Testing “Fountain of Youth” Pill
on Senior Citizens to Restore Aging Immune System
UCSF
study of seniors finds low levels of lenalidomide boosted key cytokines,
greatly increasing immunity
Dec.
14, 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.
Are
American senior citizens who say they're happy simply part of an era
that predisposed them to good cheer? Or do most people – whether born
and raised in boom times or busts – have it within themselves to reach
their golden years with a smile?
Vibration
therapy lacks cardiovascular benefit of exercise
for senior citizens, but it can improve muscle strength and weight loss
- See video in story on how it works
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, 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.
“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 senior citizens, 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.
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.
Keep up with the latest news for senior citizens, baby
boomers
Dec.
14, 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.
