New evidence links lifespan extension to metabolic regulation of immune system

March 25, 2019  09:31

Scientists have known for decades that caloric restriction leads to a longer lifespan. It has also been observed that chronic inflammation increases with age. But any relationship between the two had remained unexplored.

But in a new study, published today in Cell Metabolism, researchers at Joslin Diabetes Center have uncovered a new mechanism of lifespan extension that links caloric restriction with immune system regulation.

"Modulating immune activity is an important aspect of dietary restriction," says Keith Blackwell, MD, Ph.D., Associate Research Director and Senior Investigator at Joslin, and Professor of Genetics at Harvard Medical School, senior author on the paper. "And it is important for longevity regulation and, in this context, increasing lifespan."

In this study, Dr. Blackwell and his team found that caloric restriction reduces levels of innate immunity by decreasing the activity of a regulatory protein called p38, triggering a chain reaction effect ending in a reduced immune response.

Innate immunity is like the security guard of the body, keeping an eye out for any unwelcome bacteria or viruses. If the innate immune system spots something, it activates an acute immune response. We need some degree of both kinds of immunity to stay healthy, but an overactive innate immune system—which occurs more often as we age—means constant low-grade inflammation, which can lead to myriad health issues.

"[Before this study,] people looked what happens to immunity to aging in humans, but no one had ever looked in any organism at whether modulating immunity or its activities is involved in lifespan extension or can be beneficial as part of an anti-aging program," says Dr. Blackwell.

The research was conducted in the microscopic nematode worm C. elegans. The most fundamental genes and regulatory mechanisms found in these worms are typically simpler versions of those present in humans, making them a good model for studying human aging, genetics, and disease.

Dr. Blackwell and his team analyzed the levels of proteins and actions of genetic pathways during periods of caloric restriction. They were able to zero in on a particular genetic pathway that was regulated by the p38 protein. They saw that when p38 was totally inactive, caloric restriction failed and had no impact on innate immunity. When it was active, but at lower levels than normal, it triggered the genetic pathways that turned down the innate immune response to an optimal level.

Source: MedicalXpress

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