Age may not be just a number when it comes to cancer

Posted by ap507 at Jun 20, 2016 11:05 AM |
The biggest risk factor for cancer is perhaps the one thing we cannot control – age, says PhD student Mohan Harihar

Think: Leicester does not necessarily reflect the views of the University of Leicester - it expresses the independent views and opinions of the academic who has authored the piece. If you do not agree with the opinions expressed, and you are a doctoral student/academic at the University of Leicester, you may write a counter opinion for Think: Leicester and send to ap507@le.ac.uk  

There are many who would say that cancer is a modern, man-made phenomenon brought about through the exposures and indulgences available to us all on a day-to-day basis. Smoking, drinking, exposure to radiation and the cancer risk associated with excessive consumption of red/processed meat are among the examples of environmental factors typically associated with an increased risk of cancer (specifically ‘non-inherited’ or ‘sporadic’ cancers).

Interestingly, the definition of ‘cancer’ seems to have changed over the years which can be attributed to the changing attitudes towards what causes cancer – achieved largely through the vast pool of research which has been published in the last 20 years or so.

But is the biggest risk factor for non-inherited cancers one thing we have no control over?

Aging is a natural process which we all go through regardless of the cosmetic procedures and products we may choose to take advantage of. Whilst a number of degenerative consequences of aging can include benign to mild conditions, such as hair loss, skin wrinkling and deteriorating vision, in some cases the onset of more serious diseases becomes more probable – such as heart problems and neurodegenerative disorders. 

Cancer is perhaps one such example of a serious consequence of aging where degeneration occurs at the biochemical level.

Interestingly mid-life appears to be a transition point where the number of occurrences of such diseases, including cancer, rises almost exponentially.

Cancer Research UK (CRUK) reported that between 2011-13, 50% of cancer cases were in people aged 70 and above. Similar figures can be observed across multiple countries.

So why is this the case?

In the context of biochemistry, cellular aging can encompass a variety of processes and changes to cells which can impact the ‘microenvironment’ they reside in.

General DNA damage

We all endure thousands of naturally occurring errors and mutations in our DNA every day. More often than not these are repaired by so-called ‘caretaker genes’.

It seems reasonable to suggest a person who lives to a greater age may over time accumulate unrepaired DNA damage which increases the likelihood of a critical cancer-promoting gene being affected.

Of course the frequency of these mutations can be increased by a number of environmental factors as mentioned previously.

It is important however to state that those who live to a greater age leading ‘less healthy’ lifestyles are theoretically at a higher risk of developing cancers than a ‘healthy’ individual of the same age.

Nonetheless DNA damage and modifications will always occur which in some cases can evade repair and, coupled with a deteriorating immune system as one ages, can lay the foundation for tumour development. In fact according to CRUK, only 4 in 10 cancers each year are linked to major lifestyle factors, suggesting the remaining six develop in a more ‘natural’ manner.

The presence and accumulation of ‘senescent cells’

senescentcells.jpg
Senescent cells
Another concept which may help explain the link between age and cancer development is that of ‘senescence’ or ‘replicative senescence’, the natural process by which cells stop dividing once they have reached their ‘Hayflick Limit’ (the maximum number of times a cell is able to divide).

Whilst the presence of seemingly inactive cells sounds harmless, senescent cells are known to still release a variety of molecules – some of which can promote inflammation.  This characteristic showcased by senescent cells is known as the ‘senescence-associated secretory phenotype’ (SASP).

A number of studies have demonstrated that a number of these released SASP molecules can in fact promote tumour growth (presumably the molecules which promote inflammation – one of the ‘enabling characteristics’ described by Robert Weinberg and Douglas Hanahan in 2011).

For example, in mouse models injection of senescent cells have been shown to promote growth of tumour cells. SASP factors have also been revealed to facilitate cell motility - a trait invasive cancer cells display. This is embodied by a process termed the ‘epithelial-to-mesenchymal transition’ (EMT) which is a well-studied phenomenon outlining how static cells become mobile.

Alarmingly the SASP molecules secreted by senescent cells have even been shown to confer a protective property and resistance against chemotherapy to neighbouring tumour cells.

These are just a few examples of the tumour-promoting effects of SASP molecules.

This would suggest that even senescent cells, though not replicating, still possess enough biochemical activity to influence nearby replicative cells. The danger lies in these senescent cells not actually being killed off. The population of senescent cells can increase over time leading to a highly tumour-promoting microenvironment.

The emerging field of epigenetics with respect to cancer

Another interesting link to age-associated cancer risk looks into the field of ‘epigenetics’, which is the study of gene expression changes as a result of external/environmental factors alone and not modifications to the principal underlying genetic code. It has been noted that centenarians exhibit delayed age-associated methylation alterations (a biochemical process in which chemical

DNA methylation
molecules known as ‘methyl’ groups are tagged onto DNA which can modulate gene expression patterns). Moreover this characteristic can be passed on to their children.

It will be interesting to observe in the future whether individuals who demonstrate delayed methylation have consistently higher cancer risks/incidences than those with normal methylation patterns.

Are our more efficient and effective healthcare systems contributing to an increased cancer risk?

One thought-provoking issue which comes out of all this is one which appears paradoxical.

As is known, the ever-improving healthcare system, medicine and technology are allowing more people to fight and beat a plethora of diseases than ever before – ranging from a simple flu to cardiovascular disease. However, by achieving this, are we also being put at a greater risk of developing cancer by having our lives prolonged?

Another CRUK statistic states that 1 in 2 people born after the year 1960 will develop a form of cancer at some point during life. For a long time this probability was 1 in 3. This may very well be a reflection of the advancement of healthcare in the last 50 years and how more people are living longer because of this. Consequently the inherent cancer risk is likely to go up.

It seems harsh to paint healthcare in any sort of negative light but it could be argued that the gradual rise in naturally occurring cancer cases could be attributed, at least to a certain degree, to prolonging life through effective medicine.

All things considered, it is difficult to disregard the probable impact of age on increased cancer risk. As mentioned previously, mid-life is the age at which the majority of adults will experience age-related physical ailments. Though a number of these instances can be delayed or prevented through interventions that promote healthier lifestyles, it is difficult to ignore the prospect that in some way the increase in cancer risk is inevitable as one ages. 

This might mean that the phrase “age is just a number” is ill-used when it comes to cancer.

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