UCSF 'fountain of youth' pill could restore aging immune system

December 13, 2010

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 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 researchers said. Data will appear in the January issue of the journal Clinical Immunology, and can be found online at www.elsevier.com/locate/yclim.

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.

"No one's really talking about longevity and lifespan now, but about 'health span,'" said Goetzl, director of UCSF Allergy and Immunology Research, which focuses on developing new diagnostics and treatments for allergic and immunological diseases.

"If, at age 50, your cytokine levels are the same as they were at 25, you'll probably stay healthy as you age," he said. "But if they're heading downhill, we need to do something about it. If you could take a low-dosage pill with no side effects, wouldn't you do it?"

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, 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 IL-17, which is linked to inflammation. 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.

"We now had a profile - in humans - that we could take to test tubes to say, 'Does this drug have a desirable effect?'" Goetzl said. "Our job was to find a therapy that not only works, but does so at a dose range with no side effects."

The team focused on three classes of drugs, among them the one that includes lenalidomide - a derivative of thalidomide - which is undergoing a renaissance, Goetzl said.

First introduced in the late 1950s as a sedative, thalidomide was never approved in the United States, but was withdrawn from the world market in 1961 after causing severe birth defects in infants whose mothers took the drug to reduce nausea during pregnancy.

In recent years, however, lenalidomide has been found to be an effective co-therapy for some cancers, particularly multiple myeloma and kidney tumors, as well as leprosy, at doses of 5 mg to 20 mg per day. Those cancers are tied to a drop in IL-2, the main cytokine that Goetzl's team had linked to declines in aging immune systems.

In this study, the team tested the drug in healthy seniors, each of whom were matched in race, gender and national origin to a healthy young adult participant. They found that extremely low levels of lenalidomide - 0.1 μM - optimally stimulated IL-2 production in the young people (21-40 years) roughly sevenfold, but stimulated IL-2 production in patients over age 65 by 120-fold, restoring them to youthful levels for up to five days. At that dosage, the drug also increased IFN-gamma up to six fold in the elderly patients, without suppressing IL-17 generation.

The researchers also found that lenalidomide had many other beneficial effects on the elderly participants' T cells, including better migration throughout the body, more efficient patrolling activity and longer survival after defending the body against an infection.

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.
-end-
The research was supported by a grant from the Kenneth Rainin Foundation and by the Intramural Research Program of the National Institute on Aging. The authors declare no conflicts of interest.

The first author on the paper is Mei-Chuan Huang, who, along with Goetzl and co-author Janice B. Schwartz, is from the UCSF departments of Microbiology-Immunology and of Medicine. Co-authors are Nigel Greig, Weiming Luo, David Tweedie, Dan Longo, Luigi Ferrucci and William B. Ershler, all from the National Institute on Aging, of the National Institutes of Health, in Baltimore.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

University of California - San Francisco

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.