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Telomerase activation just might lead to cures for ageing itself

My Times column on the possibility that old age might itself be cured now we understand telomeres:


Squeezed between falling birth rates and better healthcare, the world population is getting rapidly older. Learning how to deal with that is one of the great challenges of this century. The World Health Organisation has just produced a report on the implications of an ageing population, which — inadvertently — reveals a dismal fatalism we share about the illnesses of old age: that they will always be inevitable.

This could soon be wrong. A new book, The Telomerase Revolution, published in America this week by the doctor and medical researcher Michael Fossel, argues that we now understand enough about the fundamental cause of ageing to be confident that we will eventually be able to reverse it. This would mean curing diseases such as Alzheimer’s, heart disease and osteoporosis, rather than coping with them or treating their symptoms.

Let me show you what I mean about fatalism. The WHO report on ageing and health, for all its talk of the need for “profound changes” to health care for the elderly, actually urges us to stop trying to cure the afflictions of old age and learn to live with them: “The societal response to population ageing will require a transformation of health systems that moves away from disease-based curative models and towards the provision of older-person-centred and integrated care.”

Yet it also subscribes to the somewhat magical hope that illnesses of old age can be “prevented or delayed by engaging in healthy behaviours” and that “physical activity and good nutrition can have powerful benefits for health and wellbeing.” This is largely wishful thinking. There is no evidence that, say, Alzheimer’s can be prevented by a certain diet or activity. A lack of activity and poor nutrition can worsen health at any age, but the underlying chronic diseases of old age are caused by age itself.

When I asked Dr Fossel what he thought of the WHO report, he replied: “In 1950 we could have talked (and did) about ‘active polio’ in the sense of keeping polio victims active rather than giving up, but the very phrase itself implies that one has already given up. I would prefer that we cure the fundamental problem. Why talk about ‘active ageing’, ‘successful ageing’, and ‘healthy ageing’ when we could talk about not ageing?”

Dr Fossel is one of the pioneers of research into the clinical use of telomerase, an enzyme that causes certain kinds of cell to be effectively immortal. These include free-living protozoa, cancer cells and the germ cells that give rise to sperm and eggs. When you think about it, the fertilised egg from which you grew had three billion years of continuous life under its belt when it turned into you, and didn’t look a day over zero.

That’s because of telomerase. It resets the activity level of genes so that each life starts young. Telomerase does this by re-lengthening highly repetitious bursts of DNA sequences called “telomeres” on the tips of chromosomes. The six-letter string TTAGGG is repeated 15,000 times on each chromosome tip in most of your cells when you are a baby but only 8,000 times when you are old. That shortening is the primary cause of ageing.

Apart from your germ cells and some stem cells, all the other cells in your body shut down their telomerase genes, with the result that their telomeres get shorter with each cell division. Age is not the accumulation of wear and tear; it’s the shortening of telomeres, leading — we are still not entirely sure how — to a slowdown in the rate at which damaged molecules are repaired which in turn leads to a greater number of damaged cells.

An analogy may help. My mobile phone currently has a cracked front; I’m living with that till I am next due an upgrade. If upgrades come round quickly, most mobile phones are in good order. If they come round more slowly, more people have damaged mobile phones. As you age, your cells upgrade their molecules more slowly, because their telomeres are shorter. So there are more damaged cells.

What startles me about Dr Fossel’s book is his evidence that this phenomenon explains all the chronic diseases of ageing, even ones such as dementia. Until recently, it was thought that these diseases could not be linked to telomere shortening because they involve cells that do not divide: neurons, for instance. But we now know that other cells called microglia, which do divide, are crucial to the functioning of neurons. A similar argument applies to heart cells and the cells that line arteries.

In 1999 scientists working for Geron, a biotech firm, demonstrated that adding telomerase could reset the clock of ageing and rejuvenate a cell. They went on to show that they could take skin cells from an old person, treat them with telomerase, and grow skin typical of a young person. All it takes now, says Dr Fossel, is to work out how to boost telomerase in our cells in a safe way. Not a trivial problem, but probably not an insuperable one, in the rapidly advancing state of gene therapy.

Dr Fossel has founded a company, Telocyte, to try this approach for people with Alzheimer’s. He may not succeed, but if somebody does, the implications are profound. Suppose people could take a course of pills or injections to reverse dementia, Parkinson’s, heart disease or osteoporosis. Suppose that people in their nineties could live genuinely “healthy” lives, as if they were fifty, not the managed decline that the WHO report recommends.

In such a world, the costs of treating chronic diseases of old age, and of social care for the elderly could fall. The problem of an ever-smaller working population supporting an ever-growing population of the infirm elderly could disappear, as 90-year-olds went back into full-time jobs. On the other hand, the decline in world population growth — with a stable level expected by 2080 or so — might eventually reverse, creating another population boom.

Fanciful? Maybe, but given what we now know about telomeres, and the mechanism that lies behind ageing, it is not as mad as assuming the world will continue as it is. The WHO’s vision of a world in 2050 in which governments are devoting much more money and effort to making people comfortable in nursing homes as they live with chronic dementia, disability and decline may well be even more implausible. The future is not just a straight-line extrapolation of the past.

By Matt Ridley | Tagged:  rational-optimist  the-times