December 28, 2014

Antiaging Rapamycin used to boost immune response in humans

Mannick and her colleagues decided to investigate whether a rapamycin-like drug could reverse the natural decline that elderly people experience in their ability to fight off infections.

In the clinical trial, more than 200 people age 65 and older randomly received either the experimental drug or a placebo for several weeks, followed by a dose of flu vaccine.

Flu is particularly hard on seniors, with people 65 and older accounting for nine out of 10 influenza-related deaths in the United States, according to background information provided by the researchers.

Those who received the experimental version of rapamycin developed about 20 percent more antibodies in response to the flu vaccine, researchers found. Even low doses of the medication produced an improved immune response.

Science Translational Medicine - mTOR inhibition improves immune function in the elderly



The researchers also found that the group given the drug generally had fewer white blood cells associated with age-related immune decline.

Mannick called this study the "first baby step," and was reluctant to say whether it could lead to immune-boosting medications for the elderly.

"It's very important to point out that the risk/benefit of MTOR inhibitors should be established in clinical trials before anybody thinks this could be used to treat aging-related conditions," she said.

Barzilai was more enthusiastic. Research such as this could revolutionize the way age-related illnesses are treated, he said.

"Aging is the major risk factor for the killers we're afraid of," he said, noting that people's risk for heart disease, cancer and other deadly illnesses increases as they grow older. "If the aging is the major risk, the way to extend people's lives and improve their health is to delay aging."

Rapamycin belongs to a group of drugs called mTOR inhibitors, which have been shown in previous studies to work as anti-aging agents. As people age, mTOR genetic pathways seem to have a negative effect on them, though they support healthy growth in children (this goes for all mammals). So using rapamycin to inhibit the mTOR genetic pathway could, in theory, delay aging. In a 2013 study, for example, researchers discovered that rapamycin worked to increase both “mean and maximum life spans” in mice.

However, this is the first time that researchers are studying rapamycin’s effect in humans. While more research is needed to better gage whether rapamycin can extend human lifespan like it does in mice, the study shows that it boosts older people’s immune systems, particularly against the flu: which can be especially dangerous to elderly.

Abstract - TOR inhibition improves immune function in the elderly

Inhibition of the mammalian target of rapamycin (mTOR) pathway extends life span in all species studied to date, and in mice delays the onset of age-related diseases and comorbidities. However, it is unknown if mTOR inhibition affects aging or its consequences in humans. To begin to assess the effects of mTOR inhibition on human aging-related conditions, we evaluated whether the mTOR inhibitor RAD001 ameliorated immunosenescence (the decline in immune function during aging) in elderly volunteers, as assessed by their response to influenza vaccination. RAD001 enhanced the response to the influenza vaccine by about 20% at doses that were relatively well tolerated. RAD001 also reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. These results raise the possibility that mTOR inhibition may have beneficial effects on immunosenescence in the elderly.

SOURCES - Medical Daily, Science Translational Medicine