An Overactive Immune System Protects Against Infection at the Cost of More Rapid Aging

Greater immune activity implies greater inflammation, which has a negative impact on tissue function if maintained over time. In aging, a great deal of damage is done by the chronic inflammation of an overactive immune system. Researchers here provide evidence to indicate that the evolved state of immunity is a balancing act between a faster pace of aging on the one hand, resulting from an immune system that is more active, and vulnerability to infection on the other, resulting from an immune system that is less active.

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?

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.

PUF60 works as a 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.



I was glad to see this study mentioned as this topic has long been a question in my mind. Rhetorically, are people that rarely get sick and/or heal quickly tend to live longer because they have a "strong" immune system or shorter because the immune system is "overactive"? This study suggests "overactive" immune system can be a factor. My understanding of case reports from centenarians is counter-point and that many centenarians say they rarely got sick their entire life. Balance is likely in play, but what and where is balance?

Posted by: Dave at July 19th, 2020 3:37 PM
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