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"Now that we've identified this mechanism in the Nlrp3 sensor, we might be able to manipulate this immune sensor to delay, or reduce inflammation," says Vishwa Deep Dixit. "This could lead to the possibility of prolonging healthspan, potentially leading to an old age relatively free of disease or disability." (Credit: "senior woman swimming" via Shutterstock)

aging

Inflammation alone can cut ‘healthspan’

Scientists have spotted a common trigger of inflammation-driven loss of function that causes insulin-resistance, bone loss, frailty, and cognitive decline in aging.

Even in the absence of a disease, inflammation can lead to serious loss of function throughout the body, reducing “healthspan”—that portion of our lives spent relatively free of serious illness and disability—according to a new study.

As the elderly population increases, clinicians are seeing a spike in age-related diseases such as arthritis, gout, Alzheimer’s, and diabetes, but scientists did not fully understand the role of inflammation. What is commonly known is that as we age, our cells change, leading the immune system to produce chronic, low-level inflammation throughout the body.

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Aging is also a major risk factor for multiple chronic diseases, but according to the researchers, biomedical enterprise spends billions of dollars to tackle each age-dependent disease separately.

“This is the first study to show that inflammation is causally linked to functional decline in aging,” says lead author Vishwa Deep Dixit, professor of comparative medicine and immunobiology at Yale School of Medicine. “There are multiple cellular triggers of inflammation throughout the body, but we’ve pinpointed Nlrp3 as the specific sensor that activates inflammation with age.”

“If aging is indeed a common factor for multiple diseases, the unanswered question is, can we identify the triggers of aging that cause low-level inflammation so that ‘switching off’ the trigger can slow the onset of multiple chronic diseases that are age-dependent at their onset,” Dixit adds.

“Since aging affects us all, if this goal can be achieved, it is likely to significantly improve the healthspan and may also lower healthcare costs as the aging population increases in the US.”

Inflammasome tests

As reported in Cell Metabolism, Dixit and his colleagues investigated the normal aging process of mice that were free of diseases, and fed a normal diet. The research team found that immune sensor Nlrp3 inflammasome is activated in response to aging.

They then tested mice to determine if reducing the activity of Nlrp3 inflammasome lowers inflammation, and aging-associated decline in function. Results showed that animals with lower Nlrp3 activation were protected from many age-related disorders such as dementia, bone loss, glucose intolerance, cataracts, and thymus degeneration. Functionally, the mice also performed better, were less frail, and ran for longer durations.

The researchers also tested another immune sensor called caspase11, which is activated in response to certain infections, and found that it was not linked to the age-related inflammation process.

Better old age

“Now that we’ve identified this mechanism in the Nlrp3 sensor, we might be able to manipulate this immune sensor to delay, or reduce inflammation,” Dixit says. “This could lead to the possibility of prolonging healthspan, potentially leading to an old age relatively free of disease or disability.”

Dixit says additional studies are needed to explore whether the Nlrp3 mechanism can be safely manipulated without impairing the immune system. He points out that although there are several anti-inflammatory drugs available, none seem to be effective in expanding the healthspan.

“One of our long-term goals is to develop therapies or specific diets that could dampen the excessive inflammation process as a means to prevent chronic diseases,” he says.

The National Institutes of Health; The Genomics and Core CBB Core facilities supported by Pennington Center of Biomedical Research Excellence; and Nutrition and Obesity Research Center supported the research.

Source: Yale University

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