Endocrine Function in Long Living Mouse Mutants: The Other Side of the
Coin
A. Bartke
Department of Physiology
Southern Illinois University
Carbondale, IL 62901
Growth hormone (GH) release normally declines with age and GH
replacement can reduce
or reverse some of the age-related changes in body composition. In the
context of the widely
advertised "anti-aging" actions of GH, it is interesting to consider
alterations in the somatotropic axis of long-lived mutant and knock-out
(KO) mice. Ames dwarf and Snell
dwarf mice have congenital primary deficiency of GH, prolactin(PRL) and
thyrostropin, and
outlive their normal siblings by as much as 60%. GH receptor KO
(GHR-KO) mice are GH
resistant and live nearly 50% longer than normal (+/+ or +/-) mice from
the same line.
Physiological characteristics shared by dwarf and GHR-KO mice include
profound
suppression of peripheral IGF-I levels, reduced postnatal growth,
diminutive adult body size,
reduction in plasma insulin and glucose levels, and increased
responsiveness to exogenous
insulin. Corticosterone levels are normal in females and somewhat
elevated in males. Dwarf
females are sterile due to PRL deficiency, while both sexes of GHR-KO
mice are fertile.
Effects of mouse "longevity genes" on endocrine function suggest that
normal actions of GH,
including stimulation of postnatal growth are associated with major
"costs" in terms of aging
and life expectancy. Reduced responsiveness to insulin emerges as one
of potential
mechanism of GH action on aging and longevity. There are indications
that similar
relationships may exist in the human.
Problems or questions regarding this site should be directed to
webmaster@americanaging.org