Hochbegabungspresse
Substance makes mice live longer, but hardly slows down
the aging process
Bonn, Germany, July 25, 2013 - The drug rapamycin is
known to increase lifespan in mice. Whether rapamycin slows down aging,
however, remains unclear. A team of researchers from the German Center for
Neurodegenerative Diseases (DZNE) and the Helmholtz Zentrum München has now
found that rapamycin extends lifespan - but its impact on aging itself is
limited. The life-extending effect seems to be related to rapamycin's
suppression of tumors, which represent the main causes of death in these mouse
strains. The findings are reported in the current issue of the "Journal of
Clinical Investigation" (published online on July 25, 2013).
The body's repair mechanisms begin to fail with increasing
age. As a result, signs of wear and tear appear and the risk for many diseases,
including Alzheimer's disease, diabetes, cardiovascular disorders and cancer,
increases. "Current efforts to develop therapies against age-related
diseases target these disorders one by one," says Dr. Dan Ehninger,
research group leader at the DZNE site in Bonn. "Influencing the aging
process itself may be an alternative approach with the potential to yield
broadly effective therapeutics against age-related diseases."
In this context, the substance rapamycin is noteworthy.
Rapamycin is used in recipients of organ transplants, as it keeps the immune
system in check and can consequently prevent rejection of the foreign tissue.
In 2009, US scientists discovered another effect: Mice treated with rapamycin
lived longer than their untreated counterparts. "Rapamycin was the first
drug shown to extend maximal lifespan in a mammalian species. This study has
created quite a stir," says Ehninger.
For Ehninger and his team, this finding motivated further
studies: "We wanted to address if rapamycin slows down aging in mice or,
alternatively, if it has an isolated effect on lifespan - without broadly
modulating aging."
Not a youth elixir
Together with scientists from the Helmholtz Zentrum München
and other colleagues, Ehninger's group investigated if rapamycin influences
aging in mice. The results are sobering: "Our results indicate that
rapamycin extends lifespan, but it has only limited effects on the aging
process itself," is Ehninger's summary of the findings. "Most aging
traits were not affected by rapamycin treatment. Although we did observe
positive effects on some aging traits, such as memory impairments and reduced
red blood cell counts, our studies showed that similar drug effects are also
seen in young mice, indicating that rapamycin did not influence these measures
by slowing aging, but rather via other, aging-independent, mechanisms."
The researchers believe that such aging-independent drug
effects also underlie rapamycin's effect on lifespan. "We assume that the
lifespan of mice is extended because rapamycin inhibits tumor formation. This
is a well-known rapamycin effect, which we were able to confirm. Cancer is the
leading cause of death in the relevant mouse strains" says the specialist
in molecular medicine. "Rapamycin, therefore, seems to have isolated
effects on specific life-limiting pathology, but lacks broad effects on aging
in mice."
A comprehensive assessment of aging
The research team assessed more than 150 traits, which
typically change during the course of aging. These analyses included an
assessment of vision, reflexes, cardiovascular function, learning and behavior,
immune functions and the integrity of the arterial wall, to just name a few.
"Aging is a complex process, which cannot be captured by assessing a
single parameter. This is why we analysed a large number of structural and
functional signs of aging," explains Ehninger. "The present study is
one of the most comprehensive assessments of a putative anti-aging
intervention."
The analysis comprised three different age cohorts, in
which rapamycin treatment was either initiated in young adulthood, in midlife
or late in life. "At the time, the US study showed that rapamycin extends
lifespan irrespective of whether the treatment is given to young or aged
animals," says the Bonn-based researcher. "We, therefore, chose a
study design, in the context of which we also investigated rapamycin's effects
on different age groups. This enabled us to examine whether the possible
effects of rapamycin depend on the age at which treatment started."
The animals were genetically identical twin mice. All of
the animals received rapamycin regularly over a period of approximately one
year. For each age cohort there was also a control group, which did not take
the substance.
Need for comprehensive analyses
"Generally speaking, our studies show that a number
of different parameters have to be considered when assessing the efficacy of
possible anti-aging interventions. The interpretation of the data depends
heavily on the overall picture of findings. Lifespan measures alone are not a
reliable indicator of anti-aging effects," emphasises Ehninger. "This
makes the search for anti-aging medicines tedious, but it is also very
promising, because such substances could open up new possibilities for medicine.
However, this is still some way off."
Original publication
"Rapamycin extends murine lifespan but has limited
effects on aging ", Frauke Neff, Diana Flores-Dominguez etc., Journal of
Clinical Investigation (published online on July 25, 2013), http://dx.doi.org/10.1172/JCI67674
The German Center for Neurodegenerative Diseases (DZNE)
investigates the causes of diseases of the nervous system and develops
strategies for prevention, treatment and care. It is an institution of the
Helmholtz Association of German Research Centres with sites in Berlin, Bonn,
Dresden, Göttingen, Magdeburg, Munich, Rostock/Greifswald, Tübingen and Witten.
The DZNE cooperates closely with universities, their clinics and other research
facilities. Website: www.dzne.de/en /
Twitter: twitter.com/DZNE_en
Contact
Dr. Dan Ehninger
Research Group Leader
DZNE, Bonn
Tel.: +49 228 43302-683
E-Mail: dan.ehninger@dzne.de
Dr. Dirk Förger
Head of Press and Public Relations
DZNE, Bonn
Tel.: +49 228/43302-260
E-Mail: presse@dzne.de