Scientists are increasingly approaching ageing as a disease that can be understood and treated so that we can live far longer, and healthier, lives in the future.
"I think definitely the prospect of living to 120 in good health – that is more and more likely," says Luke O'Neill, professor of biochemistry at Trinity College Dublin.
We are living longer, certainly, with the average Irish man now living to 78.3 years and average Irish woman reaching 82.7 years, according to the Central Statistics Office (CSO). That is an increase of 20.9 years for men and 24.8 years for women since the first official table on Irish life expectancy was produced in 1926.
Many scientists believe human longevity will hit a wall somewhere around 120 years, while a smaller number believe lifespan can increase indefinitely.
What is probably more important is the number of healthy years we can live.
The figures here are less impressive.
According to an EU healthy-life measure, health in Ireland begins to deteriorate on average at 66 for men and 67 among women.
For scientists therefore, the name of the game is first and foremost to try and increase the number of years that people can live healthy, active lives. And there are a number of scientific strategies and approaches to try and tackle the “problem of ageing”, with Irish researchers leading the charge.
Danny Kelly is a professor at the school of engineering in Trinity. He was awarded a prestigious grant from the European Research Council in September to develop new treatments for osteoarthritis.
Osteoarthritis is a disease of the joints caused by the breakdown of cartilage and bone tissue inside the joint, and leads to pain and loss of joint function . It affects an estimated 45,000 people in Ireland.
The treatment at the moment is to replace diseased hips or knees with metal and plastic (polymer) implants. Kelly is aiming to develop a way of using 3D “bioprinting” technology to print a biological implant that will regenerate and replace damaged tissues in a diseased joint.
The metal-plastic implants used in diseased joints today last for between 10 and 15 years, and result in reduced pain and increased joint function for the patient. For people under 70 with diseased joints, the likelihood is that they will need to replace their implants.
We can deposit cells at different points inside a printed part
Kelly believes that biological implants for diseased joints will provide a solution that can last for a lifetime even in relatively young patients.
The 3D printing technology used to render the biological implants works in a similar way to a standard colour printer, he says. In this case, however, instead of ink, living cells are mixed with a liquid and fed into the printer.
“It’s the same technology that is used to put different colours on a piece of paper when we are doing traditional inkjet printing,” says Kelly. “We can deposit cells at different points inside a printed part. The challenge is making sure that the cells stay alive and viable and can perform their normal function after we print them.”
The Trinity team is developing implants using materials that are “biocompatible” with the body, have mechanical strength and are biodegradable. This work is taking place in the context of efforts by researchers worldwide to use 3D bioprinting technology to produce “off the shelf” organs for those who need them.
Over the next five-10 years, Kelly estimates, it will be possible to bioprint simpler organs for those who need them, including the older population. This could negate the need for people to wait on a list for an organ donation.
Tom Cotter is professor of biochemistry at University College Cork where he researches age-related degenerative eye conditions. According to Fighting Blindness, who part-fund Cotter's research, there are 100,000 people living with age-related macular degeneration (AMD) in Ireland, which can result in blurred or lost vision in the centre of the eye's visual field.
Cotter has found that progesterone is a “very good neuroprotectant” and delays the loss of eyesight in animal models of human eye disease, such as AMD.
The hormone acts as an antioxidant in the ageing eye, says Cotter, and given that antioxidants cause damage to people’s eyes as they age, this is beneficial. The fact that a hormone found in greater concentrations in women protects an organ against ageing makes sense, he says, given that women live longer than men on average.
Cotter believes that not only do “female hormones” protect against ageing, but that the “male hormone”, testosterone, helps ensure men will die younger.
Eunuchs who were high up in the royal hierarchy – and these are men that would have been castrated – lived on average 15-20 years longer
The evidence he cites to support this comes from an unusual source; the records of the Korean imperial court from the 17th to the 19th century.
“The Koreans were very good at keeping genealogical records,” says Cotter. “What they found was that eunuchs who were high up in the royal hierarchy – and these are men that would have been castrated – lived on average 15-20 years longer than uncastrated men.”
There is further evidence to support this in medical records from the early part of the 20th century, says Cotter, when therapeutic castration was used for men with mental health disorders. “Men who were castrated in these mental health institutions; they actually lived longer than their uncastrated counterparts.”
One strategy to combat ageing, says Cotter, is to develop methods to grow new organs and have people go into hospital when they hit 60, 70 or 80 and have their heart, lungs or kidneys replaced as they wear out. This is certainly a possibility in the future.
However, Cotter says that while it may be possible to replace the major organs in the body in this way, it will be more difficult to replace the minor ones. A better strategy, he says, would be to prevent the body as a whole from ageing, and, to do this, scientists need to prevent ageing in individual cells.
Some promising work in this regard has been done in fruit flies, says Cotter, with scientists preventing telomeres – tail-like structures situated at the end of the chromosomes that hold our DNA – from shortening.
This research is exciting because the shortening of telomeres has been been associated with an internal clock that drives ageing since the idea was first put forward by American anatomist Leonard Hayflick in 1961. The Hayflick limit means that a normal human cell divides a certain number of times, as its telomeres shorten, and then stops.
When a cell stops dividing it no longer carries out its associated functions. In turn, the chromosomes become unstable as more cells deteriorate, thus driving the ageing process.
