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A Pioneering Program Funded By Life Extension® To Protect Against Cancers and Slow Aging

May 2015

By Ben Best

The Life Extension Foundation® supports dozens of scientists seeking to meaningfully extend the healthy human life span through their unique research initiatives.

I believe that Vera Gorbunova, PhD, and Andrei Seluanov, PhD, are two of the most productive anti-aging researchers receiving grants from the Life Extension Foundation®.

Drs. Gorbunova and Seluanov are a husband-and-wife team at the University of Rochester in Rochester, New York. The couple have two children and often co-author papers published in peer-reviewed journals. Both scientists are devoted to finding means to reduce aging and cancer so as to extend human life span.1

Dr. Vera Gorbunova

Dr. Vera Gorbunova
Dr. Vera Gorbunova

Dr. Gorbunova teaches a popular course on the biological causes of aging at the University of Rochester. She was one of the organizers of the 2014 Genetics of Aging Conference held at Cold Spring Harbor Laboratory. As described in the November 2013 issue of Life Extension® magazine, Dr. Gorbunova discovered that the sirtuin SIRT6 could more than triple the repair of DNA damage.2 Increased levels of SIRT6 has been shown to extend the life span of male mice 10 to 15%.3 Because DNA damage can lead to both aging and cancer, Dr. Gorbunova has been looking for molecules that will stimulate SIRT6 activity. As described in the January 2014 issue of Life Extension® magazine, Dr. Gorbunova was denied government funding on the grounds that there are other mechanisms of DNA repair besides what SIRT6 stimulates. Grants from the Life Extension Foundation® have enabled Dr. Gorbunova to continue her work on SIRT6 activation of DNA repair.

Dr. Andrei Seluanov

Dr. Andrei Seluanov
Dr. Andrei Seluanov

As described in the May 2014 issue of Life Extension® magazine, Dr. Seluanov has the second-largest naked mole rat colony in the world. Although mice frequently die of cancer, cancer has never been reported in a naked mole rat.4,5 Naked mole rats live about 10 times longer than mice without evidence of aging or age-related diseases.6 As described in the January 2014 issue of Life Extension® magazine, Dr. Seluanov was denied funding from the government on the grounds that the genome of the naked mole rat had already been sequenced to discover the basis of naked mole rat cancer-resistance and longevity. Without funding from the Life Extension Foundation®, Dr. Seluanov would have been in danger of losing his naked mole rat colony. Although Gorbunova and Seluanov contributed to analysis of the naked mole rat genome,7 this information was insufficient to explain the cancer-resistance and longevity of the naked mole rat. (The lead researcher for the naked mole rat genome analysis was João Pedro de Magalhães, PhD, of the University of Liverpool, who the Life Extension Foundation® funded to sequence the genome of the longest-lived mammal, the bowhead whale, which lives over 200 years.)

Cancer Resistance And Longevity

Cancer Resistance And Longevity  

On July 18, 2013, Drs. Seluanov and Gorbunova made the cover of the prestigious journal Nature with their discovery that high molecular weight hyaluronan (hyaluronic acid) in naked mole rats protects them from cancer.8 Naked mole rat hyaluronan is 5 times larger than the hyaluronan in humans or mice. Hyaluronan is found in skin products. In other mammals, hyaluronan contributes to wound healing.9 But in the naked mole rat, the high molecular weight hyaluronan causes cancer cells to stop growing.8 A few years earlier, Dr. Seluanov had discovered that naked mole rat tissue causes cancer to stop growing,10 but he had not understood the reason.

With funding from the Life Extension Foundation®, the couple discovered that protein synthesis is 4 times more accurate in naked mole rats than in mice.11 Many neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are associated with protein misfolding, which is likely in part due to errors in protein synthesis.12 Precision synthesis of proteins by naked mole rats contributes to their cancer-resistance and longevity.

Both the hyaluronan discovery and the protein synthesis fidelity discovery caused the prestigious journal Science to name the naked mole rat “Vertebrate of the Year” for 2013.13

Early in 2014, with funding from the Life Extension Foundation®, the couple were able to report novel husbanding innovations that facilitated the survival of naked mole rat pups.14

Drs. Gorbunova and Seluanov have been studying rodents to understand differences in cancer resistance and longevity between species. The August 2014 issue of Nature Reviews: Genetics featured a review as a cover story on that subject that was primarily authored by the two scientists.15 Nature Reviews: Genetics is the foremost scientific journal (highest impact factor) on the subject of heredity and genetics. The Life Extension Foundation® was acknowledged as a funding source for the review.

