Factor in naked mole rat’s cells enhances protein integrity

Barshop Institute finding is clue of how African rodent defies aging

SAN ANTONIO (Aug. 29, 2014) — Scientists at the Barshop Institute for Longevity and Aging Studies, part of the School of Medicine at the 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, 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,” study first author Karl Rodriguez, Ph.D., said.

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.

This finding is in the journal BBA: Molecular Basis of Disease.


Biochim Biophys Acta 2014 Jul 10. Epub 2014 Jul 10. http://www.sciencedirect.com/science/article/pii/S0925443914002166

A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition

Karl A. Rodriguez a,b, Pawel A. Osmulski a,c, Anson Pierce d, Susan T. Weintraub f,g, Maria Gaczynska a,c, Rochelle Buffenstein a,b,e

a Sam and Ann Barshop Institute for Aging and Longevity Studies, The University of Texas Health Science Center at San Antonio
b Department of Physiology, The University of Texas Health Science Center at San Antonio
c Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio
d Mitchell Center for Neurodegenerative Diseases, Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston
e Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio
f Department of Biochemistry, The University of Texas Health Science Center at San Antonio
g Mass Spectrometry Laboratory, The University of Texas Health Science Center at San Antonio


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