Sci. Aging Knowl. Environ., 9 February 2005
Dosed to Death
Thyroid hormone treatments shorten mouse life span
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2005/6/nf11
Extra-small mice enjoy a supersized life span, and new results help clarify the hormone changes that are responsible. A dearth of thyroid hormone seems to play a crucial role, the work reveals. The study also indicates that animals don't have to be little to persist.
Rodents with mutations that stunt the pituitary gland are miniature and live long (see Snell and Ames dwarf mice). They carry unusually small amounts of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1). Many researchers have focused on these molecules to explain the rodents' extraordinary life spans, because other studies have connected glitches in the hormone pathways to slowed aging. But the dwarfs harbor other deficiencies, such as a scarcity of metabolism-boosting thyroid hormone, and researchers haven't nailed down which flaws are responsible for the exceptional longevity.
To investigate the role of thyroid hormone, pathologist Richard Miller of the University of Michigan, Ann Arbor, and colleagues injected Snell dwarf mice with thyroid and growth hormones from the ages of 4 weeks to 15 weeks--the animals' puberty and adolescence. After the treatment, some of these creatures also received thyroid hormone in their food until they died. The researchers compared rodents that underwent these two treatments to untreated dwarfs and to genetically normal animals. Animals that received only the 11-week treatment grew about 50% larger than did untreated dwarfs but lived as long. Although the rodents remained undersized, the finding suggests that animals don't have to be minuscule to gain time, says Miller. In addition, thyroid hormone injections restored fertility in Snell dwarfs.
Rodents dosed with thyroid hormone throughout their lives also bulked up, but they died sooner than did untreated dwarfs. Whether the treatment accelerated aging or was toxic isn't certain, says Miller, but the finding supports the idea that scant thyroid hormone contributes to dwarfs' prolonged survival. Moreover, the results suggest that adulthood is the crucial period for this effect, because animals that received thyroid hormone only until 15 weeks of age still lived long. Additional experiments revealed that dwarfs suffer fewer cataracts and less kidney damage than normal.
"The data indicate that just making [dwarf mice] bigger doesn't do anything to their longevity," says physiologist Andrzej Bartke of Southern Illinois University School of Medicine in Springfield. "That's important" because previous studies have suggested a link between smaller body size and longer life (see "The Shrimps Shall Inherit the Earth"). The observations of reduced tissue deterioration add to the growing pile of evidence that dwarfs age more slowly rather than resist particular diseases, he says. The study suggests that thyroid hormone makes an important contribution to determining longevity and "that GH and IGF-1 may not have as prominent a role as previously thought," says endocrinologist William Sonntag of Wake Forest University in Winston-Salem, North Carolina.
Many older people suffer from flagging thyroids, and doctors typically prescribe supplementary thyroid hormone. But the study calls into question whether they should receive extra amounts, says gerontologist Rudi Westendorp of the University of Leiden in the Netherlands (see "Playing With Fire"). The results mesh with his findings, published in November 2004 in The Journal of the American Medical Association, that octogenarians with lower thyroid activity lived longer than those with higher activity. Moreover, low thyroid activity didn't provoke depression or memory problems, side effects that doctors have long associated with the gland's malfunction. Further studies should help scientists discern whether downsizing the thyroid is crucial for keeping life span turned up to the max.
February 9, 2005
Science of Aging Knowledge Environment. ISSN 1539-6150