Mole Rat Study

Mole Rat Study  

There are more rodents in the world than any other mammal. Roughly 40% of all mammals are rodents. The largest rodent (capybara) is over 1,000 times larger than the smallest rodent (mouse). In general, the largest animals like elephants and whales are the most long-lived. This fact is somewhat paradoxical because the many cells in large animals—and the growth required to achieve such a large body—should increase the likelihood of developing cancer. Large animals must have a special anticancer mechanism, but the nature of that mechanism is as yet not fully determined. In contrast to other animals, however, the longest-lived rodent is the naked mole rat, which is about the size of a mouse. The blind mole rat, which is the second most long-lived rodent, is also about the size of a mouse. Like the naked mole rat, the blind mole rat has never been observed to develop cancer.16 Gorbunova and Seluanov have shown that the blind mole rat eradicates cancer by a different method than the naked mole rat—by a hair-trigger inflammatory response that causes massive cell death in any area where cancer begins to appear. Although large mammals (like whales and elephants) and large rodents (like beavers and porcupines) have better DNA repair than small animals, this mechanism alone is not sufficient to explain the suppression of cancer.

The Life Extension Foundation® is grateful to be able to fund such talented and productive researchers as Dr. Vera Gorbunova and Dr. Andrei Seluanov. We look forward to future discoveries from this couple that can lead to life extension and cancer prevention for humans.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

  1. Van Meter M, Seluanov A, Gorbunova V. Forever young? Exploring the link between rapamycin, longevity and cancer. Cell Cycle. 2012 Dec 1;11(23):4296-7.
  2. Mao Z, Hine C, Tian X, et al. SIRT6 promotes DNA repair under stress by activating PARP1. Science. 2011 Jun 17;332(6036):1443-6.
  3. 3. Kanfi Y, Naiman S, Amir G, et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012 Feb 22;483(7388):218-21.
  4. Delaney MA, Nagy L, Kinsel MJ, Treuting PM. Spontaneous histologic lesions of the adult naked mole rat (Heterocephalus glaber): a retrospective survey of lesions in a zoo population. Vet Pathol. 2013 Jul;50(4):607-21.
  5. Azpurua J, Seluanov A. Long-lived cancer-resistant rodents as new model species for cancer research. Front Genet. 2013 Jan 9;3:319.
  6. Buffenstein R. The naked mole-rat: a new long-living model for human aging research. J Gerontol A Biol Sci Med Sci. 2005 Nov;60(11):1369-77.
  7. Keane M, Craig T, Alföldi J, et al. The naked mole rat genome resource: facilitating analyses of cancer and longevity-related adaptations. Bioinformatics. 2014 Aug 28.
  8. Tian X, Azpurua J, Hine C, et al. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature. 2013 Jul 18;499(7458):346-9.
  9. Chen WY, Abatangelo G. Functions of hyaluronan in wound repair. Wound Repair Regen. 1999 Mar-Apr;7(2):79-89.
  10. Seluanov A, Hine C, Azpurua J, et al. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat. Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19352-7.
  11. Azpurua J, Ke Z, Chen IX, et al. Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17350-5.
  12. Lee JW, Beebe K, Nangle LA, et al. Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature. 2006 Sep 7;443(7107):50-5.
  13. No authors listed. Breakthrough of the year 2013. Notable developments. Science. 2013 Dec 20;342(6165):1435-41.
  14. Ke Z, Vaidya A, Ascher J, Seluanov A, Gorbunova V. Novel husbandry techniques support survival of naked mole rat (Heterocephalus glaber) pups. J Am Assoc Lab Anim Sci. 2014 Jan;53(1):89-91.
  15. Gorbunova V, Seluanov A, Zhang Z, Gladyshev VN, Vijg J. Comparative genetics of longevity and cancer: insights from long-lived rodents. Nat Rev Genet. 2014 Aug;15(8):531-40.
  16. Gorbunova V, Hine C, Tian X, et al. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19392-6.