Except in the case of terminal or degenerative disease, and outside the cells of the condemned, nobody knows how much time they have remaining on this mortal coil. “For man also knoweth not his time,” says Ecclesiastes 9:12 (King James version), but recent developments in biomedical science are set to put pay to this millennial maxim.
A research paper published in last week’s Genome Biology entitled “DNA methylation age of blood predicts all-cause mortality in later life” looked at subtle changes in subjects’ DNA, related these to biological ageing, and investigated whether the difference between a subject’s measured biological age and actual age (Δage) could be used to predict mortality. In the words of the authors “a five-year higher Δage is associated with a twenty-one per cent higher mortality risk, adjusting for age and sex”. After taking into account childhood IQ, education, social class, hypertension, diabetes and cardiovascular disease this association was still strong at sixteen per cent.
The science behind the Genome Biology article is quite complex. One of the many ways the expression of genes is controlled is through DNA methylation. Individual genes or even large swathes of chromosomes can be turned off by the methylation process, the ultimate effect of which is the conversion of DNA into something called heterochromatin, akin to a hibernating form of the molecule. Methylation is associated with the developmental process. Different cells in different parts of the body are methylated in different ways — a liver cell will have different methylation patterns to a neuron. The phenomenon can also account for the differences between individuals: some work I did a number of years ago showed that carnation plants with ovate leaves had different methylation patterns than those with lanceolate leaves. Methylation is also associated with aging: the older you get the more your genes are modified in this way.
So now, in light of the Genome Biology paper, scientists will be able to take a patient’s blood, extract the DNA, and with the help of Illumina Human Methylation 450 Bead Chips measure methylation levels. By way of a standard curve the patient’s biological age will be calculated and this figure will be compared to actual age. If the patient’s Δage is more than five, he or she is given the news that their risk of mortality is increased.
I can see the business plans being written as I type. Very soon you and I will be able to send our blood off to be tested for methylation levels — for a fee of course. Predictive medicine is already huge business and we are merely standing on the threshold of a brave new world where not only will predisposition to various forms of cancer, diabetes, high cholesterol, autism, Alzheimer’s et cetera be tested for, but we will be able to find out when and how our sojourn among the living will come to an end. There is already a company that will measure the length of your chromosomes’ telomeres (another indication of biological age: short telomeres = start getting measured up for that coffin!).
Around the time the genetic test for Huntington’s disease (HD) was developed, I remember a genetics lecturer of mine identifying one problem with these predictive genetic tests: what do you do with the knowledge? In the case of HD there is no cure and the terrible neurological decline seen in the disease’s progression is unstoppable. Finding out you have HD is akin to being granted the gift to see the Sword of Damocles hovering over you, but being powerless to do anything about it. There are great moral debates concerning the ethics and even utility of learning at twenty that one will succumb in late middle age to a harrowing, incurable neurodegenerative disease.
Similarly, what is the use of knowing that your Δage is greater than five or your telomeres are shorter than they should be? You’re essentially being told that your true, biological age is greater than your “on-paper” age, and that you’ve less time and health than you’d counted on. While the likes of Cher and Jane Fonda through plastic surgery, diet and exercise have managed to stem many of the external signs of aging, science has not yet come up with a formula to demethylate the areas of the genome involved in aging, or lengthen those shortening telomeres. There is no little pill able to squirm inside your cells and turn back the biological molecular clock.
I can identify a couple more ethical qualms with these emerging genetic tests for health and lifespan. Firstly, the diagnoses they give are vague and non-specific. In light of an analysis showing up a high Δage, what does a physician say to a patient?: “I’d lay off the beer, Mr Smith, and I’m writing you a prescription for rhubarb juice and fennel tea. Six gallons a day of each.” And what is the patient to think? That although he’s feeling hunky-dory at present, the short span of life he may be left with will be a rapid downward spiral plagued by ill health, and there is very little he can do about it? Presumably, though, the younger you submit to a methylation or telomere-length analysis, the greater your heads-up, and the higher the success rates of whatever interventions medics might recommend. At thirty if you’re told your methylation levels are running high you may be able to halt or slow the genomic aging process through changes in lifestyle: a diet high in antioxidants and low in fats and red meats; no smoking; no alcohol; long hours of sleep; plenty of light exercise. If, on the other hand, you find out at sixty that your Δage is greater than five, it is very unlikely that daily drinking of gallons of avocado smoothie are going to do you any good.
Secondly, this is rich man’s medicine. In a world where millions go without life-saving basics such as vaccines, antibiotics, anti-inflammatories and even clean drinking water, should resources be pumped into the development of dubious assays for the aging and wealthy? The appearance of these tests is just highlighting what will be an irreversible trend in this century — out-of-this-world medical treatment for the rich (personalised, predictive, preventative medicine; prosthesis; robotics; upgrades; plastic surgery; anti-aging and -obesity treatments; cures for baldness, acne, allergies and bad posture) while kids die needlessly of dysentery, malaria and malnutrition in the Third World.