The term ‘inflammageing’ was first coined by Dr Claudio Franceschi in the early 2000s and has recently emerged as a major new health issue.

It describes the chronic, low-grade inflammation that naturally increases with age; it constitutes a major risk factor for the onset and progression of various age-related diseases, such as Alzheimer's, cardiovascular disease, diabetes, cancer and frailty.

This concept highlights the link between inflammation and the ageing process, suggesting a heightened level of basal inflammation in the elderly. 

Further research is needed to understand and mitigate the detrimental effects of chronic low-grade inflammation on age-related diseases.

What causes ‘inflammageing’?

‘Inflammageing’ involves a complex interplay of biological processes altered by age, including the immune function, genetic factors, metabolic health and the gut microbiome.

· Ageing: With age, the body undergoes numerous biological changes that can disrupt normal cellular functions. One of the main features of ageing is that it is associated with a gradual decline in the immune system, making it less effective at regulating inflammation, resulting in increased susceptibility to inflammatory diseases and a reduced ability to resolve inflammation.

· Loss of control over inflammation: As we age, the body's innate immune system becomes chronically overstimulated. This process is called immunosenescence. As a result, pro-inflammatory cytokines are released more frequently, leading to a state of persistent inflammation. This loss of regulatory control contributes to the onset of various chronic diseases, including cardiovascular disease, diabetes, and neurodegenerative disorders.

· Genetic, epigenetic, and metabolic dysfunction: These dysfunctions occur in different cell types and organs. Ageing affects the expression of genes responsible for inflammation and immune responses. Genetic factors can predispose individuals to higher levels of inflammation. Epigenetic changes, which involve DNA modifications affecting gene expression without altering the genetic code, may also play a role. Metabolic dysfunctions, such as insulin resistance and mitochondrial dysfunction, can further exacerbate inflammation by promoting the release of inflammatory mediators from various cell types and organs.

· Gut microbiota: The gut microbiota can release inflammatory products and contribute to 'inflammageing'. The gut microbiome, made up of trillions of microorganisms residing in the digestive tract, plays a crucial role in maintaining immune balance. Ageing can lead to changes in the composition and diversity of gut microbiota, often resulting in dysbiosis (an imbalance in microbial populations). This can lead to the production of harmful metabolites and inflammatory products that enter the bloodstream, contributing to systemic inflammation. 

What are the effects of 'inflammageing'?

·  'Inflammageing' is a contributing, independent and significant risk factor for morbidity and mortality in the elderly. 

· It can contribute to the onset and progression of age-related diseases, such as Alzheimer's disease, arthritis, cancer, heart disease, and type 2 diabetes. 

· It manifests itself by chronic fatigue: persistent feelings of tiredness and low energy levels may be linked to the ongoing inflammatory processes in the body. Inflammation can impair mitochondrial function, affecting energy production and leading to fatigue and malaise.

· Arthralgias are common: inflammation can affect the joints. 

· Pain, stiffness and reduced mobility may be indicative of inflammageing.

(Long) Covid as an example of ‘inflammageing’ exacerbating the neuro-inflammation 

Advanced age is one of the main determinants of the mortality risk associated with coronavirus 2019 (COVID-19) and its long-term complications, such as Long Covid.

Long Covid is characterized by prolonged symptoms following an acute COVID-19 infection and has emerged as a significant public health concern. 

Based on the latest data available for 2023, the prevalence of Long Covid is estimated to range between 10% and 50% of those infected, depending on the population studied, access to healthcare, vaccination rates and public health measures. Studies conducted in North America indicate that 10-30% of COVID-19 survivors have symptoms of Long Covid, a proportion similar to that observed in Europe.

In March 2022, a study published in Nature provided important insights into the neurological effects of COVID-19 based on imaging studies. The research involved 800 people aged 50 and over, half of whom had contracted the virus, undergoing pre- and post-pandemic brain scans. The results showed that those who had contracted the virus exhibited brain shrinkage (loss of grey matter), altered brain structure and accelerated ageing, as if these patients had aged 10 years in just a few weeks. The volumetric reduction suggests that the virus may lead to neuroinflammation and other neurodegenerative processes with a long-term impact on brain health. As a result, individuals may experience cognitive decline, manifesting as memory and attention problems, often referred to as “brain fog”.

One of the underlying mechanisms that may contribute significantly to the virus-induced neuroinflammation is ‘inflammageing’. It involves both dynamic remodeling of the immune system, known as immunosenescence and chronic low-grade systemic inflammation. 

Research highlights the necessity of monitoring neurological health of individuals recovering from COVID-19, as the virus may have far-reaching implications, including an increased incidence of cognitive deficits and a rising incidence of dementia.

How to manage 'inflammageing'?

There are three ways to reduce inflammageing: 

Diet:  an anti-inflammatory diet can help manage inflammageing. It includes foods rich in antioxidants and polyphenols, such as wholegrain cereals, vegetables, fruit, nuts and fish. Foods to avoid include: refined carbohydrates, such as white bread and pastries, high fat dairy, fried foods, red and processed meats.

Exercise: A large body of research has also looked at the link between physical activity and inflammation. A 2020 study suggests that regular exercise is a natural anti-inflammatory agent that can prevent or delay chronic inflammation as you age. The Center for Disease Control (CDC) recommends that older adults strive to get at least 2.5 hours of moderate-intensity exercise per week, plus muscle-strengthening activities at least 2 days per week.
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Managing stress can help tamp down inflammageing. Chronic stress may trigger the “fight or flight” response, causing the body to release pro-inflammatory cytokines (small proteins) that promote inflammation throughout the body. A few stress-reduction activities to try: Practicing mindfulness: turning down the volume and focusing on your senses or walking mindfully, spending time with supportive loved ones, engaging in pleasurable activities, focusing on deep breathing. 

Final thoughts

‘Inflammageing’ is a new feature of ageing that requires understanding and proactive measures to limit its negative effects. The relationship between Long Covid and inflammageing highlights how chronic inflammation can be damaging and predispose individuals to prolonged illness. 

Ongoing research is essential to elucidate the mechanisms involved and develop effective treatments.