Causes of inflammaging
One source of inflammaging could come from cellular debris that builds up with aging, coupled with a weakened ability to eliminate it. Just as the failure to throw out trash in a home will lead to the growth of pathogens, the accumulation of cellular debris sets off a dangerous reaction leading to chronic activation of the innate immune system. Other sources of inflammaging could come from harmful microbes in the mouth or gut that leak into surrounding tissues or the bloodstream, and infectious agents the immune system is unable to overcome. Inflammaging will also be induced by cellular senescence. Senescent cells have come to the end of the road but instead of dying, they persist, pumping out inflammatory molecules, causing considerable damage to surrounding tissue. Another possible reason comes from adverse changes to the immune system itself with aging (immunosenescence), leading to mild immune hyperactivity. One part of a cell plays a major role in inflammaging and is also a hallmark of aging itself. It’s here that scientists made their breakthrough.Faulty calcium signaling
Dysfunction in the cells’ energy factories – the mitochondria - has long been linked to inflammaging, but the underlying mechanisms behind it were not understood. Immune cells called macrophages also become less effective with aging, but the reasons for this were also unclear. Now researchers from the University of Virginia (UVA) have pinpointed the precise molecular machinery involved in both processes. The driver of inflammaging is improper calcium signaling in the mitochondria of macrophages. The mitochondria rely heavily on calcium signaling but the researchers discovered macrophages lose their ability to take up and use calcium with age and this inability means they can’t provide an effective response, giving rise to chronic inflammation. By finding a way to increase calcium uptake in mitochondrial macrophages, damaging inflammation could be prevented. Since these immune cells reside in all organs, including the brain, targeting such “tissue-resident macrophages” could slow down the diseases of aging, including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. “I think we have made a key conceptual breakthrough in understanding the molecular underpinnings of age-associated inflammation,” said Bimal Desai, who led the research team. He believes the discovery will lead to new therapeutic strategies to intercept and prevent the process that lies at the heart of so many aging processes.Likely applies to other immune cells
The research kills two birds with one stone because it not only provides an explanation for why mitochondria are linked to inflammation but also identifies a “keystone” mechanism responsible for age-related changes in the macrophages. The job of these immune cells is to remove cellular debris by engulfing and swallowing up dead and dying cells. They also patrol for invaders and call on other immune cells as needed. Age-related changes will therefore, even at the best of times, lead to low grade inflammation. But when confronted by tissue damage or an invader, they can become hyperactive, which drives inflammaging. The UVA team suspect improper calcium signaling applies in many other immune cells. As a result, stimulating calcium uptake across all of them would potentially give the immune system a major boost. The team intends to continue their research and look for an effective therapy to fight inflammation, however, you don’t have to wait. There’s plenty you can do now to ward off inflammaging.How to extinguish the fires of inflammation
One of the best ways to stop inflammation in its tracks is to lead an anti-inflammatory lifestyle. It starts with your diet. The Mediterranean diet, the MIND diet, the Green Med diet, even the Longevity diet—all of which we’ve written about in the past—can help you stop inflammation. Also, make sure you’re getting regular exercise, managing stress and sleeping well at night. Finally, the new research points to additional ways you can slow down the mechanism that results in inflammaging. First of all, the process of emptying out the cells’ trash is called autophagy. You can improve this process with intermittent fasting such as eating all meals within a 12 to 16-hour window, giving the cells plenty of time to detoxify and deal with their waste. To prevent leakage of harmful microbes into the mouth, brush and floss the teeth daily and have regular dental checkups to prevent gum disease. To keep the gut microbes in a healthy balance, add traditionally fermented and cultured food to your diet such as yogurt, kefir, kimchi, sauerkraut, and olives. It’s also a good idea to take a probiotic supplement. In addition, antioxidant flavonoids are effective at fighting cellular senescence, so a diet high in fruits, especially citrus fruits, as well as vegetables, herbs, and spices will be of considerable help. Best Regards, The Aging Defeated TeamChronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases (2014) https://academic.oup.com/biomedgerontology/article/69/Suppl_1/S4/587037
Reduced mitochondrial calcium uptake in macrophages is a major driver of inflammaging (2023) https://www.nature.com/articles/s43587-023-00436-8
