Age-Related Inflammation

LIFESTYLE CHOICES CAN HELP.

When you hear the word “inflammation” you may initially think it sounds like a bad thing, but acute inflammation is actually a healthy, positive defence mechanism. It is the body’s response to infection, damage, or injury, and it activates the immune system to trigger the healing process. The key word there is “acute,” which refers to a severe and sudden response, but one that is short term and temporary.

In contrast, chronic inflammation occurs when there is ongoing, excessive activation of immune cells. This type of long-term exposure to inflammation is linked with myriad  negative impacts on health.

Chronic inflammation can occur at any age, but “inflammaging” is a specific type of chronic inflammation that affects older adults.

It is chronic, low-grade inflammation throughout the body that occurs as one ages, in the absence of infection, damage, or injury. This pro-inflammatory state is characterized by elevated levels of inflammatory markers in the blood.

Research has found that inflammaging is linked with an increased risk of a variety of common age-related diseases, including cardiovascular disease, cancer, chronic kidney disease, neurodegenerative diseases, osteoarthritis, and depression, as well as adverse health outcomes such as disability, frailty, and premature death.

In this article, we focus on how inflammaging impacts neurodegeneration, and the steps you can take to delay or decrease inflammaging as you age to help you keep your brain healthy longer.

INFLAMMAGING & NEURODEGENERATION

Inflammaging has been shown to play a key role in the development of cognitive impairment and neurodegenerative diseases in aging individuals. There are many theories about why this happens. One potential explanation is that chronic inflammation appears to hinder the body’s processes for cleaning up cell debris, at a time when more cells are being damaged and dying off due to aging.

Another is that inflammatory compounds cross the blood-brain barrier, contributing to negative effects such as atrophy of the hippocampus and increased oxidative stress (an imbalance of free radicals and antioxidants, leading to cell damage).

There is likely a complex interaction of factors going on because inflammaging is also linked directly with the development of chronic age-related diseases like atherosclerosis, metabolic syndrome, and Type 2 diabetes (which are known risk factors for dementia).

A 2022 review by Mx. Alexandra V. Sentyabreva and colleagues – published in Brain Sciences – looked at the research evidence to date about the connections between inflammaging and Alzheimer's disease, in particular.

“Our review disclosed that there is growing evidence of the relationship between Alzheimer's disease and chronic inflammatory diseases, as well as between Alzheimer’s disease and age-related inflammation, i.e., inflammaging,” said Mx. Sentyabreva, a PhD student and researcher at the Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery in Russia.

“Some researchers consider inflammation the initial mechanism of neurodegeneration in Alzheimer’s disease, believing that it is both a triggering and aggravating factor in the formation and accumulation of amyloid-beta plaques and tau tangles associated with the disease,” explained Mx. Sentyabreva.

“It’s not yet clear whether inflammation is indeed the initial mechanism, but there is ample evidence that inflammation clearly plays some role in Alzheimer’s disease.”

“However, it’s important to note that all people develop inflammaging as they age, yet not everyone develops neurodegenerative diseases,” continued Mx. Sentyabreva. “That indicates that the inflammatory process is not enough on its own to lead to neurodegeneration. More research is needed to determine how the multiplicity of variables interact.”

TIPS TO HELP REDUCE INFLAMMAGING

Inflammaging varies across individuals, and its presence does not automatically lead to disease. Studies of centenarians – including one by Dr. Paola Lucia Minciullo and colleagues, published in Archivum Immunologiae et Therapiae Experimentalis in 2015 – have found that these long-lived people have markers of low-grade inflammation, just as most older adults do, but that inflammation is counterbalanced by the presence of anti-inflammatory molecules.

This suggests that greater longevity and healthy aging does not require the absence of inflammation, but rather a mix of pro-inflammatory and anti-inflammatory processes that balance each other out.

So, while inflammaging may be impossible to avoid completely, there are steps you can take to offset its effects as you age. Below are some evidence-based, lifestyle tips to help reduce inflammaging and its many negative impacts on health.

MOVE MORE

Living a sedentary lifestyle is associated with higher levels of inflammation markers in older adults, so moving more is key to helping keep inflammaging in check. And  research suggests that the benefit of exercising for reducing inflammation is not contingent on losing weight.

“While it is widely agreed that physical activity is an effective anti-inflammatory intervention, there is currently no consensus about the recommended exercise intensity and duration for optimal effect,” said Dr. Niharika Duggal, an assistant professor at the University of Birmingham in the U.K. and one of the authors of the 2023 review “Inflammaging as a Target for Healthy Ageing” in Age and Ageing

“As far as what type of physical activity is best, research has found that both cardiovascular (aerobic) exercise and resistance training have an anti-inflammatory effect if done regularly at moderate intensity. However, it’s likely that all types of movement can help since prolonged periods of inactivity have been recognized as having pro-inflammatory effects, possibly due to weight gain and accumulation of visceral fat,” continued Dr. Duggal. “Most importantly, it’s never too late to start incorporating exercise and breaking up long periods of sitting.”

