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Monday, November 23, 2009
Recovery Act Funding Seeks to Help Understand Basic Secrets of Aging
The National Institute on Aging (NIA), part of the National Institutes of Health, today announced two major awards to advance exciting areas of basic research on aging. Grants for studies to determine the potential healthy aging effects of rapamycin, a compound involved in regulating cell growth, and to understand the causes of protein misfolding — when a protein is either not formed correctly or damaged afterwards — that lead to age-related disease are made possible through American Recovery and Reinvestment Act funding. These grants are part of the $5 billion that President Obama announced Sept. 30 on the National Institutes of Health campus.
"This is a remarkable time in aging research. Our knowledge about the basic biology of aging has grown rapidly in recent years, and the studies supported with Recovery Act funds provide a wonderful opportunity to build on what we know in some key areas," said NIA Director Richard J. Hodes, M.D. "These studies, at the cellular level, will increase our understanding of some of the basic biological processes that occur with passage of time."
Study in Mice to Determine Possible Healthy Effects of Rapamycin
NIA has awarded $5.2 million over the next two years to the University of Texas Health Science Center in San Antonio to determine the effects of rapamycin on the health of mice.
"In a recent study, a team of researchers reported that rapamycin extended the median and maximal lifespan of mice, when the drug was fed to the mice beginning in middle age. With Recovery Act funding, we can more quickly follow up on these exciting and provocative findings," said Felipe Sierra, Ph.D., director of NIA's Division of Aging Biology.
Rapamycin — an inhibitor of the mTOR pathway that helps to regulate cell growth and proliferation and that is used to help suppress the immune system in people undergoing organ transplant — is one of many compounds being studied for effects that might be similar to those of calorie restriction. Calorie restriction, very low calorie but nutritious diets that have been tested in laboratory animals and on a limited basis in humans, has been found to have variety of positive effects on health and longevity. Despite these findings, calorie restriction may not be practical or safe for most people.
The study, led by Arlan Richardson, Ph.D., will seek answers to three questions:
- How does rapamycin affect models of age-related human diseases in mice?
- How does rapamycin affect normal physiology?
- By what mechanisms does rapamycin work?
"Under normal circumstances, it took over 10 years of research to demonstrate that caloric restriction retarded age-related diseases and increased healthspan. However, Recovery Act funding will allow us to determine in two years if rapamycin can retard or reduce age-related diseases and improve quality of life in mice," said Richardson.
The team will test rapamycin's effects on multiple models of Alzheimer's disease, atherosclerosis, cardiovascular disease, Parkinson's disease, kidney disease and cancer. In addition, investigators will look at rapamycin's effects on the physiology and behavior of healthy mice, focusing special attention on the response to infection, metabolism, movement and cardiac function.
Study to Develop New Technologies to Monitor Protein Folding
NIA has awarded $1 million to Northwestern University in Evanston, Ill., and the Salk Institute in La Jolla, Calif., and $1 million to The Scripps Research Institute in La Jolla, to develop new technologies — biosensors — that will monitor aging and age-related disease by focusing on protein folding.
The proper folding of proteins in cells, or proteostasis, is important for health. Like a three-dimensional puzzle, sections of a protein naturally fold into shapes and then arrange themselves to align to each other to produce the final active protein. A protein's function in the body depends on these folding patterns. If a protein is formed incorrectly or becomes damaged and then misfolds, it disrupts the pattern. As a consequence, the protein does not perform its normal function or cannot be properly disposed of by cellular machinery. These problems and consequences on cellular proteostasis may lead to disease.
"Scientists already know that proper protein folding may be affected by age. Protein misfolding inhibits the body's ability to respond to environmental and/or physiological stresses and cues and could lead to age-related diseases like Alzheimer's or Parkinson's. This Recovery Act funding provides an opportunity to better understand the role of proteostasis and the aging environment in which protein misfolding occurs," said NIA's Sierra.
The Recovery Act funding will also support the development of the Proteostasis Aging Sensor Consortium (PASC) comprised of five investigators, representing leaders in the fields of protein folding, human cell biology and aging. The highly complementary skill sets of these investigators will create synergy to implement these new technologies within the time frame of the Recovery Act funding.
The researchers from Northwestern University led by Richard Morimoto, Ph.D., and from the Salk Institute led by Andrew Dillin, Ph.D., will develop new tools to detect protein misfolding first in a worm model and then in mammalian tissue culture cells. Researchers from The Scripps Research Institute led by William Balch, Ph.D., Jeffery Kelly, Ph.D., and Rockland Wiseman Ph.D., will use some of the tools developed by the Northwestern and Salk teams as well as their own to test protein misfolding in different compartments of mammalian cells in culture and in mice. The five investigators established the PASC to coordinate collaboration in the design, test and use of all the tools designed to follow protein folding and misfolding in cells.
"Aging is highly complex, involving multiple and variable metabolic and biochemical parameters. These studies could lead to first-in-class biosensors that would detect key features of the aging environment and its response to stress and disease," said Richard Morimoto, Ph.D., principal investigator and professor of biochemistry, molecular biology and cell biology at Northwestern University. "Ultimately, biosensors aim to enable researchers to monitor disease progression and the response to therapeutic intervention in real time."
The NIA leads the federal effort supporting and conducting research on aging and the medical, social and behavioral issues of older people. For more information on research and aging, go to www.nia.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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