Inflammation and its effects on aging

Inflammation is designed to be protective, but in the wrong place and at the wrong time it can be destructive, so we have outlined how it affects aging and how to identify signs of inflammation in your body.

Our bodies have many defense and healing mechanisms that are designed to quickly turn on when confronted by something harmful, such as toxins, trauma or infection.

An example of this kind of defense system is inflammation. We all need inflammation at certain times to fight infection or heal wounds. Left unchecked, however, inflammation can lead to collateral damage and disease.

Aging is associated with a number of changes in the immune defense system, cumulatively known as ‘inflamm-aging’.

More than simply being a marker of harmful processes occurring, unfettered inflammation is a significant element of aging. Chronic inflammation, for example, can accelerate bone density and cognitive function, and destabilize the lining of blood vessels, contributing to heart attacks and strokes.

Here we look at changes in the immune defense system in the aging body, and some of the ways these pathways can be manipulated to our advantage.

Your immune system

The immune system is an inherent self-defense mechanism that helps the body differentiate healthy body cells from ‘non-self’ molecules such as disease-causing organisms (bacteria and viruses, cancerous cells, fungi and parasites).

It has many specialized units that work in concert to win our battles.

These can be broadly divided into two arms: the innate and adaptive immune systems. The innate system provides an immediate, aggressive but generic response when it recognizes anything harmful going on. It is composed of both cells and chemical components, which trigger inflammation.

By contrast, the adaptive immune response reacts more slowly, is tailored to specific invaders, and is triggered by specific recognition molecules, the best known being antibodies. This response is used in vaccinations, which adapt our immune system to better defend against specific invaders.

Both innate and adaptive systems continuously talk to each other to form a defense strategy and ensure a speedy recovery.

As we get older, regulation of the innate immune system can become dysfunctional, resulting in chronic low-grade inflammation. At the same time, there is a steady decline in adaptive immunity (known as immuno-senescence). This results in a decreased response to vaccines and increased risk of infections, cancer and other diseases.

One of the many effects of immuno-senescence and inflamm-aging is that instead of only reacting against harmful invaders such as bacteria, the immune response in aging individuals sometimes turns on itself, so we essentially beat ourselves up.

A number of diseases associated with aging are examples of this loss of self-tolerance, including rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, pulmonary fibrosis, antiphospholipid syndrome and autoimmune thyroiditis.

How does inflammation cause damage?

Scarring

Although designed to be protective, inflammation in the wrong place and at the wrong time can be destructive to tissues and have a number of adverse effects on your health.

An example of this is the process of scarring. Scars are the result of inflammatory signals that remodel tissues to wall off damaged areas.

While this is helpful to hold our wounds together, scar tissue is not the same as the tissue it replaces and usually results in some compromise of function. Excessive scarring in the lungs, blood vessels or heart, for example, leaves them stiff and dysfunctional.

Free radical production

Inflammation is also a major producer of free radicals, which the immune system uses to kill off invading bacteria or get rid of damaged cells.

Free radical damage is rather indiscriminate, however, and results in collateral damage if left firing away.

Although the damage may initially be small, if it continues it can accumulate and eventually wear us down. Cancer, for example, is more common in areas of chronic inflammation due to cumulative DNA damage, particularly if the adaptive immunity that keeps cancers in check is also in decline.

Perpetuate disease

Inflammation can also perpetuate disease processes, including heart disease, diabetes, Alzheimer’s disease, arthritis, osteoporosis and some cancers, which share a common inflammatory component.

In Alzheimer’s disease, for example, accumulating brain damage triggers inflammation, which perpetuates further injury. Inflammation is also central to atherosclerosis – the process that ultimately leads to heart attacks and strokes.

Because inflammation is a generic process, anything that enhances it will affect a range of conditions. Essentially, anything that fuels the fire will make the flame burn stronger.

Release of cytokines

While local inflammation can lead to local problems, its effects can also be widespread, affecting other tissues even if they aren’t damaged themselves.

This occurs due to the release of inflammatory cytokines, signaling molecules that not only trigger inflammation, but also communicate their effects to all corners of the body.

For example, over-stuffed fat cells that release cytokines can render distant cells resistant to the effects of insulin, contributing to glucose intolerance and diabetes. In the same way, joint inflammation may increase the risk of heart disease and stroke via the cytokines that are released.

Depression also appears to be partly triggered by inflammatory cytokines, which is why we feel low when we are sick with the flu.

Inflammatory signals can also be directly damaging. For example, some circulating cytokines kill nerve cells of the brain, potentially contributing to cognitive decline, which is exaggerated in those with chronic inflammation.

Signs of inflammation in your body

There are a number of ways to identify signs of inflammation in your body.

You can measure levels of proteins the liver releases into the circulation in response to inflammatory signals (known as acute-phase proteins). The best known of these are C-reactive protein (CRP), fibrinogen, soluble intercellular adhesion molecule-1, soluble CD40 ligand, neopterin and serum amyloid A.

In general, high levels of proteins in the bloodstream are associated with disease development and disability.

For example, individuals with CRP concentrations greater than 3 mg/L (increased risk) are more likely to have a heart attack or develop dementia or some cancers than those with a level below 1 mg/L (low risk).

Measuring circulating levels of cytokines is another way to identify signs of inflammation in your body. Interleukin-6 and tumor necrosis factor-alpha, for example, are elevated in elderly people.

During our lives, we are all exposed to viruses that remain dormant within us, held in check by immune defenses. Testing the integrity of immune defenses enables us to determine how well they are doing their job.

For example, signs that cytomegalovirus (CMV) is active in our body (as demonstrated by elevated levels of anti-CMV antibodies) is associated with reduced immune function.

Finally, you can measure levels of circulating inflammatory cells to determine signs of inflammation in your body. Elevated levels of white cells in circulation indicate increased levels of inflammation and higher levels of risk.

It is also possible to measure various white cell populations, which provide more detailed information on specific immune system functions.

Which marker of inflammation is the best one?

High levels of any of these markers have been associated with an increased risk for adverse outcomes. But experts are yet to establish the advantage of one type of measurement over another.

It is likely that a set of inflammatory bio-markers will provide the best discriminating power, particularly combined with other markers of risk.

However, any value in measuring our inflammation levels comes if we do something when we get the result. If we and our health care provider have no plans, or plan to undertake activities regardless of the result, then spending on expensive tests offers us very little.

How can I reduce inflammation associated with aging?

Elevated markers of inflammation identify an individual at increased risk of disease, disability and premature mortality. You should consider increased levels of inflammatory signals as a warning sign to do more.

Moreover, dealing with all the other risks of aging is more beneficial in absolute terms in those with high levels of inflammation, as they have the greatest absolute risk.

For example, in individuals with high levels of inflammation, lowering LDL (bad) cholesterol or systolic blood pressure may be more beneficial than for those with lower levels of inflammation, as their absolute risk is greater.

The simplest way to reduce inflammation is not to unnecessarily feed the fire.

 

Last reviewed 31/Mar/2017

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