Remaining illness-free as the human lifespan continues to increase

People are living much longer today than in previous generations. This is good but carries the downside that, for most people, the longer you live the more illnesses characteristic of older age pile up, eg cancer, dementia, etc.

The new discipline of geroscience tackles the root causes of ageing, aiming to postpone the onset of diseases and disabilities that can make old age miserable and squeezing the illnesses that accompany old age into a much shorter time-frame. This approach was described by Cassandra Willyard last January in Science News, who asked, “is ageing without illness possible?”, and by Richard Faragher in The Conversation in January 2021.

One of the most significant developments in history was the doubling of the average human lifespan from about 30 years in the 1800s to more than 70 years today, under the influence of scientific medical and public health developments. The ageing of the world’s population is dramatic.

Willyard quotes UN statistics that one billion people will be at least 65 years old by 2030 and, by 2100, five billion people will be 65 and over. Because this increased life expectancy is accompanied by the development of many age-related diseases such as cancer, type two diabetes and so on, the demographics projected by the UN pose an enormous challenge to our healthcare and nursing home systems.

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As we age beyond middle age our basic biological organisation deteriorates. Our immune system weakens, making us increasingly susceptible to disease, some cells stop dividing, DNA degrades and cancer, heart disease, type two diabetes, brittle bones, dementia, and so on, can develop. Many people spend their final decade(s) burdened by one or more such maladies. And so, there is an urgent need to develop new drugs that will keep older people healthy, independent and active for longer.

Until relatively recently, medical scientists believed deterioration in health and performance in old age was inevitable. However, research in the 1980s and 1990s gave cause for hope that ageing might be manipulated when it was discovered that certain gene mutations in the roundworm C Elegans doubled its lifespan. Interesting also was the realisation that a number of drugs, originally developed to treat conditions unrelated directly to ageing, could be repurposed as anti-ageing drugs. The two best known examples are rapamycin and metformin.

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Rapamycin is widely prescribed for people who receive transplants to help their immune systems to accept the foreign tissue. The drug reduces inflammation, clears out old and damaged cells and alters metabolism, acting on some of the key factors researchers think are to blame for the ageing process. Rapamycin has been shown to extend the lifespan of mice by 15 per cent and dramatically improves immune function and vaccine response in older humans.

Metformin was originally licensed to treat type two diabetes but after decades of experience, researchers noticed that patients using the drug had lower rates of death and illness than those not using the drug. It works by suppressing the inflammation caused by senescent cells. Other drugs are also being tested and reports of improved immune function and performance in elderly adults are coming in. Old drugs such as rapamycin and metformin have a tremendous advantage over newly-discovered drugs in that millions of dollars have already been spent to show they are not dangerous to their hosts.

Some cells in older people stop dividing but remain alive – senescent cells. These cells disrupt the orderly metabolism of the tissues they live in, induce more senescence in neighbouring cells, release chemicals that cause inflammation and interfere with tissue repair. A class of drugs called senolytics eliminate senescent cells by inducing programmed cell death. One such drug is fisetin, a flavonoid found in many fruits and vegetables (strawberries are rich in fisetin). Promising results have been reported in mice and these are being followed up in human trials.

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Many anti-ageing drug trials are first conducted in species such as yeast, worms and mice, animals that have short lifespans, allowing researchers to extract trial results relatively quickly. Getting results from human trials takes a lot more time. But, of course, human trials are essential and so geroscience must advance slowly.

It is very probable that a geroscience revolution is coming – but what do we do in the meantime? Well, we are not bereft of good advice presently on how to improve healthspan – eat a balanced diet, get plenty of aerobic and resistance exercise, take your vaccinations, avoid tobacco and drink alcohol sparingly.

William Reville is an emeritus professor of biochemistry at UCC