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Proteasome Protection May Be Clue to Unusual Longevity of the Naked Mole Rat

Scientists at the Barshop Institute for Longevity and Aging Studies, part of the School of Medicine at the University of Texas (UT) Health Science Center at San Antonio, have found another secret of longevity in the tissues of the longest-lived rodent, the naked mole rat. They reported that a factor in the cells of naked mole rats protects and alters the activity of the proteasome, a garbage disposer for damaged and obsolete proteins. The factor also protects proteasome function in human, mouse, and yeast cells when challenged with various proteasome poisons, studies showed. These proteasomes usually rapidly stop functioning when poisoned, leading to the accumulation of damaged proteins that further impair cell function, contributing to the vicious cycle that leads to cell death. "I think this factor is part of an overall process or mechanism by which naked mole rats maintain their protein quality," the study’s first author Karl Rodriguez, Ph.D., said. This finding was reported online on July 10, 2014 in the journal Biochimica et Biophysica Acta (BBA): Molecular Basis of Disease. Generally, as an organism ages, not only are there more damaged proteins in need of disposal, but the proteasome itself becomes damaged and less efficient in clearing out the damaged proteins. As a result, protein quality declines and this contributes to the functional declines seen during aging. Enhancement of protein quality, meanwhile, leads to longer life in yeast, worms, fruit flies, and naked mole rats, Dr. Rodriguez said. Dr. Rodriguez, a San Antonio native who completed both his master's and doctoral degrees at the Health Science Center, is a postdoctoral fellow in the laboratory of Rochelle Buffenstein, Ph.D., professor of physiology at the Barshop Institute. For this study, the Buffenstein lab also collaborated with Pawel Osmulski, Ph.D., assistant professor of molecular medicine; Susan Weintraub, Ph.D., professor of biochemistry; and Maria Gaczynska, Ph.D., associate professor of molecular medicine. Naked mole rats, which burrow through underground tunnels in their native East Africa, are nearly hairless rodents. They live as long as 32 years. Naked mole rats maintain cancer-free good health and reproductive potential well into their third decade of life. Image is courtesy of the UT Health Science Center at San Antonio. [Press release] [BBA: Molecular Basis of Disease abstract]