Is ageing inevitable?

I started writing this article when ageing was again in the news, this time in connection with shift workers. We have mounting evidence that working night shifts can accelerate ageing and decrease longevity. But what is ageing exactly? And can we protect ourselves against it?

Edward_S._Curtis_Collection_People_086

Although we can see and experience getting old as a process of ‘slowing down’, becoming forgetful, and the accumulation of skin wrinkles and grey hair, it takes study at the cellular level to appreciate what is actually happening. Studying the internal workings of cells reveals unimaginable complexity and the inevitability of the ageing process. We will be hard pushed to come up with any elixir for longevity.

‘Longevity’ simply means a long life. The longest life on record is that of a French woman Jeanne-Louise Calment (1875-1997) who lived to nearly 123 years old. The biological world describes longevity as a phenotype – a set of observable characteristics of an individual resulting from the interaction of their genes with the environment. You might ask, then, how is the interaction between genes and environment affecting our longevity and causing us to age?

Our genes are strung together on chromosomes inside each of our body’s cells. Humans have 46 chromosomes in each cell. During growth and renewal, certain cells divide to produce new cells. A lifetime average is 10 million cell divisions every second. The genetic code perpetuates by processes of chromosome replication, followed by orderly separation of the duplicates in the creation of a new cell. We tend to think that each cell division faithfully reproduces and passes on the genetic blueprint, but this is far from true.

Aneuploidy

Take aneuploidy, for example. Chromosome separation sometimes goes wrong during cell division. The result of this is that some new cells may have more than or less than 46 chromosomes. Cells can usually limp along in these cases, but they have lost their vitality – in other words, they show signs of ageing.

Mutations

Mutations are probably the genetic errors with which we are most familiar. Simply put, they are random changes occurring in the genetic code within a chromosome affecting a single gene or a larger piece of the chromosome.

Telomere shortening

Telomeres
Image of chromosome, with telomeres indicated pink

Another mechanism involved in cellular ageing is telomere shortening. Telomeres are specialised pieces of DNA that cap the ends of all chromosomes. Without a telomere, the integrity of a chromosome is severely threatened. This may result in the chromosome ends forming loops by joining together, and serious difficulty in replicating at all. Critically, each time a cell divides, the chromosomes naturally lose a fragment of telomere – they progressively shorten until they eventually reach the end of the line.

Epigenetics

Epigenetics is a fascinating topic involving the study of gene expression. Certain structures within a cell are able to ‘switch’ genes on and off. Epigenetic mechanisms are what makes different body tissues do their specialised jobs – all our body cells contain the same genes, but only some are turned on.  In a chromosome, proteins known as histones form packaging material that helps to condense over 2 metres of DNA to fit into the nucleus of each of our cells. Subtle changes in these histones can interfere with their control of gene expression.

The effects of all this interference with the expression of the genetic code in our cells accumulate over time. The structure and function of the molecules that maintain the cell deteriorate with ageing, leading to a decline in the function of the cell. As the number of declining cells increases, so our bodies age more. This fits Edward Masoro’s classic definition of ageing as deterioration with advancing age, which increases vulnerability to biological challenges and hinders an individual’s ability to survive. This interpretation of ageing is also known as senescence.

Returning to the night-shift workers, the point is made that sleep is essential for enabling our body systems to replenish themselves. Upsetting normal wake-sleep patterns seems to trigger harmful processes – perhaps we do not handle sugar, stress, or appetite quite so well, for example. Toxins might not be cleared up quite as efficiently as normal.

Whether or not we work shifts, our bodies are continually mopping up harmful chemicals and dealing with the effects of bombardment by solar and other background radiation. Harmful chemicals can be external pollutants or by-products of metabolism. The more we can do to maintain our bodies in a healthy state, the better equipped we are to fend off these threats.  In the long run, though, it seems we have little defence against advancing senescence.

I gleaned much of this information through studying a free MOOC in Futurelearn: ‘Why do we age? The molecular mechanisms of ageing’  A very steep learning curve, but well worth the effort!