Short term inflammation is a vital part of the immune response, necessary to keep us healthy in the face of life's many slings and arrows. Chronic inflammation is a different story, however, as it is a potent source of damage to tissues and bodily systems over the course of a lifetime. Numerous research groups are focused on developing a better understanding of how and why rising levels of chronic inflammation goes hand in hand with aging and dysfunction of the immune system. They see this as a characteristic process of degenerative aging, and in recent years have taken to calling it inflammaging.
To pick one example of the mechanisms involved in inflammaging, chronic inflammation is one important factor in the correlation between more visceral fat tissue, shorter life expectancy, and higher risk of suffering all of the common age-related diseases. Visceral fat is metabolically active and its interaction with immune cells is unhealthy, causing inflammation. That has meaningful consequences for health and mortality if you happen to carry a lot of fat tissue around with you.
Fat or no fat, the immune system becomes steadily more dysfunctional with age, however. The fat just makes it worse. An aged immune system is less effective at its tasks of defense and elimination of potentially dangerous damaged cells, but also overactive at the same time, fallen into a state of chronic inflammation in its disarray. The recently published research quoted below suggests that increased inflammation is such an important component of this degenerative process that even very crude tools that suppress inflammation can provide benefits. This suggests that more sophisticated approaches may also be worth pursuing even through they would most likely be only stepping stones on the way to real immune rejuvenation. Present means of suppressing age-related chronic inflammation don't address the root causes, the damage and misconfiguration of the aged immune system. Future treatments that tackle root causes should be far more effective.
The researchers compared lung cells from old and young mice and found that in the old mice, genes that make three classic pro-inflammatory proteins, called cytokines, were more active in the lungs of old mice. The cytokines are interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a). In addition, immune system cells called macrophages in the lungs from old mice were in an advanced state of readiness to fight an infection - a status that signals inflammation. Macrophages in young mouse lungs were in a normal, resting state.
In test tubes, the scientists exposed mouse lung macrophages to tuberculosis (TB) bacteria. The macrophages from old mouse lungs were quicker to absorb the bacteria than were immune cells from young mice, but that initial robust immune response from the cells of old mice could not be sustained. "A primed macrophage in an old mouse has lots of receptors on its surface that can bind to TB, taking it up and trying to kill it. But what it lacks is the ability to increase the response further. A resting macrophage in a young mouse takes up TB and then can be activated to do something even more effective at killing the bacteria."
Though some elements of the elderly response to TB remain a mystery, this finding suggested that the inflammation in the lungs of elderly mice had the direct effect of reducing the long-term effectiveness of their immune response to TB infection. The researchers gave old and young mice ibuprofen in their food for two weeks and then examined their lung cells. After this diet modification, several pro-inflammatory cytokines in the lungs of old mice had been reduced to levels identical to those in the lungs of young mice, and the macrophages in old mouse lungs were no longer in a primed state. "There's a trend toward reduced inflammation. Essentially, ibuprofen made the lungs of old mice look young. Putting young mice on ibuprofen had no effect because they had no lung inflammation, which implies the ibuprofen reduced the inflammation and changed the immune response in the old mice."
Systemic inflammation that occurs with increasing age (inflammaging) is thought to contribute to the increased susceptibility of the elderly to several disease states. The elderly are at significant risk for developing pulmonary disorders and infectious diseases, but the contribution of inflammation in the pulmonary environment has received little attention.
In this study, we demonstrate that the lungs of old mice have elevated levels of proinflammatory cytokines and a resident population of highly activated pulmonary macrophages that are refractory to further activation by IFN-γ. The impact of this inflammatory state on macrophage function was determined in vitro in response to infection with Mycobacterium tuberculosis (M.tb). Macrophages from the lungs of old mice secreted more proinflammatory cytokines in response to M.tb infection than similar cells from young mice and also demonstrated enhanced M.tb uptake and P-L fusion.
Supplementation of mouse chow with the NSAID ibuprofen led to a reversal of lung and macrophage inflammatory signatures. These data indicate that the pulmonary environment becomes inflammatory with increasing age and that this inflammatory environment can be reversed with ibuprofen.