Changes in the immune system can promote healthy aging
July 10, 2020
Science Daily/Max-Planck-Gesellschaft
As we age, the immune system gradually becomes impaired. One aspect of this impairment is chronic inflammation in the elderly, which means that the immune system is constantly active and sends out inflammatory substances. Such chronic inflammation is associated with multiple age-related diseases including arthritis and Alzheimer's disease, and impaired immune responses to infection. One of the questions in ageing research is whether chronic inflammation is a cause of ageing, or a consequence of the ageing process itself? Scientists in the laboratory of Director Adam Antebi at the Max Planck Institute for Biology of Ageing in Cologne, Germany have found evidence suggesting that increased inflammation causes the ageing process to speed up, and that there is a fine balance between maintaining immune system function and longevity.
From their work in the tiny roundworm, Caenorhabditis elegans, the scientists discovered a change in an evolutionarily conserved gene called PUF60, which made the worms long lived but at the same time dampened the immune response. Worms with this change lived about 20% longer than normal worms, but when they were infected with certain bacteria, they succumbed more quickly to the infection. This means that an overactive immune system also has a price: it shortens life span. Conversely, a less active immune system pays off as longer life span -- as long as the animal does not die from an infection.
How does PUF60 regulate this fine balance between a maintained immune system and longevity? PUF60 works as a so-called "splicing factor," and is involved in the removal (or "splicing out") of segments in the ribonucleic acid, RNA. This process is essential to generate functional proteins.
The scientists found that the genetically changed PUF60 perturbs this process and alters the regulation of other genes that are involved in immune functions. "We're excited by this finding because it implicates a very fundamental process in the cell to immunity," says Adam Antebi. "These observations of course raise further questions. Notably pinpointing how PUF60 activity affects immunity and longevity, and how these two processes are balanced will be central to understanding the relationship between inflammation and ageing."
https://www.sciencedaily.com/releases/2020/07/200710121810.htm
Chronic inflammation in middle age may lead to thinking and memory problems later
February 13, 2019
Science Daily/American Academy of Neurology
People who have chronic inflammation in middle-age may develop problems with thinking and memory in the decades leading up to old age.
There are two kinds of inflammation. Acute inflammation happens when the body's immune response jumps into action to fight off infection or an injury. It is localized, short-term and part of a healthy immune system. Chronic inflammation is not considered healthy. It is a low-grade inflammation that lingers for months or even years throughout the body. It can be caused by autoimmune disorders like rheumatoid arthritis or multiple sclerosis, physical stress or other causes. Symptoms of chronic inflammation include joint pain or stiffness, digestive problems and fatigue.
Ways to reduce chronic inflammation include getting regular exercise, following an anti-inflammatory heart healthy diet, and getting enough sleep.
"Chronic inflammation is tough on the body, and can damage joints, internal organs, tissue and cells," said study author Keenan A. Walker, PhD, of Johns Hopkins University in Baltimore, Md. "It can also lead to heart disease, stroke and cancer. While other studies have looked at chronic inflammation and its effects on the brain in older people, our large study investigated chronic inflammation beginning in middle age and showed that it may contribute to cognitive decline in the decades leading up to old age."
As part of the Atherosclerosis Risk in Communities (ARIC) Study, researchers followed 12,336 people with an average age of 57 for approximately 20 years. Researchers took blood samples from participants at the start of the study, measuring four biomarkers of inflammation: fibrinogen, white blood cell count, von Willebrand factor, and factor VIII. They created a composite inflammation score for the four biomarkers. Three years later, researchers measured C-reactive protein, another blood biomarker of inflammation. Participants were divided into four groups based on their composite inflammation scores and C-reactive protein levels.
Participants' thinking and memory skills were tested at the beginning of the study, six to nine years later, and at the end of the study.
Researchers found the group with the highest levels of inflammation biomarkers had an 8-percent steeper decline in thinking and memory skills over the course of the study than the group with the lowest levels of inflammation biomarkers. The group with the highest C-reactive protein levels had a 12-percent steeper decline in thinking and memory skills than the group with the lowest levels. These results were derived after researchers adjusted for other factors that could affect thinking and memory skills, such as education, heart disease and high blood pressure. Further analyses revealed that inflammation-associated declines in thinking were most prominent in areas of memory, compared to other aspects of thinking such as language and executive functioning.
"Overall, the additional change in thinking and memory skills associated with chronic inflammation was modest, but it was greater than what has been seen previously associated with high blood pressure in middle age," Walker said.
"Many of the processes that can lead to a decline in thinking and memory skills are believed to begin in middle age, and it is in middle age that they may also be most responsive to intervention," said Walker. "Our results show that chronic inflammation may be an important target for intervention. However, it's also possible that chronic inflammation is not a cause and instead a marker of, or even a response to, neurodegenerative brain diseases that can lead to cognitive decline."
A limitation of the study was that participants with higher levels of chronic inflammation at the start of the study were more likely to drop out or die before the final follow-up visit, so surviving participants may not be representative of the general population.
Future studies could include more frequent assessments of thinking and memory skills. They could also examine a larger variety of inflammation markers in the blood.
https://www.sciencedaily.com/releases/2019/02/190213160535.htm
Inflammation in those with PTSD linked to changes in microRNA
- April 24, 2014
Science Daily/University of South Carolina
With a new generation of military veterans returning home from Iraq and Afghanistan, post-traumatic stress disorder (PTSD) has become a prominent concern in American medical institutions and the culture at-large. Estimates indicate that as many as 35 percent of personnel deployed to Iraq and Afghanistan suffer from PTSD. New research is shedding light on how PTSD is linked to other diseases in fundamental and surprising ways.
The rise in PTSD has implications beyond the impact of the psychiatric disorder and its immediate consequences, which include elevated suicide risk and inability to lead a normal life, that result in approximately $3 billion in lost productivity every year. Over time, these PTSD patients will continue to experience increased risks of a myriad of medical conditions like cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, musculoskeletal disorders and others, all of which share chronic inflammation as a common underlying cause.
Dr. Mitzi Nagarkatti sums up the significance of this study as follows: "We are very excited about these results. Thus far, no one had looked at the role of microRNA in the blood of PTSD patients. Thus, our finding that the alterations in these small molecules are connected to higher inflammation seen in these patients is very interesting and helps establish the connection between war trauma and microRNA changes."
In addition to the alterations in microRNA expression, the study also found that PTSD patients had higher levels of inflammation caused by certain types of immune cells called T cells. These T cells produced higher levels of inflammatory mediators called cytokines, specifically interferon-gamma and interleukin-17. This finding was especially interesting because one of the inflammation-associated microRNAs, miR-125a, which specifically targets increased production of interferon-gamma, was found to have decreased expression in the PTSD patients studied. Overall, these results suggested that trauma may cause alterations in the expression of microRNA which promote inflammation in PTSD patients.
Commenting on this, Dr. Prakash Nagarkatti said, "These studies form the foundation to further analyze the role of microRNA in PTSD. Trauma experienced during war may trigger changes in microRNA which may in turn cause various clinical disorders seen in PTSD patients. Our long-term goal is to identify whether PTSD patients express a unique signature profile of microRNA which can be used towards early detection, prevention and treatment of PTSD."
http://www.sciencedaily.com/releases/2014/04/140424102843.htm