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!
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Do anti-ageing diets really work?

Three years ago this month, Dr Michael Mosley demonstrated ‘the power of intermittent fasting’ on the BBC programme Horizon.  He based his argument for this regime on evidence that had been mounting for some time that calorie restriction can prolong life.

However, many scientists challenge these assumptions, partly because of a lack of consistency between the various studies on monkeys, mice, rats, and even fruit flies. A review published in 2014 recognised that calorie restriction diets might be inadvertently correcting pre-existing imbalances in nutritional intake in the laboratory animals.

A team of researcher in Sydney took a different approach. They already knew that individuals who were deficient in certain growth factors did not suffer from cancer or diabetes, both of which are associated with the ageing process. They also knew that production of these cellular growth factors required particular amino acids. As amino acids are the building blocks of protein, it made sense to explore the effects of differing amounts of protein in the human diet. They analysed the proportion of protein in people’s diets, drawing on an existing national USA dataset. They also had access to health and mortality information about the people in their sample.

The Sydney team discovered something quite remarkable. Among the age group 50-65, high animal (not plant) protein intake was associated with shorter lives. This high protein group were almost four times more likely to die from cancer, when compared with the low protein group.

For those aged 66 plus, however, the tables turned. For this older group, longevity was associated with high protein intake. Those with a high protein intake were far less likely to develop cancer than those on low protein diets.

These are early days yet, and it is likely to be some time before any clear dietary recommendations can emerge. Much of the current advice for slowing the ageing process is based on having a good intake of antioxidants, dietary fibre and omega-3 fatty acids.

Antioxidants are purported to help moderate DNA damage – genetic mutations and chromosome damage – which can build over time and gradually disable more and more cells. Dietary fibre helps to moderate things such as the sugar and fats in our blood, as well as helping to maintain a healthy bowel. Omega-3 fatty acids are ‘good’ fats, for which many unproved claims are made, and even the case for promoting heart health is debated.

Does improving health through diet increase longevity? Having healthy heart and bowels may not protect us from the inevitable march of cumulative DNA and chromosome damage. Even the link between free radicals and antioxidants may not lengthen life.

It seems we have a long way to go before we can stop ageing in its tracks, but I suspect that many of us would opt for a moderately long and healthy life rather than simply a very long life.