Naked mole rats may hold clues to successful aging

Naked mole rats resemble pink, wrinkly, saber-toothed sausages and would never win a beauty contest, even among other rodents.

But these natives of East Africa are the champs for longevity among rodents, living nine times longer than similar-sized mice. Not only do they have an extraordinarily long lifespan, but they maintain good health for most of it and show remarkable resistance to cancer.

Researchers at The University of Texas Health Science Center at San Antonio are studying mechanisms that enable the prolonged good health and slowed aging of naked mole rats in their large colony at the university's Barshop Institute for Longevity and Aging Studies. In the March 3 print edition of Proceedings of the National Academy of Sciences, the scientists report on another unusual feature of the animals - tissues of the naked mole rat are remarkably efficient at discarding damaged proteins and thereby maintaining stable, high-quality proteins.

"Naked mole rats don't show the usual deterioration of aging, such as menopause or decline in brain function," said paper co-author Rochelle Buffenstein, Ph.D., professor of physiology at the Barshop Institute and one of the world's leading experts on aging in naked mole rats. "They demonstrate a healthy longevity that all of us would like to emulate."

In most organisms, proteins are tagged for destruction, and a garbage disposer, called the "proteasome," picks up the damaged ones and recycles their amino acids for new protein formation. The research team found very low levels of tagged proteins for destruction in naked mole rats, indicating they have better-quality protein as well as more efficient removal of damaged proteins. The result is the damaged ones do not accumulate and cause havoc in cells. "We now believe the level of protein damage in the naked mole rats is not as critical as their ability to dispose of the insults efficiently," said the paper's senior author, Asish Chaudhuri, Ph.D., assistant professor of biochemistry at the Barshop Institute.

The scientists compared naked mole rat tissues to those of laboratory mice. The specimens from naked mole rats were far superior at handling stress-induced damaged proteins.

"It's been suggested that damaged proteins clump into globs that are toxic to cells, and these globs are believed to be very important in age-related neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's and Lou Gehrig's diseases," said the lead author, Viviana Perez, Ph.D., postdoctoral fellow at the Barshop Institute. "Finding a way to emulate the naked mole rats' ability to effectively dispense of damaged proteins might lead to drugs to treat these diseases one day."

The researchers' next step is to determine whether tissues of other animals that are long-lived, such as certain birds, also possess a similar ability to efficiently dispose of damaged proteins. Eventually, tissues from primates and even humans could be studied to test the universality of "this protein-disposing theory," Dr. Chaudhuri said.

"Understanding how naked mole rats better control protein quality may yield important insights for how we as humans can sustain good health," Dr. Buffenstein said. "We might also learn something about treating age-associated degenerative diseases. The naked mole rats clearly hold the clues to successful aging."

More information about the paper:

* Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole rat; Proceedings of the National Academy of Sciences , March 3, 2009; Viviana Perez1,4, Rochelle Buffenstein1,2,4,7, Venkata Masamsetti4, Shanique Leonard4, Adam Salmon4, James Mele2,4, Blazej Andziak7, Ting Yang7, Yael Edrey7, Bertrand Friguet3, Walter Ward2,4, Arlan Richardson1,4,5 and Asish Chaudhuri4,5,6

Departments of Cellular & Structural Biology1, Biochemistry6 and Physiology2, Barshop Institute for Longevity and Aging Studies4, The University of Texas Health Science Center at San Antonio; Geriatric Research, Education & Clinical Center5, South Texas Veterans Health Care System, San Antonio; Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement3, University of Paris; and Department of Biology7, Graduate School of the City University of New York.

About the Health Science Center:

The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $668 million, the Health Science Center is the chief catalyst for the $16.3 billion biosciences and health care sector in San Antonio's economy. The Health Science Center has had an estimated $36 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 25,600 graduates (physicians, dentists, nurses, scientists and other health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, dentistry and many other fields. For more information, visit www.uthscsa.edu.