Study of 15 species shows larger rodents express less telomerase, perhaps as a cancer-fighting adaptation
By Trevor Stokes | December 7, 2006
An organism's body mass, rather than lifespan, correlates with the expression of telomerase, an enzyme that can lengthen cell life and increase cancer, according to new research in rodents published in the journal Aging Cell.
Telomerase rebuilds chromosomal ends that erode over time, and its activity gives cells longer life. Whereas short-lived mice express telomerase, long-lived humans shut down its expression in somatic cells.
"Mice express telomerase in all their cells, which helps them heal dramatically fast," said Vera Gorbunova, a researcher on aging at the University of Rochester who headed the study. "It would be nice to have that healing power, but the flip side of it is runaway cell reproduction -- cancer," she said.
The researchers hypothesized that telomerase repression, an adaptation in long-lived organisms, evolved to suppress tumors. To test this hypothesis, they investigated telomerase activity of 15 rodents from across the globe, ranging from tiny field mice to the 100-pound capybara from Brazil. Lifespans ranged from three years for the mice to 23 or more for common backyard squirrels.
No correlation between telomerase and longevity was observed, a result Gorbunova said she expected. Body mass correlated with telomerase activity across the 15 species. The capybara, nearly the size of an adult human, did not express telomerase, which the authors concluded was a mechanism to prevent cancer.
However, researchers aren't ready to throw away the lifespan hypothesis. "The product of both parameters [body mass and lifespan] could reflect the relationship better than the body mass alone," said Jirí Fajkus, telomere evolutionary biologist at Masaryk University, Czech Republic, who was not involved in the current study.
"Telomerase activity data should also be taken with reasonable caution since the activity measured in vitro in cell extracts need not necessarily reflect the real performance of telomerase inside cells," he added in an e-mail to The Scientist.
There is also the question of why telomere length, unlike telomerase, did not correlate with body mass. "It may be that telomerase activity is varying at the time of measurement, and hence no changes in immediate telomere length could be observed," suggested Barry Flanary, vice president of Phoenix Biomolecular Corporation, a biotech startup focused on developing telomerase-based therapies for age-related diseases.
Jerry Shay, a telomere biologist at the University of Texas Southwestern Medical Center at Dallas, pointed out that there is actually little supporting data for the lifespan hypothesis. "Nobody has done the critical study, which is a big survey [of telomere length and telomerase] that looks at all the animals in multiple lineages, up and down the whole evolutionary tree," he said.
Shay, who was not involved in the current study, told The Scientist that the telomerase-body mass connection is "very unlikely to be a general phenomenon across species...because there are exceptions." One example is the muntjac deer, which represses telomerase yet has a relatively short life and small body mass. Further, rabbit species generally do not repress telomerase though their lifespans range from short to long. Even Gorbunova noted an exception to the lifespan hypothesis in the common gray squirrel, which lives two decades yet expresses telomerase in great quantity.
Regardless of the exceptions, Gorbunova said the new findings raise another interesting question: How do animals far larger than humans, such as 250,000-pound whales, keep cancers at bay? "It may be that whales have a cancer suppressant that we've never considered," said Gorbunova. "I'd like to find out what kind of telomerase expression they have, and find out what else they use to combat cancer."
Links within this article:
A. Seluanov et al. "Telomerase Activity Coevolves with Body Mass not Lifespan," Aging Cell Dec. 6, 2006
P. Smaglik, "Turning to Telomerase: As Antisense Strategies Emerge, Basic Questions Persist," The Scientist, Jan. 18, 1999
G. Flores, "New function for telomerase?" The Scientist, Aug. 18, 2005
J. Yajnik, "Blackburn, Greider, Szostak share Lasker," The Scientist, Sept. 18, 2006
J. Weitzman, "Rb and telomeres," The Scientist, Oct. 16, 2002
Phoenix Biomolecular Corporation
J. Shay and W.E. Wright, "Does Telomerase Moonlight?" The Scientist, Feb. 28, 2005