Newswise — Seeking to accelerate the pace of research into the
molecular mechanisms that govern aging, philanthropist Paul F.
Glenn, an alumnus of Harvard Law School and founder of the Glenn
Foundation for Medical Research in Santa Barbara, California, has
committed $5 million to Harvard Medical School over five years to
launch the Paul F. Glenn Laboratories for the Biological Mechanisms
of Aging.
The new resources will serve as a
magnet to attract additional support for the potential creation of a
larger Institute for Aging Research at Harvard Medical School.
“We are proud to be teaming up
with Mr. Glenn and the Glenn Foundation,” said HMS aging researcher
David Sinclair, PhD, associate professor of pathology, who will
direct the lab.
“Like us, Paul is dedicated to
finding the molecular answers to the aging process so we can
understand the mechanisms of normal aging and develop interventions
to delay its onset and decline, thereby extending the healthful
years of human life.”
To attract talented investigators
to this field and the Glenn Laboratories, a significant portion of
the resources will be used to recruit two additional faculty members
focused on aging research and to build out the labs with advanced
research technology and animal models.
Additionally, research pilot grants will be awarded by a steering
committee to investigators wanting to investigate novel areas of
molecular research addressing critical questions in the normal aging
process. These pilot grants will produce data that can be used to
attract larger government grants.
The resources will also be used to
foster collaboration by pulling together aging researchers from
around the world for an annual Paul F. Glenn Symposium on the
Molecular Biology of Aging to be held at Harvard Medical School.
“We structured this partnership in
a way that recognizes the key drivers in the scientific process, so
that the resources would be positioned to push aging research
forward more quickly and to new levels of knowledge,” said Mr.
Glenn.
“In pursuing the underlying
molecular mechanisms involved in the aging process, the Glenn
Laboratories will be supporting the broad mission of the school,”
said Nancy Andrews, MD, PhD, Dean for Basic Sciences and Graduate
Studies.
“The school and the Glenn
Laboratories research team thank Mr. Glenn and the Glenn Foundation
for their leadership in this area of science.”
Research into extending lifespan
is not new. For more than 70 years, a calorie restricted diet has
been known to increase the lifespan of mice and rats 40 percent by
preventing them from getting diseases of aging such as cancer, heart
disease, diabetes, and even cataracts.
The hypothesis is that within each
of our cells lies an evolutionarily ancient defense program that can
be activated by so-called “longevity genes” which ameliorate the
cellular damage that causes death and disease.
Activation of these genes in
genetically altered worms and flies has been shown to produce
healthier, longer lives.
Buoyed by calorie restriction animal tests, research teams in this
small field have been pursuing the molecular pathways that mimic
calorie restriction.
In the summer of 2003, Sinclair’s
team showed in a paper published in Nature that a compound found in
red wine called resveratrol could stimulate this pathway in yeast
cells.
The yeast cells lived as much as
60 percent longer, and in human cells tested in vitro, resveratrol
activated a similar pathway. It enabled 30 percent of the treated
human cells to survive gamma radiation, compared to 10 percent of
untreated cells.
In a Nature paper published in
July 2004, Sinclair’s team showed that resveratrol had a similar
impact in higher organisms: worms and flies. In worms, lifespan was
extended up to 15 percent. In flies, lifespan was extended up to 29
percent.
Another key finding with flies was
that there was no loss of fertility, which can be seen in severe
calorie restricted diets.
In a 2004 study published in the
journal Science, Sinclair's group found that a key longevity gene
called SIRT1 is switched on in rats that are subjected to calorie
restriction, which then increased the lifespan of the rat's cells.
In an interesting twist, the
research team used the blood of these long-lived rats to grow human
cells in the culture dish, and the human cells also lived longer,
suggesting that the blood might have contained a life-giving
molecule that could one day be given to people.
Although there has been much
interest in the SIRT1 gene, humans actually possess seven SIRT
genes, known as SIRT1-7. It is suspected that many, if not all, of
these genes control aspects of the aging process.
Sinclair's group is testing
whether these genes can forestall the aging process and increase the
heathspan of mice. He has also identified a master controller of the
SIRT genes, which he calls PNC1 in yeast and is called PBEF in
mammals.
Experiments to test whether mice
that overproduce PBEF live longer, as his yeast cells did, are in
progress.
Mr. Glenn’s interest in biology of
aging began as a teenager, as he observed the decline in health and
death of his grandparents.
While a senior at Princeton in
1951, he met Dr. Thomas Gardner, a research scientist at
pharmaceutical company, Hoffman-LaRoche, who explained that aging is
a complex set of biochemical processes which can be understood only
at the molecular level, and that the tools of molecular biology were
just beginning to be developed.
In 1965 Mr. Glenn founded the
Glenn Foundation for Medical Research with a mission to extend the
healthy productive human lifespan through research on the biological
mechanisms of aging.
This mission has been served
through direct sponsorship of research grants and awards programs
and through important relationships with other institutions focused
on understanding the molecular biology of aging and mechanisms that
govern the pace at which normal individuals experience physiological
decline and disease.
"As we mark our 40th anniversary,
we are very excited to establish this important relationship with
Harvard Medical School and look forward to accelerating research
into this important area" said Mark R. Collins, President of the
Glenn Foundation.
Historically financial support for
research into the biological mechanisms of aging and efforts to
extend the healthy lifespan has been spotty.
The pharmaceutical industry's
support of basic aging research is hindered due to the fact that
there are no generally accepted biomarkers for aging that would
allow the FDA to approve a drug designed to slow the aging process.
Although Congress
supplemented scarce aging research dollars by establishing the
National Institute on Aging in 1974, that money has predominately
gone to disease specific research, such as Alzheimer's disease, or
towards the behavioral aspects of aging.
"Instead of addressing individual
age related diseases, we are looking at the bigger picture. Being
able to extend the normal healthy lifespan has huge societal impact
including decreasing associated healthcare costs and increasing the
productive lifespan. By understanding the basic mechanisms of aging,
we hope to altogether avoid or mitigate the onset of age related
diseases as demonstrated by the research in caloric restriction,"
said Mr. Glenn.
"Recent discoveries of longevity
genes by Dr. Sinclair and others have persuaded me that aging
includes the phenomenon of a small group of genes controlling the
expression of a much larger group of genes, including those which
activate cellular defense mechanisms such as DNA repair. As we learn
to control expression of specific genes, we may be able to prolong
healthy cell life without a complete understanding of the
biochemical pathways involved."
In addition to funding these
important initiatives through the creation of the Paul F. Glenn
Laboratories at Harvard Medical School, it is the hope of Mr. Glenn,
the Glenn Foundation and HMS that this initiative will serve as a
catalyst for attracting new investigators and donors to support this
important field of research.
"We are very hopeful that during
this five year commitment we are able to build on the momentum we
have generated and spur the creation of an Institute at Harvard
Medical School devoted to the biology of aging, to which the Glenn
Foundation has expressed possible additional support," said Mr.
Collins.
Glenn Foundation for Medical
Research
http://www.glennfoundation.org
The Glenn Foundation for Medical Research was founded in 1965 by
Paul F. Glenn with the mission to extend the healthy, productive
years of life through research in the biological mechanisms of
aging.
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Newswise — Seeking to accelerate the pace of research into the
molecular mechanisms that govern aging, philanthropist Paul F.
Glenn, an alumnus of Harvard Law School and founder of the Glenn
Foundation for Medical Research in Santa Barbara, California, has
committed $5 million to Harvard Medical School over five years to
launch the Paul F. Glenn Laboratories for the Biological Mechanisms
of Aging.