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December 13, 2010

Pill for restoring the aging immune system to a more youthful state

UCSF researchers have identified an existing medication that restores key elements of the immune system that, when out of balance, lead to a steady decline in immunity and health as people age. The team plans to begin larger-scale clinical trials in 2011 to test the drug’s effectiveness and hopes for broader availability within a few years.

The team found that extremely low doses of the drug lenalidomide can stimulate the body’s immune-cell protein factories, which decrease production during aging, and rebalance the levels of several key cytokines – immune proteins that either attack viruses and bacteria or cause inflammation that leads to an overall decline in health.

The initial study, which was designed to define the dose range of such a therapy in a group of 13 patients, could lead to a daily pill to boost immunity in the elderly



The identification of a drug to reverse the immunological decline in aging, known as immunosenescence, is the culmination of years of research by Edward J. Goetzl, MD, at UCSF and the National Institute on Aging, into how cytokine levels change as people age, how that varies by gender, and which changes dictate whether someone will be healthy into their 90s or begin a downward cycle of decline starting in middle age.

In 2009, Goetzl had studied a group of 50 elderly adults through the National Institute on Aging, examining their levels of key cytokines – Interleukin (IL)-2, IFN-gamma and IL-17 – and discovered that truly healthy 70-80 year old women had the same levels of those as did healthy 20 year olds.

However, some elderly men and frail women who showed increased levels of inflammatory diseases and weakened defenses against infections tended to have lower levels of the first two cytokines, which are protective, and higher levels of inflammatory cytokines. That imbalance, the researchers found, began in late middle age.

They then set out to find a drug that could raise IL-2 and IFN-gamma and either have no effect on IL-17 or lower it.



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