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Growth Hormones and Aging: More isn't necessarily good.

John H. john at faraway.com
Fri Aug 1 16:49:36 EST 2003

An extract of the below article. Note the loss of IGF receptors, interesting
in relation to caloric restriction. AT the end of the article the author
qualifies the value of CR, advising that in very elderly animals increased
nutrition is beneficial.

John H>

Is growth hormone deficiency a beneficial adaptation to aging? Evidence from
experimental animals

Andrzej Bartke Trends in Endocrinology and Metabolism (July 17, 2003),
Geriatrics Research, Department of Medicine and Department of Physiology,
Southern Illinois University School of Medicine, 801 N. Rutledge,
Springfield, IL 62794-9628, USA

Mutant mice with reduced activity of the somatotropic axis age slower and
live longer

Mice homozygous for targeted disruption (knockout, KO) of the gene encoding
the GH receptor/GH-binding protein (Ghr-KO) are GH resistant, as
demonstrated by profound suppression of hepatic Igf1 expression, peripheral
IGF-I levels, somatic growth and adult body size [9]. These animals live
40-50% longer than do their normal siblings [3,10] , and show no decline of
cognitive function at the age at which their normal siblings are
significantly impaired [11]. Hypopituitary dwarf mice with primary
deficiency of GH, prolactin and thyroid-stimulating hormone exhibit a major
(40-65%) extension of life span, along with evidence of reduced immune,
collagen and cognitive aging [2,4,12] . Mutant little (lacking growth
hormone releasing hormone receptor, Ghrhrlit) mice with isolated GH
deficiency live longer than do normal mice if the obesity of the latter is
prevented by a low fat diet [4]. Strong support for the physiological role
of the somatotropic axis in the control of longevity was provided by the
recent report of a significant increase of longevity in female mice with
heterozygous KO of the gene encoding the IGF-I receptor [13]. It is
particularly interesting that a 50% reduction in the number of IGF-I
receptors in these animals prolongs life without a negative impact on
fertility, and with only a marginal reduction in adult body weight [13].
Consistent with the apparent role of GH actions in the control of aging, a
negative correlation of adult body size and longevity was demonstrated in
several studies of normal (i.e. not mutant, KO, or transgenic) mice [14,15]

johnYYYcoe at tpg.com.au

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