[extropy-chat] philanthropist funds Harvard Aging Research

[Damien Broderick]

http://www.eurekalert.org/pub_releases/2005-03/hms-ppf031105.php

Philanthropist Paul F. Glenn launches labs for aging research at Harvard
Medical School

Five year, five million dollar commitment with goal of leveraging larger
initiative

BOSTON, MA--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.