EAT A HEALTHY DIET

What you eat, and don’t eat, can have a direct impact on inflammation. Following the Mediterranean diet – which emphasizes high consumption of fruits and vegetables (including leafy greens), legumes, nuts, olive oil, and fish, and low consumption of red meat, dairy, and saturated fat – has a number of health benefits, including reduced inflammation.

“Eat a variety of fruits and vegetables of different colours to modulate the gut microbiota by promoting the growth of beneficial bacteria that produce anti-inflammatory short-chain fatty acids. However, try to eat certain fruits often since they are known to contain phytochemicals with protective anti-inflammatory and antioxidant properties, namely, blueberries, pomegranate, tomato, and watermelon.”  

“Green tea and curcumin have also been found to have anti-inflammatory properties, so consider adding those to your diet as well,” continued Dr. Duggal.

 What should you avoid, or minimize, eating? Ultra-processed foods. They are calorie-dense and low in fibre and nutrients, contain artificial ingredients, and tend to be high in salt, sugar, and trans fats. A diet high in these types of food (i.e., packaged snacks, frozen meals, and sugary drinks) is associated with an increased risk of inflammation (as well as with the many diseases and disorders that are linked to inflammation such as obesity).  

MANAGE STRESS

 “Managing stress helps combat inflammaging by reducing cortisol, a hormone that encourages the storage of visceral fat,” explained Dr. Duggal. (Visceral fat, which is a known factor in chronic pro-inflammatory responses, is not always visible from outside the body since it found around the internal organs.)

“There are many ways to relieve stress, including exercise, time spent in nature, meditation, socializing with others, and getting enough sleep,” continued Dr. Duggal, “so choose whatever activities you enjoy most.”

GET ENOUGH GOOD-QUALITY SLEEP

Chronic insufficient sleep is linked with inflammation and negative health effects including metabolic syndrome and cardiovascular disease (which are themselves associated with increased levels of pro-inflammatory markers in the body). On the other hand, good sleep provides long-lasting immunoenhancing effects.

Sleep is so important in part because of its relationship with stress. “Sleep disturbances can lead to dysregulation of the HPA axis, resulting in altered cortisol secretion,” explained Dr. Duggal. (The HPA axis is the communication system between the hypothalamus, the pituitary gland, and the adrenal glands. It plays a major role in stress management.)

Although not everyone experiences problems with sleep as they age, many people do, frequently indicating difficulties falling or staying asleep for example. This type of poor sleep with age can exacerbate inflammaging.

Exercising regularly is one of the best ways to improve sleep at any age, along with good sleep hygiene habits, i.e., things like going to bed at the same time each night, keeping your bedroom dark and cool, and turning off all screened devices at least an hour before bed.

CONNECT WITH OTHERS

There is an abundance of research showing links between systemic inflammation and negative emotional states (including loneliness).

Emerging evidence suggests that loneliness may be a driving factor in the link between stress and inflammation.

Collectively, these findings emphasize how important it is to address loneliness, not just because it feels better emotionally to be connected with others in meaningful ways but also because doing so supports our physical health.

TAKE SUPPLEMENTS

“You might also want to consider taking supplements that have shown potential to reduce inflammation,” said Dr. Duggal. “Those include Omega-3 polyunsaturated fatty acids, resveratrol, vitamins C and D, magnesium, and probiotics.”

(Note that curcumin, mentioned in the healthy diet tip because it can be used as a spice in cooking, is also available as a supplement.) Be sure to consult with your health provider for guidance about which supplements to take and in what dosage, as what is recommended will vary by individual.

It’s interesting, but not surprising, that this list of tips mirrors most of the Six Pillars of Brain Health: Exercise, Nutrition, Social Activity, Stress Management, and Sleep. (The only pillar that is missing is Mental Stimulation.) For detailed information about the six pillars, check out the article “Do You Know Your Six Pillars of Brain Health? Reduce Your Dementia Risk Through Your Lifestyle Choices” in Mind Over Matter® magazine volume 15, which you can read at womensbrainhealth.org/mind-over-matter-magazine.

Inflammation is clearly one of the underlying mechanisms that affects brain health. Taking steps to reduce inflammation will support not just your brain health, but the health of all the systems in your body.

“As scientists continue their research into inflammaging, it’s possible that they may discover a medication that will help stop, reverse, or delay this age-related inflammation,” said Dr. Duggal. “In the meantime, though, isn’t it great to know there is so much you can do in terms of lifestyle factors to help stave off inflammaging and keep your brain as healthy as possible as you get older.”

SEX DIFFERENCES IN INFLAMMAGING

The immune systems of women and men differ, however the sex-specific distinctions change over their lifespan.

There are pre-existing differences in immunity between women and men when they are young, but then those differences shift as menopause and andropause unfold.

A 2023 paper by Dr. Fabiola Olivieri and colleagues reviewed sex-dependent differences related to inflammaging and found they are affected by hormones. In particular, they reported that women have an immune system advantage over men during their reproductive years, but reduced estrogen production post-menopause is associated with immune system changes that eliminate that advantage.

As a result, women tend to live longer but experience worse health in later life compared to men. (These findings were shared in Mechanisms of Ageing and Development.)

Source: Mind Over Matter V19

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