Chapter 3
You Are as Young as You Feel — Part 1
Every one of us carries about 2 metres of DNA in every single cell, and we have 30 trillion cells. DNA consists of 23 pairs of chromosomes, each made up of 3 billion ‘letters’ of genetic information. The Human Genome Project was set up to read all of these letters. There is no index, no annotation and no easily discernible manner in which to navigate this obscure alphabet. It took thousands of scientists all over the world working together and sharing information every time they did a study over seven years to reveal more of the letters of the alphabet. It was slow, laborious and complicated. But, after 4 billion years of evolution, one organism – us – has been able to work out its own code of instructions. This has helped greatly with not just the diagnosis of genetic disorders but also in understanding the genes that contribute to longevity. Furthermore, we now understand a lot about the switching on and off of genes and how epigenetics is controlled by health behaviours and other external factors.
To date, one of the most prominent genes discovered to influence the ageing process is the DAF2 gene. Activity of this gene – i.e., whether it is switched on or off – controls many of the important pathways which govern how cells age. Examples of the role of this gene are also evident in animals. Manipulating the gene in animals – something which is not yet appropriate in humans – allows us to study how small changes in the gene function, and thus epigenetics, affect cell ageing and lifespan.
Chapter 1: You Are as Young as You Feel
In species such as the worm, a small change in the DAF2 gene doubles lifespan. Because we share a large number of genes with the worm, this is likely to be the same for humans. DAF2 also controls insulin and growth hormone activity, both of which play key roles in the growth of all tissues and how we metabolise sugar and produce energy, both fundamental processes for survival of all cells. What’s more, people who live to 90 and over have different DAF2 genetics than those who do not live beyond 90. Diet, obesity and exercise and caloric restriction influence the DAF2 gene, which may explain why these factors slow the pace of ageing and extend lifespan. This is an open door for us to use this new information in order to have more control over ageing.
Epigenetic clocks emerged from the work of the Human Genome project and are an extension of what we know about epigenetics. When we refer to a gene being switched off or on, we are describing ‘DNA methylation’ – this is the addition of a methyl group to DNA (a methyl group is one carbon atom bonded to three hydrogen atoms). This occurs all the time throughout the body and helps to keep DNA stable. The amount of change in methylation can be used to determine tissue age. By charting this change throughout life, we have created the epigenetic clock as a measure of biological ageing. It is still a developing science and new ‘clocks’, which use different combinations of measures of methylation, continue to be discovered and tested for precision. No clock is as yet precise enough to clearly measure an individual’s biological age but we are getting closer to this degree of accuracy. Very soon, we will be able to determine an individual’s exact biological age.
Chapter 1: You Are as Young as You Feel
So, in essence, the epigenetic clock allows for calculation of the difference between chronological and biological age – the pace of ageing. There has been recent hype surrounding this and there are now products on the market that claim to accurately determine biological age. At the time of writing, in my view, they should be approached with caution. Our research shows that, as yet, the methods are not sufficiently sensitive or specific to give accurate estimates of an individual’s biological age and do not take into consideration all of the complex network of factors that influence the ageing process. But this is a fast-evolving area of research and no doubt more accurate tests of biological age are quickly coming down the track. In recent years, we have learned much more about the many factors that affect epigenetic clocks. Those that adversely affect our clocks are illness, bad health behaviours (smoking or obesity) and stressful life experiences. Age acceleration occurs when our clocks speed up as a consequence of these events or behaviours. Another area that influences biological ageing is mood. The Canadian singer-songwriter Justin Bieber sleeps in a hyperbaric oxygen chamber, allegedly to relieve anxiety. Perhaps this is not as outlandish as it first appears. Persistent stress and mood change, such as depression and anxiety, can cause long-term damage from over-exposure to stress hormones and the adverse physiological state they create. A well-known New Zealand study, the Dunedin Study, followed 1,000 participants, all born between April 1972 and March 1973, with detailed testing at regular intervals since birth. At ages 26, 32 and 38, detailed health checks were carried out and blood tests were measured for biological ageing. This was coupled with details of the participants’ perceptions of how they were ageing – their ageing attitudes. David Belsky and Terrie Moffitt, the lead investigators for the study, reported that some of the 38-year-olds had the epigenetic biological age of a 28-year-old, whereas others had the biological age of a 48-year-old (see opposite). Participants with a chronological age of 38 years in the Dunedin Study showing the spread of biological ages from 28 to almost 50 years.
Chapter 1: You Are as Young as You Feel
What was the reason for this almost 22-year variation in biological ageing, even as early as 38? The big driver was low mood and stress, particularly in childhood but also in participants’ twenties and thirties.
Furthermore, Belsky and Moffitt tested the hypothesis that those who were biologically older than their chronological age of 38 were continuing to age faster than peers of the same chronological age who retained ‘younger’ physiologies. They found that a 38-year-old with a biological age of 40 aged 1.2 years faster over the course of 12 years compared with a peer whose chronological age and biological age was 38. In other words, individuals who were biologically older at the first time of data collection continued to age at a faster pace during subsequent years. Furthermore, the pace of physiological deterioration was evident across multiple organ systems: the lungs, mouth, gums and teeth, heart rate and blood pressure, kidneys, liver, eyes, immune function, bone, blood lipids, diabetes markers, body mass index, body fat and the brain. In faster agers, all organs were ageing faster; accelerated ageing was not just confined to one system, it was universal. This suggests that a common mechanism explains biological ageing. If we can pin down this mechanism we could have the key to the elixir of youth.
Chapter 1: You Are as Young as You Feel
Already, before midlife, the young adults who were ageing more rapidly were also less physically able. For example, they had poorer balance, unable to stand on one leg for as long as slow agers; had clumsier fine-motor skills, when tested by placing small objects into holes on a pegboard, and had weaker grip strength.
Although young adults were disease free at the time of testing, the test results exposed problems in systems that would ultimately lead to age-related disease – for example, the eyes. The eye is the window to the brain. Small blood vessels in the eye originate from the same source as the small vessels that go to the brain. This shared starting point enables us to draw conclusions about brain vessels from eye vessels in adults. Changes detected in retinal photographs predict future stroke and vascular dementia. Young adults in the Dunedin Study who had older biological age had significantly ‘older’ eye vessels, thus raising the possibility that they were at a higher risk of stroke and dementia later on in life.
In a parallel experiment, undergraduate students who did not know the study participants or their details were asked to rate facial photographs of them. The students were able to accurately identify differences in the facial ageing of the study members which mirrored biological ageing – they picked out the faster agers as looking ‘older’. The faster agers also said they felt older and perceived themselves to be in a poorer state of health.