Sci. Aging Knowl. Environ., 4 June 2003
Stress-resistant cells come in small packages
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/sageke;2003/22/nw79
Key Words: insulin-related signaling heavy metals heat shock WST-1
The mellow surf bum might outlast the type A executive because she lets stress bounce off her. Similarly, long-lived dwarf mice might endure because their cells resist numerous affronts, according to new work. The results provide a possible explanation for why the petite animals persist and also bolster the suspected connection between longevity and stress resistance.
Several pint-sized mouse strains live unusually long. For instance, Snell dwarves meet their cheesemaker 50% later than do normal mice. The animals harbor a mutation that blocks pituitary maturation and, as a consequence, hinders the production of several hormones that are crucial for growth. For example, amounts of insulin-like growth factor-1 (IGF-1) are tiny. Crippling an IGF-1-like pathway in worms and flies extends life span. Together, the observations suggest that different organisms share hormonal circuits that govern longevity (see "Growing Old Together"). The long-lived flies and worms with glitches in the IGF-1-like pathway shrug off stress and pump out excess repair proteins (see Johnson Review). Some data hint that persistent rodents resist adversity (see "One for All"), but researchers haven't sealed the connection in the furry beasts. Murakami and colleagues wondered whether Snell dwarf mice boast a particularly strong stress response.
To address that question, the researchers grew skin cells from the animals in culture. Then they bombarded the cells with a variety of noxious treatments: heat, ultraviolet radiation, the herbicide paraquat, hydrogen peroxide, and the poisonous metal cadmium. Fifty percent more dwarf than normal cells survived paraquat or UV treatment; more than twice as many survived heat, peroxide, or cadmium treatment. Cells from two lines of mice--each carrying the Snell mutation--showed heightened fortitude, implying that the Snell mutation itself is responsible. The authors plan to hunt for genes with altered activity in the dwarves; those genes could lead them to the biochemical pathways by which these mice fight off life's assaults.
"The results are really striking," says physiologist Andrzej Bartke of Southern Illinois University School of Medicine in Springfield. Previous studies have challenged cells or animals with only one type of treatment, he says. "The main strength [of the new study] is that they tested multiple stresses," so the researchers know that they're studying general hardiness, not just an improved response to one particular insult. The results support the idea that longevity and stress resistance go hand in hand, but proving that link is difficult, he adds. In unpublished work from Bartke's group, dwarf mice of a different strain outlasted their normal counterparts when dosed with paraquat. But such experiments are fraught with problems, says Bartke. Mild doses of toxins can promote longevity (see "Stress for Success"), so experiments must stress animals to a degree that is "not horrendous but out of the range that's beneficial." That amount is difficult to determine. Nevertheless, the results fortify the notion that honed stress repellents might mean more time to catch some waves.
--R. John Davenport
June 4, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150