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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-11-10
pubmed:abstractText
Ames dwarf mice and Snell dwarf mice lack growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH), live much longer than their normal siblings, and exhibit many symptoms of delayed aging. "Laron dwarf mice," produced by targeted disruption of the GH receptor/GH-binding protein gene (GHR-KO mice), are GH resistant and also live much longer than normal animals from the same line. Isolated GH deficiency in "little" mice is similarly associated with increased life span, provided that obesity is prevented by reducing fat content in the diet. Long-lived dwarf mice share many phenotypic characteristics with genetically normal (wild-type) animals subjected to prolonged caloric restriction (CR) but are not CR mimetics. We propose that mechanisms linking GH deficiency and GH resistance with delayed aging include reduced hepatic synthesis of insulin-like growth factor 1 (IGF-1), reduced secretion of insulin, increased hepatic sensitivity to insulin actions, reduced plasma glucose, reduced generation of reactive oxygen species, improved antioxidant defenses, increased resistance to oxidative stress, and reduced oxidative damage. The possible role of hypothyroidism, reduced body temperature, reduced adult body size, delayed puberty, and reduced fecundity in producing the long-lived phenotype of dwarf mice remains to be evaluated. An important role of IGF-1 and insulin in the control of mammalian longevity is consistent with the well-documented actions of homologous signaling pathways in invertebrates.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0070-2153
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
189-225
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Life extension in the dwarf mouse.
pubmed:affiliation
Geriatrics Research, Department of Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 62794, USA.
pubmed:publicationType
Journal Article, Review