An enzyme called telomerase, found in young cells, prevents the kind of wear and tear on the telomeres that causes them to shorten. In older cells telomerase becomes less active.
“In these fruit flies, scientists have stabilised this enzyme [telomerase] so the enzyme does not lose its activity and you can increase the lifetime of the fly two or three fold,” says Cotter. “Now, we might say can we extend that to humans and that’s, of course, the $64,000 question. But, if you are looking into the future it is probably better to do something like that, to prevent all the cells in the body from ageing, rather than trying to replace old organs because I think that’s going to be too difficult and too invasive.”
Another way to increase lifespan is to reduce calorie intake in the diet, says Cotter. It has been shown in rats, mice and monkeys that a 30 per cent reduction in calorie intake will increase the lifespan.
“There is one monkey who was put on a restricted diet, his calories were cut by 30 per cent, when he was 16 years of age,” says Cotter. “He is now 43 years of age, that’s quite old for a money, and if you turn monkey years into human years he would be about 130 years old.”
Meanwhile, Prof Luke O’Neill, an immunologist, believes ageing has a lot to do with the body’s immune system and how it reacts, through a process called inflammation, to protect the body.
“There is a term called ‘inflam-ageing’, which is kind of a funky term that relates the inflammatory process to ageing,” says O’Neill. “It’s almost as if noxious things are building up as we get older and our body can’t handle them. A good example is the skin. The skin eventually loses its elasticity because it’s not able to handle the damage that is inflicted on it as we get older.”
There’s a protein in the immune system called NLRP3, says O’Neill, which drives inflammation and research at his lab has found various ways to impede NLRP3 and slow down the inflammation that damages tissues as we age.
O’Neill set up a company called Inflazome through which a drug is being developed to block NLRP3.
We could be living into a very nice, healthy old age, doing stuff that is really fulfilling
This means that progression of common, age-related inflammatory diseases such as glaucoma, arthritis and Alzheimer’s disease can be slowed in future.
This will have a huge impact on individual lives, as well as wider societal economic benefits by reducing costs of healthcare and keeping people in work for longer.
What will this longer life, healthier future look like or all of us then?
“You mightn’t be doing tedious jobs,” says O’Neill. “The future is robotics remember, so we could be living into a very nice, healthy old age, doing stuff that is really fulfilling.”
‘ALZHEIMER’S CURE WILL COME, BUT NOT IN TIME FOR ME’
Ronan Smith from Dublin, who now lives in Wicklow, was diagnosed with the inherited form of Alzheimer's disease in 2014.
The 59-year-old describes having Alzheimer’s as his second dementia journey, because he cared for his father in the 1980s when he developed the disease. At that time, Ronan said, there was a lot of stigma and ignorance around Alzheimer’s and his father hid his condition before the family finally had to place him into care.
When he was 51, Ronan – who was working in the theatre production business – began to observe symptoms developing in himself that he recognised from treating his father. He hoped it might be depression or anxiety rather than Alzheimer’s and so continued on, until he went for a test in 2013 and was diagnosed in 2014.
The positive diagnosis had serious implications for his two young adult children too, as there is a 50-50 chance for each child of a parent with inherited Alzheimer’s that they too will develop the condition.
“I have shared all the information I have with them,” says Smith. “They are understandably saying, well I’m going to get on with my life. I think only if they were in a serious relationship and thinking of children, then maybe you’d think about it [getting tested] but you might not.”
Smith closely follows new Alzheimer’s research, and took part in a clinical trial over an 18-month period for a drug called Nilvad. “When the drug was run through it didn’t signal any real, definable benefit,” says Smith.
He believes there will be a cure for Alzheimer’s, whether it be in Ireland or elsewhere, as there are so many researchers worldwide trying to make the breakthrough.
“Without being too bleak about it, I would say though that the chances are that whatever is the breakthrough it is possibly not going to recover mental faculties that have been damaged,” says Smith.
OLD ORDER AMISH
The recent discovery of a rare genetic mutation that prolongs human life has raised hopes for new treatments to combat ageing and prevent age-related disorders from heart disease to dementia.
Researchers spotted the mutation in an Amish population in Indiana where carriers were found to have better metabolic health, far less diabetes, and tended to live a decade longer than others in the community.
Those with the mutated version of the gene typically lived to 85 years old, a full 10 years longer
Scientists studied 177 members of the Old Order Amish in the US town of Berne and identified 43 people who had inherited one normal and one mutated version of a gene called Serpine1. Those with the mutated version of the gene typically lived to 85 years old, a full 10 years longer than those who did not carry the mutated form.
“This is a rare genetic mutation that appears to protect against biological ageing in humans,” says Douglas Vaughan, a professor of medicine who led the research at Northwestern University in Chicago.
The Serpine1 gene provides the body with instructions to make a protein called PAI-1 which serves as a brake on a process that destroys any clots that may build up in blood vessels. But the protein also has a hand in a process called senescence, where cells go into a state of suspended animation and steadily build up in the body’s tissues. Senescence is increasingly thought to be a strong driver of the ageing process.
Writing in the journal Science Advances, the researchers describe how those with the single mutated gene had 50 per cent lower levels of PAI-1 in their blood. Carriers of the mutation also had longer telomeres than others, suggesting they had aged more slowly, the scientists report.