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/

In his critical book entitled “Why We Age-and Why We Don´t Have To”, a genetics professor at Harvard Medical School Dr. David Sinclair defines telomeres as a cap that protects the end of the chromosome from attrition, analogous to the aglet at the end of a shoelace or a burned end of a rope to stop it fraying.[1] It is well established that as we age, telomere length shortens. After telomeres shorten to a certain length, a cell stops dividing and becomes senescent. Consequently, telomere length is a key biomarker of ageing.

Indeed, according to Dr. Sinclair, the attrition of telomeres is one of the hallmarks of ageing and the diseases that arise as a result of it. Many research papers have pointed to lifestyle factors that can accelerate the pace at which telomeres shorten. This is good news: it means that by modifying specific aspects of lifestyles for the better, we can significantly alter the rate of telomere shortening and thus increase lifespan.

Many lifestyle factors are strongly associated with an increased pace at which telomeres shorten. One of these major factors is smoking. According to Shammas, the dose of cigarettes smoked is positively correlated with accelerated telomere shortening. The mechanism behind why smoking has this detrimental effect on telomeres is via an increase in oxidative stress. Another lifestyle factor associated with an increased rate of telomere shortening is obesity. Obesity accelerates the ageing process; indeed, the telomeres in obese women have been shown to be significantly shorter than those in lean women of the same age group.[2] Other factors which speed up the rate of telomere shortening include exposure to pollution and stress (associated with the continuous release of glucocorticoid hormones, like cortisol).

On the other hand and on a different note, several lifestyle factors seem to have protective effects on the rate of telomere shortening. For example, diet (including what, how much and when we eat) appears to have a major effect on our telomeres and therefore on our longevity and vitality. Dietary restriction in general increases lifespan and is associated with longer telomeres. Indeed, the so-called “longevity hot spots” are all places where there is a strong fasting behaviour, which triggers an increased expression of your longevity genes (i.e. increased expression of sirtuins and down-regulation of the mTOR pathway). Intake of antioxidants (e.g. vitamin C, vitamin E, beta-carotene) can prevent accelerated telomere attrition. Also, dietary intake of fibre is positively correlated with telomere length. Another major lifestyle factor which prevents telomere attrition is exercise. To put it simply, and as stated in Dr. Sinclair´s book, those who exercised more had longer telomeres.[3]

Overall, caloric restriction, exercise, ingestion of antioxidants and fibre all slow down the rate of telomere shortening. Contrastingly, smoking, obesity, exposure to pollution and stress accelerate telomere shortening and hence the ageing process.

[1] Lifespan: Why We Age – and Why We Don’t Have To. Book by David A. Sinclair PhD.

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/