Some of the aches, pains and diseases we suffer as we get older may be due to age-related inflammation - or "inflammaging". Photo / Getty Images
This “chronic, smouldering low-grade inflammation” as one researcher described it, is associated with many health issues.
As we age, we tend to have more aches, pains and diseases. Researchers believe that some of these may be related to persistent inflammation.
They call it “inflammaging” – age-related inflammation, which is present even in the absence of injury or illness.
It is considered a hallmark of ageing and is characterised by a “chronic, smouldering low-grade inflammation,” said Vishwa Deep Dixit, a professor of pathology and immunobiology and the director of the Yale Centre for Research on Ageing.
This chronic smouldering is unfortunately associated with a host of health issues, but new research suggests that not everyone may experience inflammaging. Some Indigenous people don’t seem to get inflammaging at all compared with people in industrialised countries.
Either way, researchers are studying how to curb this type of inflammation to stave off its health effects.
Inflammaging “sets up the environment” for potential neurodegenerative diseases such as dementia or Parkinson’s, said Juan Pablo de Rivero Vaccari, an associate professor of neurological surgery at the University of Miami’s Miller School of Medicine who has been studying the immune response for 20 years.
Understanding inflammaging is crucial for understanding the biology of ageing and what we “can do to stall the degenerative diseases that emerge from inflammaging,” Dixit said.
Normally, inflammation is important to our bodies mounting an immune defence when we get an infection or injury and shutting off when the threat passes.
With inflammaging, however, inflammation persists even when there is no infection to fight. (“The purpose of this inflammation is actually still unclear,” Dixit said.)
A major source of the smouldering, inflammatory signals seems to be stressed out, damaged cells that release proteins indicating “something is not going well,” said Alan Cohen, an associate professor of environmental health sciences at Columbia University’s Mailman School of Public Health.
“As we age, our internal stressors increase. This is more or less inevitable. Something is not going well. In any species that ages, something is not functioning as well with age,” he said.
Inflammaging has been strongly associated with several age-related health conditions, including atherosclerosis, cardiovascular diseases, diabetes, frailty, dementia and death.
It may be the “predecessor” for many of these diseases, Vaccari said.
For example, Alzheimer’s disease – the most common type of dementia – is believed to start up to 20 years before cognitive changes become apparent, and there is growing evidence that an underlying inflammatory response is already present during this time, Vaccari said.
Known risk factors for inflammaging include increased visceral fat, which wraps around internal organs, and uncontrolled blood sugar levels, Vaccari said.
Inflammaging is “really strongly associated with a lot of bad outcomes, so we know, in general, that you’re probably better off if you don’t end up with a very high level of inflammation as you get older,” Cohen said.
Researchers are working on unravelling the specific mechanisms of inflammaging for earlier diagnosis and more targeted treatment.
Studies have found that specific cytokines – proteins secreted by cells that coordinate immune and inflammatory responses – such as IL-6 and IL-1β, are consistently implicated in inflammaging.
“Moving forward, what is really going to be exciting is for us to understand which one of these pathways are adaptive and which ones are maladaptive,” Dixit said.
In a recent study, Cohen and his colleagues found that inflammaging – at least as it is commonly measured with cytokines – is not universal, and seems to correspond with an industrialised lifestyle.
Researchers compared immune marker data from people living in two industrialised countries, Italy and Singapore, with data from Indigenous people living in two non-industrialised regions, the Tsimane of the Bolivian Amazon and the Orang Asli of parts of Malaysia.
Among the Italians and Singaporeans, the inflammaging factors generally matched and were associated with age and chronic age-related diseases such as chronic kidney disease.
But when the researchers looked at the Tsimane and Orang Asli, neither population followed the inflammaging pattern as people from the industrialised countries as they got older. They also did not have the profile of chronic diseases that normally crops up with age in industrialised countries.
“It really became clear that they’re not doing anything like what the industrialised populations are doing,” said Cohen, who was the senior author of the study.
This wasn’t to say that the people from non-industrialised regions did not have inflammation. On the contrary, for the Tsimane in Bolivia, inflammation stayed high throughout their lives, probably because of common infections. Roughly 66% of Tsimane have at least one intestinal parasitic infection, while 70% of Orang Asli have a prevalent infection, including respiratory and fungal, at any given time.
And among Italians and Singaporeans, the inflammaging patterns weren’t exactly the same. The cytokine IL-6, which is often considered a key indicator of inflammaging, did not correlate with age in the Singaporean population.
There may be underlying commonalities to immune ageing, but how they manifest may depend on the context, said Cohen, who wrote a recent review.
“We should not think of inflammation as a problem in and of itself,” said Cohen, who likens it to a fire alarm.
The fire alarm may not be pleasant, but often it indicates that something isn’t going well in the building, he said. But “none of this means you don’t want the fire alarm system installed or that you want to deactivate it,” Cohen said.
A healthier lifestyle in your younger years will benefit you in your older years.
“Life is interesting in that sometimes it starts sending you a bill for the things you did 20 years earlier,” Vaccari said.
Older people who already have high inflammation could adopt more targeted approaches to address the root causes of inflammation, Cohen said.
Controlling blood pressure, reducing visceral fat and managing blood sugar levels “would go the longest way possible for a healthy lifestyle,” Vaccari said.
There is wisdom in following “the same thing that your grandma and my grandma said, which is: ‘Do things in moderation, don’t eat too much, and exercise more,’” Dixit said.
There is not enough evidence to recommend a particular diet, Dixit said, but managing caloric intake may be helpful because caloric restriction is linked to longevity and health. In a recent preprint study, which has not been peer-reviewed yet, Dixit and his colleagues reported that reducing caloric intake by 14% could reduce a key immune marker important to inflammation.
Stay nourished, but “it doesn’t hurt every now and then to feel hungry,” Vaccari said.
Don’t take sleep for granted because it “helps the brain get rid of toxins,” he added.
At the same time, don’t become overly anxious about inflammaging itself because that means “you’re probably trying to micromanage something where we don’t have enough knowledge to micromanage it well,” Cohen said.
Instead, “enjoyment is actually also part of the health benefit,” he said. “If you are suffering to make yourself live longer, I don’t know that that actually helps you that much.”