Ageing Research – A promise to “cure” all communicable diseases that plague our society?

Possibly one of the most up-and-coming yet controversial areas in biomedical science is the ever-growing field of ageing research. Last week Guy Brown gave introductory lectures on this topic, which were interesting and thought-provoking, especially because I previously had not given ageing much thought (neither as a thing that would affect me personally, nor as a topic of experimentation). His opening slide included this cartoon, which I copied from here:

As with most controversial topics, the controversy starts with the definition: currently there is no all-encompassing, universally accepted definition of ageing. However, most people would agree that ageing is a process that involves “progressive physical deterioration over time” (according to Prof. Brown). Furthermore, it is generally accepted that ageing is a major risk factor for a multitude of communicable late-onset diseases such as cancer, diabetes, cardiovascular disease and neurodegenerative diseases.

Therefore, if it were possible to reduce ageing – by which I mean to increase the human health span as opposed to the average/maximum human life span – then could we be preventing these diseases? In other words, should more (financial) efforts be put towards ageing research instead of cancer research, for example? A short and fairly straightforward review (Guarente (2014)) from a proponent of ageing research gives a good, if slightly biased, introduction to the area.

Generally speaking, I would argue that there are two approaches one can take when researching the process of ageing. On the one hand, one can ask why animals (but also single-celled organisms) age, and on the other hand, one can ask how animals age.

As to the why there are a lot of theories, but the main arguments include the following (and it is worth bearing in mind that ageing does not generally occur in “the wild”, since most animals die from extrinsic causes (e.g. predation or infection) before they age):

• Mutation accumulation theory (Medawar, 1952): as we age we accumulate damage in our cells, and as long as this happens after reproduction (i.e. after selection pressure has been removed to keep our DNA healthy) then this should not adversely affect our offspring’s fitness.
• Antagonistic pleiotropy theory (Williams, 1957): this theory posits that some genes, which are beneficial early during life and may increase the chances of having healthy offspring, can have detrimental effects later in life.
• Disposable soma theory (Kirkwood, 1977): after reproduction, which is costly to the individual and uses up a lot resources, an organism is less able to repair damage.

Although these theories may seem logical to a certain extent, it can be easy to start invoking teleological arguments: maybe we age (and die) in order to make space for our children? But how would that information be encoded in our genetic material if ageing (by definition, I would say) occurs after reproduction? Would Darwin be happy with this?

I dare say he might prefer to know how we age. Again, there are a slew of theories regarding the mechanism of (cellular) ageing. Lopez-Otin et al. (2013) attempted to summarise these into nine hallmarks of ageing (in analogy to Hanahan & Weinberg (2011), who have famously done this for cancer). The mechanisms proposed include the accumulation of damage to both DNA (e.g. in the form of mutations) and proteins (e.g. they might start to form toxic aggregates), the exhaustion of stem cell self-renewal capabilities, a deregulation of nutrient sensing and cellular metabolism, as well as chronic inflammation.

You might accuse me of having a pessimistic outlook on life, but from the little I have read about the process and mechanisms of ageing and the still developing area of ageing research, it seems unlikely that vastly different diseases such as cancer and diabetes can easily be tackled from this one approach. Until now (but of course who knows what the future will bring) no treatments have unequivocally been shown to increase human health span. Possibly the most promising to date is a calorie restriction regime. To me personally, however, that seems quite unappealing – do I want to live healthily but hungrily to the age of 100, or satiated but with greater probability of dying by the age of 80?

References:

Guarente L (2014) Aging Research – Where Do We Stand and Where Are We Going? Cell 159: 15-19

Hanahan D, Weinberg RA (2011) Hallmarks of Cancer: The Next Generation. Cell 144: 646-674

Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The Hallmarks of Aging. Cell 153: 1194-1217