] https://pubmed.ncbi.nlm.nih.gov/30412425/

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752894/

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275017/

[8] https://www.frontiersin.org/articles/10.3389/fgene.2013.00132/full

It is common to hear that we all age and that aging is a natural and even inevitable process, that it is a physiological process intrinsically linked to the human (and animal) condition. However, to what extent is this statement fully accurate? In the late 2000s, scientists came up with a tentative hypothesis for the causes, or hallmarks, of aging. These hallmarks are arranged into a “pizza”, whereby each hallmark represents a slice which has an equal weighting, as seen in the image below.

[1] Aging Hallmarks

So, according to López-Otin et al [2], the nine conjectural hallmarks of aging, in different organisms, are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

Notwithstanding, more recently, Dr. David Sinclair, Professor of Genetics at Harvard Medical School, one of Time´s most influential figure and a prominent figure in the field of research related to aging, argues that there is one hallmark of aging which predominates over the others: epigenetic alterations. That is, aging is a loss of epigenetic information, which are the control systems which regulate which genes are expressed and which ones are supressed at a certain time in a cell.

Additionally, Dr. Sinclair claims that the other hallmarks of aging, mentioned above, are largely manifestations of this major hallmark (epigenetic alterations). Thus, we will now talk about some of the main causes of epigenetic alterations in the human genome which contribute to and accelerate aging.

Smoking is one of the main causes of epigenetic instability, as it exhausts the DNA repair systems which are recruited due to the DNA damage induced by smoking. Other major causes of epigenetic alterations include: N-nitroso compounds, which are found in many red meats and bacon (these compounds are powerful carcinogens) and exposure to radiation (including X-rays and gamma rays). In other words, the environment (that is, exposure to radiation and different forms of toxicity) and lifestyle (namely diet, exercise and stress), in all its dimensions, both contribute to a greater amount of epigenetic alterations, which in turn intensify the aging process.

To conclude, there are nine major hallmarks which underpin the aging process. However, the key hallmark which appears to trigger the other hallmarks is epigenetic alterations. In the next articles, we will elaborate on the topic of epigenetic alterations, the factors that accelerate it and how to minimise its impacts.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/

Aging is a natural and unavoidable process which starts at birth. Wrinkled skin, greying and thinning hair, loss of muscle strength and tone, joint pain, fatigue, memory loss, and disease are common signs of aging. These phenomena also imply loss of functionality and adaptability. Both life span and quality of life become important factors in longevity considerations: not just living long but aging well in the years we are alive.

We know the secrets to longevity and wellbeing: exercise, no smoking, less stress, enough sleep, active lifestyle, work-life balance, healthy diet, low sugar, correct posture, proper breathing, mindfulness, and a positive mindset. Finding purpose, feeling gratitude and being of service to others also enhance the quality and meaning of life.

Science offers two basic theories to explain aging.  Genetic theories propose that our genes are programmed to determine how we will age and that genetic encoding is responsible for about 30 percent of our lifespan. Cell death and their inability to divide properly over time is what eventually lead us to our death. If we can control our genes we can change how long we will live. These programming theories point to shortening of telomeres, a factor that impacts the ability of the cell to divide and copy DNA information. Telomeres are the caps of chromosomes, the twisted threadlike structures within the cells that store DNA information.

On the other hand, damage theories indicate that over time our bodies and DNA get damaged to the point that we are unable to function. Damage factors include attacks from the environment or within our body’s own chemical effects which result in cellular damage that is eventually irreversible. According to this perspective, the major cause of aging is “oxidative stress”, which damage DNA, proteins and fats caused by “oxidants”, resulting from breathing, inflammation, infection or consumption of cigarettes and alcohol. Neutralizing these oxidants and the free radicals they produce, could potentially increase our life span.

Aging is perhaps a result of the combination of all these factors and different theories can offer plausible explanations on how and why we age. We have been able to greatly expand life expectancy in the last few hundred years and we may continue to be successful in years to come. Regardless of the underlying factors of aging and dying and until science finds the immortality secret, there seems to be agreement on a key component in minimizing DNA damage in our bodies: caloric restriction. It reduces cell metabolism and free radical production, in addition to other benefits, which are certain to enhance health, promote longevity by delaying aging.