Nearly one quarter of the U.S. population will be over age 65 by 2040, according to the U.S. Census Bureau, and those reaching age 65 have an average life expectancy of an additional 19.2 years. Ensuring the healthy and productive lives of that very large group is becoming an urgent priority, says Janko Nikolich-Žugich, MD, PhD, co-director of the University of Arizona Center on Aging.
“Research has shown that consuming fewer calories, while maintaining sufficient nutrients, extends lifespan and there are ongoing clinical studies in humans. However, aging also is associated with increased susceptibility to diseases,” Dr. Nikolich-Žugich notes.
Now, researchers at the UA College of Medicine – Tucsonare beginning to study lifespan extension and immune function, thanks to a two-year $403,751 grant from the National Institute on Aging of the National Institutes of Health.
“Remarkable extension of lifespan has been achieved in organisms by lowering calorie intake or tricking cells into thinking that there is not enough food. These manipulations are being considered for potentially increasing lifespan in humans,” says Dr. Nikolich-Žugich, principal investigator of the study, Longevity Extension and Immune Function in Aging. “It is critical to understand the effects of these interventions upon physiological function of older organisms, as any increase in longevity must be accompanied by improved quality of life.”
Rapamycin (Rapa), a drug used to keep the body from rejecting organ and bone marrow transplants, blocks an enzyme that controls cellular division. Rapa has been shown to extend lifespan in mice, however, the effects of chronic low-dose Rapa-mediated treatment on resistance to infection remain unknown.
“Our study will test whether life-extending dietary interventions may improve or impair survival from, and immunity to, infection, allowing us to evaluate whether manipulations of nutrient pathways may be safe and desirable to achieve optimal healthy longevity,” says Dr. Nikolich-Žugich, who also is chairman of the UA Department of Immunobiologyand the Elizabeth Bowman Professor in Medical Research at the UA College of Medicine – Tucson and a member of the UA BIO5 Institute.
“While calorie restriction appears to improve immune function and homeostasis in old animals, the few infectious challenge experiments suggest increased susceptibility to infection. Our exploratory proposal aims to test the hypothesis that calorie restriction and drugs that trick the cells into thinking that there is not enough food, such as Rapa, could be deleterious for protective immunity, because they may curtail full development of immune responses,” notes Dr. Nikolich-Žugich.
UA researchers will look for protective T cell (a type of white blood cell) and antibody responses to West Nile Virus (a virus transmitted by arthropods, such as mosquitoes or ticks) or listeria (a food-borne bacterium), which cause high mortality in older adults. Researchers will measure the efficacy and the type of the immune response. “We aim to dissect possible defects and discover whether we may use Rapa as is or whether we may need to seek for similar compounds with beneficial effects in healthy aging across different tissues,” says Dr. Nikolich-Žugich.
A paper related to the study has been published in the July 15 issue of The Journal of Immunology, a publication of the American Association of Immunologists, Inc. Lead author on the paper, “Immune Memory Boosting Dose of Rapamycin Impairs Macrophage Vesicle Acidification and Curtails Glycolysis in Effector CD8 Cells, Impairing Defense against Acute Infections,” is Emily L. Goldberg, PhD, postdoctoral research associate, Department of Immunobiology, and member of the UA Center on Aging. In addition, UA researchers who contributed to the paper include UA Center on Aging members: Megan J. Smithey, PhD, research assistant professor, Department of Immunobiology; Lydia K. Lutes, undergraduate laboratory assistant, Department of Immunobiology; and undergraduate student in the Department of Molecular and Cellular Biology, UA College of Science; Jennifer L. Uhrlaub, research associate, Department of Immunobiology; and Dr. Nikolich-Žugich.
This research is supported by the National Institute on Aging of the National Institutes of Health under Award No. R21AG045734. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About the University of Arizona Center on Aging
The mission of the University of Arizona Center on Aging (ACOA) at the UA College of Medicine – Tucson is to promote long and healthy lives of older adults through coordinated programs in research, education, outreach and patient care. Established in 1980 as one of a network of Long Term Care Gerontology Centers authorized by the Older Americans Act, the ACOA was approved by the Arizona Board of Regents as a Center of Excellence at the Arizona Health Sciences Center in 1991. For more information, please visit the center’s website: www.aging.arizona.edu
About the UA Department of Immunobiology
The Department of Immunobiology, one of the five basic science departments at the University of Arizona College of Medicine – Tucson, conducts cutting-edge research in the development, function and regulation of the immune system in health and disease. Areas of study include the biology of microorganisms and their interaction with the immune system over the lifespan of the individual. Department faculty seek to improve and regulate the function of the immune system to reduce and prevent illness and death from infectious and autoimmune diseases and cancer. The department educates medical and other health sciences students, physicians and scientists in all areas of immunobiology and microbiology. For more information, please visit the website: http://immunobiology.arizona.edu
Thursday, July 24, 2014 - 14:02