Sci. Aging Knowl. Environ., 5 May 2004
Vol. 2004, Issue 18, p. nf47
[DOI: 10.1126/sageke.2004.18.nf47]


If Telomeres Thrive, You Will Survive

Augmenting chromosome caps extends worm life span

Mitch Leslie

Much as cutting the biblical muscleman Samson's hair sapped his strength, trimming telomeres weakens a cell's power to survive. A new study of nematodes backs the idea that extending chromosome tips prolongs an animal's life span. The findings add a new twist by suggesting that lengthy telomeres stretch life not by affecting cell duplication, but by solidifying defenses against stress.

Telomeres, the protective tips of chromosomes, shrink every time a cell splits. Cultured cells with inadequate telomeres stop dividing, entering a state called replicative senescence that might hamper the older body's ability to mint replacement cells (see "More Than a Sum of Our Cells"). However, what role telomere erosion plays in animal or human aging remains uncertain, in part because many cells in adults never divide. Circumstantial evidence supports the notion that dwindling telomeres speed death. Depleting telomerase, the enzyme that restores chromosome caps in mice, hastens aging in the animals. And last year, researchers reported a higher death rate in elderly people with relatively short telomeres than in those with well-endowed telomeres (see "When Tips Disappear, the End Is Near").

To test telomeres' potential life-extending powers, developmental geneticist Junho Lee of Yonsei University in Seoul, South Korea, and colleagues experimented on a nematode strain in which all worms were almost identical genetically. The team stretched telomeres by outfitting some wrigglers with extra copies of a gene that encodes the protein HRP-1, which helps elongate the chromosome caps, possibly by helping telomerase into position. Nematodes with luxuriant chromosomes outlasted controls by about 20%. Like many long-lived creatures, worms with prodigious telomeres resisted heat especially well--they were almost twice as likely to survive 8 hours at 35° Celsius than were controls. However, the nematodes remained sensitive to the oxidant paraquat, suggesting that long telomeres don't guard against all stresses. Other work has shown that worms with mutations in the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway live extra-long, but only if they carry a functional copy of the daf-16 gene (see "Foundations of Longevity"). Lee's team discovered that telomeres require daf-16 to extend longevity, too. Worms with a faulty version of the gene survived the same amount of time regardless of their telomeres' condition.

"A lot of people thought that longer telomeres would do nothing at the organismal level," says Lee. Elongated telomeres boost longevity even though few cells in the adult worm divide, which suggests that the DNA segments affect aging through a mechanism other than replicative senescence, says Lee. But that mechanism remains mysterious.

The engineered nematodes' resilience is surprising, says cell biologist Peter Hornsby of the University of Texas Health Science Center in San Antonio, adding that the study is the first to link telomere length and survival in worms. No one has shown that lengthening telomeres in mammalian cells hikes stress resistance, but researchers should take a closer look to make sure they haven't missed the effect, he says. Probing that issue might reveal whether wearing our telomeres long will buy us extra time to show our strength.

May 5, 2004
  1. K. S. Joeng, E. J. Song, K.-J. Lee, J. Lee, Long lifespan in worms with long telomeric DNA. Nat. Gen., 2 May 2004 [e-pub ahead of print]. [Abstract/Full Text]
Citation: M. Leslie, If Telomeres Thrive, You Will Survive. Sci. Aging Knowl. Environ. 2004 (18), nf47 (2004).

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