Tackling ageing could be a better way of treating and preventing multi…

Over half of UK adults over the age of 65 live with two or more long-term health conditions – commonly known as multimorbidity. People living with multimorbidity not only have a shorter life expectancy, but they may also experience poorer physical and mental health.

Crucially, over half of GP consultations and hospital appointments include patients with multimorbidity. In the UK, care for people with multimorbidity is also estimated to take up to 70% of health and social care expenditure. With an ageing population, it’s expected that the number of people living with multimorbidity will rise. This could place an already greater need on the NHS by patients needing long term treatment.

Multimorbidity is currently managed by treating each disease separately. This method people will need to take multiple medications at the same time (known as polypharmacy), and will also have to attend multiple medical appointments for each condition. Not only can this put a strain on the NHS, polypharmacy can also put patients at increased risk of negative drug interactions and unintended harm.

There’s a clear need to enhance the way multimorbidity is treated. But research shows that in order to do this, we need to instead start looking at targeting the meaningful causes of multimorbidity when searching for treatments.

A new approach

Although multimorbidity differs for each person, we know that patients tend to suffer from the same groups of diseases – known as “clusters”. This indicates that each cluster may proportion a shared inner cause. For example, a person with multimorbidity may suffer from heart problems (such as heart disease and high blood pressure) and diabetes, which may all grow out of the same cause – such as obesity.

Identifying and treating the cause of a patient’s disease clusters would allow us to more effectively combat several – or already all – of the diseases a patient has using a single treatment. This would both reduce the number of medical appointments a person needs to attend and the number of medications they may need to take.

People with multimorbidity often need to take multiple medications to manage their conditions.
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Such an approach has not however been taken, in large part because medical research and drug discovery tends to focus on treating a single disease, instead of multiple. So any breakthroughs in this field could be many years off unless action is taken now.

Importantly one of the biggest risk factors for developing multimorbidity is getting older. This is why researchers think targeting the biological causes of ageing could be one way of treating multimorbidity, by preventing clusters of diseases from developing in the first place.

Ageing is characterised by nine changes – known as the “hallmarks of ageing” – that occur in our cells and molecules. These changes consequence from a build-up of damage in the body, which then stresses our cells and causes them to go into a state known as cell senescence, where the cell stops dividing and then causes further damage to healthy cells.

We become less able to remove senescent cells from our body as we get older, causing them to build up and increase our risk of disease. Researchers think that if we could prevent these cells from building up, we may be better able to prevent multimorbidity from happening to begin with.

Research on mice that were genetically engineered to have no senescent cells showed they lived 25% longer and had less multimorbidity than normal mice. But mice that had been genetically engineered to have increased cell senescence aged faster and developed multimorbidity younger. Though the same will need to be proven in humans, these early results show targeting senescent cells may have potential in preventing multimorbidity.

Drugs which can kill senescent cells (called senolytics) already exist, and are currently used to treat certain types of leukaemia, and are now being trialled on patients with the chronic lung condition idiopathic pulmonary fibrosis. Given senolytics are already in clinical use, this method they could quickly be repurposed for use in patients with multimorbidity if proven to be effective on other conditions too.

Physical activity may also be another way to target senescent cells. Studies on mice have shown that exercise can help reduce the number of senescent cells in the body. Some evidence also indicates the same is true for humans. One study, which had older adults follow a daily exercise programme for 12 weeks, found that not only did participants’ physical function enhance, the number of senescent cells they had in their blood was reduced.

But before we can use this kind of approach in treating multimorbidity, more research will be needed. Not only do we need to show that drugs which target biological ageing work at preventing and treating multimorbidity in humans, we also need to clarify which hallmarks of ageing are driving clusters of disease to develop in patients with multimorbidity.

With an ageing population in many countries around the world, multimorbidity is likely to only become more shared unless a drastic new approach is taken to tackle it. Better treatments alone could have a major impact on improving the physical and mental health of patients worldwide – while also alleviating pressure on healthcare systems.

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