The immune response, inflammation and aging
We are exposed to a range of foreign substances every day. Some of these are potentially harmful and are therefore rapidly identified and removed by our immune defense systems. At the same time, we don’t dispose of our own tissues, which we identify as belonging to us (a good guard dog does not bite its own master, just the burglars).
One of the many effects of immuno-senscence and inflamm-aging is that this system of self-tolerance is slowly eroded. Instead of only reacting against toxic invaders like 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, lupus, pulmonary fibrosis, the antiphospholipid syndrome and thyroiditis.
How can I measure inflammation associated with aging?
There are a number of tests available to identify individuals with chronic inflammation:
- We can measure levels of proteins released by the liver 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 the development of disease and disability with age. For example, individuals with CRP concentrations greater than 3.0 mg/L are more likely to go on to have a heart attack or develop dementia or some cancers than those with a level below 1.0 mg/L (low risk).
- It is possible to measure circulating levels of cytokines, the chemical messages that trigger inflammation. For example, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) are elevated in elderly individuals.
- During our lives, we are all exposed to viruses that remain dormant within us, held in check by immune defences. Testing the integrity of these defences enables us to tell how well they are doing their job. If immune function is reduced due to stress or ageing, this can lead to signs that one such virus, known as cytomegalovirus (CMV), is waking up in our body (measured by anti-CMV antibodies).
- Finally, it is possible to measure levels of circulating inflammatory cells. Elevated levels of white cells in circulation indicate increased levels of inflammation and higher levels of risk. Measurement of various white cell populations is also possible, which provides more detailed information on specific functions of the immune system.
Which marker of inflammation is the best one?
While high levels of any of these markers have been associated with an increased risk for adverse outcomes in a range of settings, the advantage of one type of measurement over another remains to be established. 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. Increased levels of inflammatory signals should be considered a warning sign that more work is needed to prevent bad things from happening. Moreover, dealing with all the other risks for 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, as their absolute risk is greater.
There is currently little information about the value of directly treating the immune defense system. While decreasing chronic inflammation would seem to be important, there are potential dangers in blocking processes vital for tissue repair and defense against infections. Nonetheless, a number of simple activities have been shown to safely turn down the flame of inflammation. Indeed, all of the very diverse interventions detailed in this book will have some anti-inflammatory effects. This is because the innate immune system is non-specific, responding generically to any hazard. The simplest way to reduce inflammation is not to unnecessarily feed the fire.