Controlling Triggers of Age-Related Inflammation Could Extend 'Healthspan'

From ScienceDaily website (see original article)

Oct. 21, 2013 — Inflammation is the common denominator of many chronic age-related diseases such as arthritis, gout, Alzheimer's, and diabetes. But according to a Yale School of Medicine study, 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.

Published as the cover article in the October issue of Cell Metabolism, the study found that immune sensor Nlrp3 inflammasome is a common trigger of this inflammation-driven loss of function that manifests itself in insulin-resistance, bone loss, frailty, and cognitive decline in aging.

As the elderly population increases, clinicians are seeing a spike in age-related diseases, 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.
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," said 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 added. "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 U.S."

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.

"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 said.
"This could lead to the possibility of prolonging healthspan, potentially leading to an old age relatively free of disease or disability."

Dixit said 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 said.

Low Testosterone Levels May Herald Rheumatoid Arthritis in Men

From Science Daily website (see original article)

Apr. 3, 2013 — Low testosterone levels may herald the subsequent development of rheumatoid arthritis in men, suggests research published online in the Annals of the Rheumatic Diseases.

Sex hormones are thought to play a part in the development of rheumatoid arthritis, and both men and women with the condition tend to have lower levels of testosterone in their blood than healthy people.
But it is not clear whether this is a contributory factor or a consequence of the disease.

The researchers based their findings on participants of the Swedish Malmo Preventive Medicine Program (MPMP), which began in 1974 and tracked the health of more than 33,000 people born between 1921 and 1949.

As part of their inclusion in the Program, participants were subjected to a battery of tests, completed a questionnaire on health and lifestyle factors, and left blood samples after an overnight fast.

The authors identified all those MPMP participants who were subsequently diagnosed with rheumatoid arthritis up to December 2004 by cross checking national and regional registers.

Stored blood samples were available for 104 of the men who subsequently developed rheumatoid arthritis, and for 174 men of the same age who did not develop the disease.

The average period of time that elapsed between donating the blood sample and a diagnosis of rheumatoid arthritis was just under 13 years, but ranged from one to 28.

Rheumatoid factor status was known at diagnosis for 83 of the men, almost three out of four (73%) of whom tested positive for it; the rest tested negative. Rheumatoid factor is an antibody that indicates disease severity and is used to categorise the condition.

After taking account of smoking and body mass index, both of which can affect the risk of rheumatoid arthritis, men with lower levels of testosterone in their blood samples were more likely to develop the disease.

This was statistically significant for those who tested negative for rheumatoid factor when they were diagnosed.

These men also had significantly higher levels of follicle stimulating hormone -- a chemical that is involved in sexual maturity and reproduction -- before they were diagnosed with rheumatoid arthritis.
This is likely to be secondary to reduced testosterone production, say the authors.

The findings prompt them to suggest that hormonal changes precede the onset of rheumatoid arthritis and could influence disease severity.

They point to other studies, which indicate that testosterone may dampen down the immune system, so quelling inflammation. Rheumatoid arthritis is also more likely to go into remission in its early stages in men, they say.