Every few weeks or months, the media reports on a new study that tantalisingly dangles the possibility of a new drug to give us longer, healthier lives.

The latest study centres around a drug involved in targeting interleukin-11, a protein involved in inflammation. Blocking this protein appeared to help mice stave off disease and extend their life by more than 20%.

If only defying the ravages of time could be achieved through such a simple and effort-free way – by taking a pill. But as is so often the case, the real-world significance of these findings falls a fair way short of the hype.

The role of inflammation in disease and ageing

Chronic inflammation in the body plays a role in causing disease and accelerating ageing. In fact, a relatively new label has been coined to represent this: “inflammaging”.

While acute inflammation is an important response to infection or injury, if inflammation persists in the body, it can be very damaging.

A number of lifestyle, environmental and societal drivers contribute to chronic inflammation in the modern world. These are largely the factors we already know are associated with disease and ageing, including poor diet, lack of exercise, obesity, stress, lack of sleep, lack of social connection and pollution.

While addressing these issues directly is one of the keys to addressing chronic inflammation, disease and ageing, there are a number of research groups also exploring how to treat chronic inflammation with pharmaceuticals. Their goal is to target and modify the molecular and chemical pathways involved in the inflammatory process itself.

What the latest research shows

This new interleukin-11 research was conducted in mice and involved a number of separate components.

In one component of this research, interleukin-11 was genetically knocked out in mice. This means the gene for this chemical mediator was removed from these mice, resulting in the mice no longer being able to produce this mediator at all.

In this part of the study, the mice’s lives were extended by over 20%, on average.

Another component of this research involved treating older mice with a drug that blocks interleukin-11.

Injecting this drug into 75-week old mice (equivalent to 55-year-old humans) was found to extend the life of mice by 22-25%.

These treated mice were less likely to get cancer and had lower cholesterol levels, lower body weight and improved muscle strength and metabolism.

From these combined results, the authors concluded, quite reasonably, that blocking interleukin-11 may potentially be a key to mitigating age-related health effects and improving lifespan in both mice and humans.

Why you shouldn’t be getting excited just yet

There are several reasons to be cautious of these findings.

First and most importantly, this was a study in mice. It may be stating the obvious, but mice are very different to humans. As such, this finding in a mouse model is a long way down the evidence hierarchy in terms of its weight.

Research shows only about 5% of promising findings in animals carry over to humans. Put another way, approximately 95% of promising findings in animals may not be translated to specific therapies for humans.

Second, this is only one study. Ideally, we would be looking to have these findings confirmed by other researchers before even considering moving on to the next stage in the knowledge discovery process and examining whether these findings may be true for humans.

We generally require a larger body of evidence before we get too excited about any new research findings and even consider the possibility of human trials.

Third, even if everything remains positive and follow-up studies support the findings of this current study, it can take decades for a new finding like this to be translated to successful therapies in humans.

Until then, we can focus on doing the things we already know make a huge difference to health and longevity: eating well, exercising, maintaining a healthy weight, reducing stress and nurturing social relationships.

Hassan Vally, Associate Professor, Epidemiology, Deakin University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

A recent study has suggested Shingrix, a relatively new vaccine given to protect older adults against shingles, may delay the onset of dementia.

This might seem like a bizarre link, but actually, research has previously shown an older version of the shingles vaccine, Zostavax, reduced the risk of dementia.

In this new study, published last week in the journal Nature Medicine, researchers from the United Kingdom found Shingrix delayed dementia onset by 17% compared with Zostavax.

So how did the researchers work this out, and how could a shingles vaccine affect dementia risk?

From Zostavax to Shingrix

Shingles is a viral infection caused by the varicella-zoster virus. It causes painful rashes, and affects older people in particular.

Previously, Zostavax was used to vaccinate against shingles. It was administered as a single shot and provided good protection for about five years.

Shingrix has been developed based on a newer vaccine technology, and is thought to offer stronger and longer-lasting protection. Given in two doses, it’s now the preferred option for shingles vaccination in Australia and elsewhere.

In November 2023, Shingrix replaced Zostavax on the National Immunisation Program, making it available for free to those at highest risk of complications from shingles. This includes all adults aged 65 and over, First Nations people aged 50 and older, and younger adults with certain medical conditions that affect their immune systems.

What the study found

Shingrix was approved by the US Food and Drugs Administration in October 2017. The researchers in the new study used the transition from Zostavax to Shingrix in the United States as an opportunity for research.

They selected 103,837 people who received Zostavax (between October 2014 and September 2017) and compared them with 103,837 people who received Shingrix (between November 2017 and October 2020).

By analysing data from electronic health records, they found people who received Shingrix had a 17% increase in “diagnosis-free time” during the follow-up period (up to six years after vaccination) compared with those who received Zostavax. This was equivalent to an average of 164 extra days without a dementia diagnosis.

The researchers also compared the shingles vaccines to other vaccines: influenza, and a combined vaccine for tetanus, diphtheria and pertussis. Shingrix and Zostavax performed around 14–27% better in lowering the risk of a dementia diagnosis, with Shingrix associated with a greater improvement.

The benefits of Shingrix in terms of dementia risk were significant for both sexes, but more pronounced for women. This is not entirely surprising, because we know women have a higher risk of developing dementia due to interplay of biological factors. These include being more sensitive to certain genetic mutations associated with dementia and hormonal differences.

Why the link?

The idea that vaccination against viral infection can lower the risk of dementia has been around for more than two decades. Associations have been observed between vaccines, such as those for diphtheria, tetanus, polio and influenza, and subsequent dementia risk.

Research has shown Zostavax vaccination can reduce the risk of developing dementia by 20% compared with people who are unvaccinated.

But it may not be that the vaccines themselves protect against dementia. Rather, it may be the resulting lack of viral infection creating this effect. Research indicates bacterial infections in the gut, as well as viral infections, are associated with a higher risk of dementia.

Notably, untreated infections with herpes simplex (herpes) virus – closely related to the varicella-zoster virus that causes shingles – can significantly increase the risk of developing dementia. Research has also shown shingles increases the risk of a later dementia diagnosis.

The mechanism is not entirely clear. But there are two potential pathways which may help us understand why infections could increase the risk of dementia.

First, certain molecules are produced when a baby is developing in the womb to help with the body’s development. These molecules have the potential to cause inflammation and accelerate ageing, so the production of these molecules is silenced around birth. However, viral infections such as shingles can reactivate the production of these molecules in adult life which could hypothetically lead to dementia.

Second, in Alzheimer’s disease, a specific protein called Amyloid-β go rogue and kill brain cells. Certain proteins produced by viruses such as COVID and bad gut bacteria have the potential to support Amyloid-β in its toxic form. In laboratory conditions, these proteins have been shown to accelerate the onset of dementia.

What does this all mean?

With an ageing population, the burden of dementia is only likely to become greater in the years to come. There’s a lot more we have to learn about the causes of the disease and what we can potentially do to prevent and treat it.

This new study has some limitations. For example, time without a diagnosis doesn’t necessarily mean time without disease. Some people may have underlying disease with delayed diagnosis.

This research indicates Shingrix could have a silent benefit, but it’s too early to suggest we can use antiviral vaccines to prevent dementia.

Overall, we need more research exploring in greater detail how infections are linked with dementia. This will help us understand the root causes of dementia and design potential therapies.

Ibrahim Javed, Enterprise and NHMRC Emerging Leadership Fellow, UniSA Clinical & Health Sciences, University of South Australia

This article is republished from The Conversation under a Creative Commons license. Read the original article.